BIOL 4803 Lecture Notes - Lecture 1: Blind Experiment, Medical Nutrition Therapy, Scientific Control

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27 Aug 2018

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Discuss factors that influence your food choices. Differentiate between six categories of essential nutrients found in food and in the body. Understand importance of well-balanced diet in meeting your daily nutrient needs. Discuss the current nutritional state of the american diet. Understand the scientific method that is involved in nutrition research and identify reliable sources of nutrition information. We choose foods for many other reasons beyond basic need to obtain nutrients: metabolism: taste and culture, social reasons and trends, cost, time, and convenience, habits and emotions. Food choices: nutrition knowledge, trends, taste, habits, emotions, nutrients, time, cost, convenience, culture, advertising, social reasons. Nutrition ~ science that studies how nutrients and compounds in foods nourish and affect body functions and health: good nutrition plays role in reducing risk of many chronic diseases and conditions, including heart disease, cancer, and stroke. Carbohydrates supply glucose, a major energy source. Fats are another major fuel source; cushion organs; insulate body to maintain body temperature.

Related Questions

Background: In this assignment, you willinvestigate the chemical composition of the foods we eat as ourbodies break down food by the digestive process.

The USDA Nutrient Data Laboratory has posted a resourcethrough which you can investigate the chemical composition offoods. Go to the USDA Lab Link at USDA Nutrient DataLaboratory: http://ndb.nal.usda.gov/

Instructions

Type in a keyword, then select a food group using the drop-downarrow, then click "submit."
This pulls up a menu with lots of choices.
Choose one food choice, then click "submit"
Next choose a portion size, then click "submit"
This will bring up the nutritional informationneeded to complete the assignment.

Example:

Keyword: Apple
Select Food Group: Fruits and FruitJuice
Apples, raw, with skin.
One medium

Assignmentdetails:

A. Nutrition: Analyze the nutritionalcomponents of the food you select; and in your own words, answerthe following questions using the USDA Nutrient Data Laboratory Website as listed in the unit Web resources:

What was the food and portion size you chose?
Describe its composition in terms of carbohydrates, lipids, andproteins.
How many calories are in your food item? (Found in the Databaseas Energy Ã¢â¬â kcal)
List some of the most common vitamins and minerals in this fooditem.
Are there other important nutritional components of this fooditem? If so, list these. If not, say so.

B. Water:

How much of your food item is water?
Provide one reason why water is important for life. Toadequately answer this question, it will be necessary to explain areason for waterÃ¢â¬â¢s importance based upon its chemical and /orphysical properties.

C. Biological Molecule:

State the most abundant category of biological molecule in yourfood: carbohydrates, lipids, or proteins.
Describe the structure of this type of molecule, and itsprimary function(s). This section will not be a one sentence answer.In order to adequately Ã¢â¬ÅdescribeÃ¢â¬ an entire category ofbiological molecules, you will need to briefly review their basicmolecular structures and functions.

D. Recommendation:

After identifying the nutritional components, discuss WHY youwould or would not recommend this food item as part of a healthy,nutritious diet. Be sure to use references and guidelines such asthe Food Pyramid and Recommended Daily Allowances to support yourrecommendations.

goldrabbit184

Question 2

The DSM-IV describes an "Eating Disorder Not OtherwiseSpecified" as:

self-starvation that leads to severe nutrient deficiencies

compulsive eating disorder

a variety of atypical eating behaviors used to maintain or lowerbody weight

recurrent episodes of extreme overeating followed byself-induced vomiting

Question 3

The nutrition paradox refers to:

coexistance of underweight and obesity in the same region

too mucn vitamin A in foods rich in vitamin C

poor countries that have excessive rates of obesity

obese children from nonobese parents

Question 4

Which of the following represents a nutrition transition?

decreased reliance on carbohydrates

increased consumption of sugar

increased availibility of maize over corn

lower-fat subsistence crops

Question 5

Which of the following is NOT part of the GOBI initiative?

breast-feeding

obesity control

immunization

growth monitoring

Question 6

Which of the following is a response to the drawbacks of theGreen Revolution?

WIC

high yield varities of grains

sustainable agriculture

biotechnology

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Question 70.5 pts

Worldwide, the major cause of undernutrition is:

unequal distribution of food

diseases (like AIDS)

poor farming practices

overpopulation

Question 8

Which agency monitors all confirmed causes of food-borneillness?

EPA

FDA

CDC

USDA

Question 9

In which of the following environments does Clostridiumbotulinum flourish?

acidic

alkaline

<40 degrees F

> 140 degrees F

Question 10

Which of the following is an example of food intoxication?

Norwalk virus

Salmonella

hepatitis A

Clostridium botulinum

Question 11

All of the following describe characteristics of the femaleathlete triad EXCEPT

menstrual dysfunction

disordered eating

hypertension

osteoporosis

Question 12

Impulsive, low self-esteem, seeks attention, extroverted, anderratic describe personality traits of:

bulemia nervosa

binge-eating disorder

obesity

anorexia nervosa

Question 13

Obsessive-compulsive, perfectionism, socially inhibited,compliant, and emotionally restrained describe personality traiatsof

binge-eating disorder

anorexia nervosa

bulimia nervosa

obesity

Question 14

The Institute of Medicine recommends a minimum of ________minutes of physical activity each day for adults.

Question 15

Regular exercise reduces the risk of type 2 diabetes by all butwhich of the following?

decreases the cellular uptake of blood glucose

delays the onset of complications of type 2 diabetes

increases control of blood glucose

enhances the action of insulin

Question 16

What is meant by the overload principle?

stretching a muscle group beyond the joint's healthy range ofmotion

improving fitness by placing extra physical demand on thebody

complete depletion of the body's glycogen

subjecting the body to inappropriately high stress

Question 17

The acronym FIT stands for:

fatigue, intensity, and training.

flexibility, increase, and training.

fitness, increase, and time.

frequency, intensity, and time.

Question 18

To achieve cardiorespiratory fitness it is recommended thattraining should occur ________.

3-5 days a week

daily

more than 5 days a week

2-3 days a week

Question 19

To achieve and maintain physical fitness, exercise intensityshould be ________ of the maximal heart rate.

35-50%

15-25%

25-30%

50-80%

Question 20

In which of the following types of exercise would CP (creatinephosphate) be an important source of energy?

biking up a mountain

sprinting in the 100-meter race

running a 10-kilometer road race

playing in a football game

Question 21

Which is NOT an advantage of aerobic metabolism over anaerobicmetabolism?

Much more energy is produced for every fuel molecule.

Aerobic metabolism acts more quickly.

Harmful metabolites do not accumulate as quickly.

A greater fuel supply is available.

Question 22

An unwanted effect of an overly vigorous warm-up is:

increased muscle temperature.

glycogen depletion.

increased body temperature.

reduced stress levels.

Question 23

Each day Bill power-walks for 45 minutes. Which fuel source(s)provide(s) energy during this activity?

amino acids

glucose

fatty acids

fatty acids and glucose

Question 24

The main disadvantage of using fat as a fuel is:

the body's limited storage capability.

its low energy density.

its slow metabolic breakdown.

the limitation of anaerobic metabolism.

Question 25

Joseph plays basketball for his high school team and he isconcerned that he is not consuming enough kilocalories to supporthis activity. Which of the following would be the best indicatorthat he is not consuming adequate kilocalories?

His hemoglobin is low.

His blood glucose levels are low.

His performance has been impaired.

He is losing weight.

Question 26

Rachel is a gymnast who trains 2 hours/day on average. Shesupports her daily activity by consuming 2,500 kilocalories perday. How many kilocalories should she be consuming fromcarbohydrate sources?

1,500-1,625 kilocalories

1,125-1,300 kilocalories

1,300-1,500 kilocalories

1,625-1,750 kilocalories

Question 27

The best time to replenish glycogen stores is:

the day after exercising.

a few hours before exercising.

the day before exercising.

right after exercising.

Question 28

In which of the following events would carbohydrate loading bethe most beneficial?

cross country skiing

baseball game

weight lifting

100-yard dash

Question 29

Osteoporosis, eating disorders, dehydration, and heat illnessare all possible consequences of:

the Zone diet.

carbohydrate loading.

inadequate dietary intake.

overtraining.

Question 30

Which of the following is the most potentially harmful?

heat syncope

heatstroke

heat cramps

heat exhaustion

Question 31

Which of the following athletes would be LEAST likely to developiron deficiency anemia?

a female marathon runner

a male basketball player who is a vegan

a female gymnast

a male distance swimmer

Question 32

Amenorrhea, sometimes seen in female athletes, is:

the onset of menstruation.

osteoporosis.

the loss of the menstrual cycle.

frequent diarrhea.

Question 33

Some athletes believe that caffeine can enhance athleticperformance because it has been shown to:

increase the transport of amino acids to exercising muscle.

increase muscle flexibility and strength.

increase the use of fatty acids as a fuel source.

regenerate ATP for energy.

Question 34

Which of the following ergogenic aids has been shown to enhanceshort-term exercise and resistance training?

chromium picolinate

creatine

carnatine

ephedrine

Question 35

Consuming processed foods as opposed to whole foods decreasesthe risk of contracting a food-borne illness.

True

False

Question 36

Regular physical activity can increase HDL-cholesterol.

True

False

Question 37

Nearly 1 in 6 American adults reports getting no physicalactivity at all.

True

False

Question 38

Lactic acid is a by-product of high-intensity exercise.

True

False

Question 39

Training can enhance the ability to store glycogen.

True

False

Question 40

The primary fuel source utilized in both anaerobic and aerobicexercise is protein (amino acids).

True

False

Question 41

Studies suggest that athletes need to consume more than 2grams/kg of protein each day to maintain muscle strength.

True

False

Question 420.5 pts

Refigerating or freezing foods will kill any bacteria present inthe food.

True

False

Question 43

Most athletes do not consume enough protein to support theiradded physical activity.

True

False

Question 44

Thirst is a very reliable indicator of dehydration.

True

False

Summarize the following reading (Nutrient (zinc and vitamin E)-gene interactions related to inflammatory and antioxidant response in aging and inflammation) and it should be at least one paragraph (100-200 words) and include the following information:

* Main point of the reading

* Describe how the health deviations you read about alter normal physiology.

* Provide your key take away from the reading. This could be something that made you pause, changed your thinking, supported your thinking, or made you question something.

INTRODUCTION Aging is an inevitable biological process that is accompanied by gradual and spontaneous biochemical and physiological changes including increased susceptibility to diseases, adverse environmental conditions, and loss of mobility and agility. Alterations in neuroendocrine-immune interactions as well as in antioxidant capacity also play a fundamental role in aging. The inability of an organism to remodel these changes may lead to the appearance of some degenerative age-related diseases. As a result, the remodeling theory of aging has been proposed (1). Various nutritional factors are directly linked to these phenomena, as, for instance, in restoring the neuroendocrine-immune network, metabolic harmony, and the capacity to respond to oxidative stress (2). Approximately 40 micro nutrients (vitamins, essential minerals, and other compounds required in small amounts for normal metabolism) have been reported as essential components in the diet (3). The dietary intake of essential macro nutrients and micronutrients is usually inadequate in the elderly (4). Several causes contribute to this gap. First of all, the poor socio-economic conditions in which a large part of the older population live may lead to a consumption of inexpensive foods deficient in micronutrients, such as carbohydrates (5). The gap is worsened by the loss of appetite, lack of teeth, intestinal malabsorption, and decreased requirements for energy that lead finally to frailty, disability, and mortality (6). Some authors have reported that the deficiency of macro nutrients and micronutrients in aging is strictly related to global impairments of immune functions, metabolic harmony, and antioxidant defense by external noxae with subsequent appearance of age-related diseases (7). Indeed, many micronutrients contribute directly or indirectly to the biological activity of some antioxidant enzymes (e.g., SOD, GPx, and catalase) (8), to the efficiency of the immune system (9), and to the maintenance of metabolic function especially in preventing mitochondrial decay (4). In this last context, feeding studies in older rats have shown that mitochondrial metabolites and antioxidants protect neuronal cells from neurotoxin- and oxidant-induced toxicity and oxidative damage, delay the normal senescence of human diploid fibroblasts, and inhibit the oxidant-induced acceleration of senescence (10). With advancing age, increased oxidative damage to proteins and lipid membranes, particularly in mitochondria, causes a deformation of the structure of enzymes, with a consequent decrease in enzyme activity as well as substrate binding affinity for their substrates. An increased level of the substrate by micro nutrients restores the speed of the reaction as well as mitochondrial function, thus delaying mitochondrial decay and aging (10, 11). In contrast, recent longitudinal studies of dietary daily intake in human nonagenarians and centenarians (successful aging) have shown that an adequate consumption of micronutrients and macronutrients, as well as a satisfactory content of some trace elements within the cells, leads to good performance in several immune functions, metabolic compensation, and preservation of antioxidant activity (12, 13). In this context, polyunsaturated fatty acids, highly sensitive to reactive oxygen species, decrease in liver mitochondria from human centenarians, a feature acquired during evolution as a protective mechanism to favor longevity (14). Therefore, nutritional factors may play a pivotal role for healthy aging and longevity. However, the effects of the nutritional factors are strongly influenced by genetic factors, in particular by the genes involved in inflammatory/immune responses. Proinflammatory cytokines such as IL-1, IL-6, and TNF-Î±; the antiinflammatory cytokine IL-10; the HSP70 chaperones; and the regulators of trace element homeostasis, metallothioneins (MTs), seem particularly relevant, taking into account that the same genes are involved in the susceptibility to major geriatric disease/disorders such as diabetes, osteoporosis, osteoarthritis, dementia, cardiovascular diseases, and infections (15, 16). Indeed this reemphasizes that up to 25% of the variation in human life span is heritable (17); the rest is due to environmental and lifestyle factors, which impact the aging process, contributing as such to a large interindividual variability. Therefore, one current challenge is to understand how the interaction between genetic factors and nutrients may influence aging and longevity, in view of the high impact on gene expression, protein production, and epigenetic mechanisms implicated in regulating the life span (18). Some dietary patterns with likely different impacts on longterm disease occurrence and survival have been identified. In this context, strong evidence for a beneficial effect of higher conformity with the Mediterranean dietary pattern on causes of death, including those of cardiovascular diseases and cancer, has been reported (19). Anyway, it is also commonly accepted that the complex interactions of multiple polymorphisms play a key role in how individuals may respond to dietary interventions (20). For each nutrient, there is a window of intake between the recommended dietary allowance (RDA), which is defined as the dietary intake sufficient to meet the requirements of 97% of healthy individuals in a particular stage of life and sex group, and the tolerable upper limit (UL), which is the highest nutrient intake that can be achieved without incurring a risk of adverse health effects for most individuals in the general population (21). Although worldwide research on genetic variations that require a different RDA or UL is still in progress, several genes and alleles have been suggested to affect nutrient utilization, including genes involved in the metabolism of folate and vitamin B12 (22), vitamin E (23), lipids (24), iron (25), and zinc (26). In this last case, it is important to note that the RDA (11 mg/day for men, and 8 mg/day for women) and UL (40 mg/day for adults) for zinc are very close (Food and Nutrition Board and Institute of Medicine, 2001). Without excluding the beneficial effects of all of these nutrients for healthy aging and longevity (27), but taking into account the pivotal role played by zinc and vitamin E in fighting oxidative stress in aging and in some age-related diseases, such as atherosclerosis (23), we herein report the studies carried out on the interrelationships between zinc and some genes related to the inflammatory/immune response (such as MT and IL-6), as well as the interactions between vitamin E and the gene expressions related to inflammation. Clinical trials of zinc and vitamin E are also reported for their possible beneficial effects on longevity or in preventing the initiation and progression of cardiovascular diseases.

ZINC-MT GENE INTERACTION MTs MTs are essential to intracellular zinc homeostasis by sequestration and release of the metal when it occurs and thereby controlling available free zinc ions (28). The cysteine sulfur ligands in the cluster structure of MT can be reduced (zinc sequestration) or oxidized (zinc release), thus with concomitant changes in the relative amount of bound and free zinc (29). MTs are genetically polymorphous protein families with subfamilies, subgroups, and various isoforms. Humans possess genes for 4 subfamilies (encoded by at least 10 functional MT genes), all located on chromosome 16: the brainspecific MT3, the squamous epitheliumâspecific MT4, and the ubiquitous MT1 and MT2 (30). One of the first functions of MT1 and MT2 is to regulate zinc homeostasis and to limit oxidative damage within the cells (28). Following an injurious stimulus, such as a transient inflammation, the subsequent oxidative stress induces the release of zinc from MT via nitric oxide (NO), to promote the activity and expression of antioxidant enzymes, including MT itself, thus reducing the oxidative damage and the consequences of the injurious stimulus (31). However, the increased expression of proinflammatory cytokines occurring in aging, leads to increased expression of MTs, which in turn sequester considerable amounts of zinc, making it less available for an efficient immune response (32). If, on the one hand, the reduced zinc ion availability in old age might indicate an excessive sequestration of zinc ions by MTs, on the other, consideration of recent findings on oxidative modification of MTs leading to their loss of function suggests also a mechanism whereby these proteins can also lose their ability to buffer the intracellular free zinc concentration (33). In this case, MTs would be unable either to bind or to consequently release zinc in response to stressors. However, it is still unclear if dysfunctional MTs can be considered a typical alteration associated with specific disease/disorders, such as hyperhomocysteinemia and type 2 diabetes, or if they are a common feature of aging. Anyway, as a consequence of the altered zinc metabolism, a large number of genes that act as zinc sensors and transcriptional activators and/or repressors are also altered in aging (34). This may have a deep impact on the regulation of zincdependent transcription factors, because they not only regulate âzinc sensitiveâ genes but also control their own transcription through positive autoregulatory mechanisms (35). Taking into account that healthy centenarians display a low MT expression and satisfactory zinc ion availability despite increases in proinflammatory cytokines (IL-6, TNF-Î±) (36), it may be suggested that this feature reflects the existence of compensatory phenomena able to counteract the effects of inflammation in these exceptional individuals. Moreover, these data suggest that a preservation of zinc homeostasis is an important feature of healthy centenarians. Therefore, the role played by the zinc-gene interaction is pivotal to successful aging and, at the same time, to escape from some age-related diseases. Since, the persistence of inflammatory stimuli over time represents the biological background favoring susceptibility to age-related diseases/ disabilities, the absence of specific ârobustâ gene variants and/or the presence of specific âfrailâ gene variants might predict, on the one hand, longevity, and on the other, the predisposition to the appearance of the more common age-related diseases, such as infections and cardiovascular diseases. In this context, it has to be considered that the genes selected, because they confer a reproductive advantage early in life, may have dangerous effects in the postreproductive period. In fact, negative selection against these harmful effects fails due to the decline of natural selection with age. This fact means that one gene that is âfavorableâ in young/adult age may be âdisadvantageousâ in aging (the antagonistic pleiotropy theory of ageing (37)). Following this perspective, the beneficial effect of inflammation, via an optimal MFT-1-MT-zinc-gene interaction, in young and adult age may become detrimental in old age (32). The recent discovery of novel polymorphisms of MT2A and MT1A supports this assumption. Indeed, older subjects carrying the AA genotype for the MT2A polymorphism display low zinc ion bioavailability, chronic inflammation by high IL-6 and altered lipid assessments, with subsequent elevated risk for atherosclerosis and type 2 diabetes (38). By contrast, a polymorphism corresponding to an A/T (asparagine/ threonine) transition at the +647 nt position in the MT1A-coding region is the most often involved in female longevity (39). Such allelic variants may be very useful tools to screen older subjects at risk for zinc deficiency on a genetic basis, taking into account that the actual methodological procedures to test âzinc statusâ are often misleading and that laboratory investigations to assay zinc ion bioavailability are scarcely reproducible and poorly applicable to clinical practice (40). In this context, a novel reproducible system for testing intracellular zinc ion bioavailability has been developed using a zinc fluorescent probe (Zynpir-1) associated with MT values, with both tests representing valid methods to detect the intracellular zinc status (41).

ZINCâINTERLEUKIN-6 GENE INTERACTION Interleukin-6 (IL-6) is a pleiotropic cytokine capable of regulating proliferation, differentiation, and activity of a variety of cell types, and it plays a pivotal role in immune response. In particular, the most important function of IL-6 is most likely as a mediator of acute phase inflammatory responses. These include the balance of the proinflammatory/antiinflammatory pathways, lymphocyte activation, and hepatocellular stimulation of acute phase protein synthesis (42). Studies of the effects of aging on inflammatory response show IL-6 to be an important âcytokine for gerontologistsâ. Recent evidence has shown that abnormally increased concentrations of IL-6 are reliable markers for functional disability and predictors of disability and mortality among the elderly (43). Moreover, IL-6 dysregulation is involved in age-related inflammatory diseases, such as cancer, lymphoma, cardiovascular diseases, osteoporosis, Alzheimerâs disease, diabetes and atherosclerosis (44). The human IL-6 gene is located on chromosome band 7p21 and consists of 5 exons and 4 introns (45). Genetic studies have identified 4 polymorphisms in the Lattanzio et al 121 promoter region of the IL-6 gene (-597G/A, -572G/C, - 373A/T, -174G/C) that have a significant effect on IL-6 expression in an in vitro system (46). A variable number of tandem repeat (VNTR) polymorphisms were found in the 3â flanking region of the IL-6 gene (C allele) (47). In humans, a polymorphism in the IL-6 promoter (A/C polymorphism at position -174) altered IL-6 gene transcription rates in vitro (48) and IL-6 levels in vivo (49). In this last paper, people carrying CC or GC genotypes are defined as C+, while those carrying GG genotypes are indicated as C-. It has been suggested that IL-6 -174G/C locus variability is capable of modulating, on the one hand, individual susceptibility to common causes of morbidity and mortality among elderly, while, on the other hand, it may play a crucial role in longevity (50). Therefore, the genetic variations of this locus of IL-6 gene are fundamental in the elderly population to better understand the intrinsic causes of the longevity. The association of these genetic variations to the possible, different immune responses is an attractive focus in elucidating the molecular mechanisms involved in immunosenescence. The genetic variations of the IL-6 -174G/C locus have been extensively studied by different groups with, however, contradictory data. BonafÃ¨ et al (51) studied IL-6 promoter genetic variability at the -174C/G locus and its effect on IL-6 levels in 700 Italians aged 60 to 110 years, including 323 centenarians. Individuals who are genetically predisposed to produce high levels of IL-6 during aging â i.e., C- men (GG genotype) â at the IL-6 -174C/G locus are disadvantaged for longevity. On the other hand, the capability of C+ individuals (CC and CG genotypes) to produce low levels of IL-6 throughout their life span appears to be beneficial for longevity, at least in men. Women have, conversely, high IL-6 serum levels later in life with respect to men, independently of -174C/G locus polymorphism (51). The inhibitory tone of estrogens on IL-6 gene expression could explain the sex-based difference (52), assuming that its long-term effects last until the extreme limits of the human life span. The major production of IL-6 in C- subjects for their whole life, including centenarians, has also been confirmed by other in vivo longitudinal studies (53). A more recent study in older and nonagenarian subjects has confirmed that IL-6 production is higher in C- carriers and that these subjects are prone to contract one of the more common age-related inflammatory pathologies such as atherosclerosis (54). Interestingly, in this last study, C- older and nonagenarian subjects also display impaired innate immune response (NK cell cytotoxicity) coupled with increased MT, zinc deficiency, and low zinc ion availability, in comparison with C+ carriers (54). A functional effect of the IL-6 -174G/C locus on MT expression and zinc-regulated genes has also been confirmed recently by targeted studies with in vitro and in vivo zinc supplementation (55, 56). These findings clearly suggest that the genetic variations of the IL-6 -174G/C locus play a key role in longevity also at a functional level, and confirm the existence of a higher number of C+ centenarians than Câ ones as previously found by BonafÃ¨ et al (51). In this context, an intriguing point is the low expression of the signal-transducing component (gp130) of the IL-6 receptor in centenarians, in comparison with the elderly, despite high circulating levels of IL-6 (57), which in turn may be inactive in centenarians (36). Therefore, inflammatory status is not so detrimental in very old age, as, in contrast, occurs in normal aging. However, the discrepancies among all of the genetic studies on the variations of the IL-6 -174G/C locus in relation to longevity in the elderly means that the subject is still unclear. Ethnic, lifestyle, and cultural differences among these populations could also play a role, as well as other undefined factors. Large-scale studies at the European level in many different ethnic populations are needed to clarify this important topic. For this reason, ZINCAGE project (www.zincage.org) has been developed, and the clarification of this point has been one of is tasks. The determination of the genetic variations of the IL-6 - 174G/C locus associated with a dietary assessment or with a comprehensive evaluation of zinc status has been reported as an useful strategy to identify older subjects who can benefit from zinc supplementation without health risks (see next paragraph).

ZINC SUPPLEMENTATION IN THE ELDERLY ON THE BASIS OF GENETIC BACKGROUND One possible cause of the discrepancies existing in the literature on the effect of zinc supplementation upon immune response and antioxidant performance in the elderly (see review in (58)) may be the choice of older subjects who effectively need zinc supplementation in strict relationship with dietary habits and inflammatory status. This fact is supported by the discovery that older subjects carrying GG genotypes (i.e., C- carriers) in the IL-6 -174G/C locus display increased IL-6 production, low intracellular zinc ion availability, and impaired innate immune responses coupled with enhanced MT (56). By contrast, older subjects carrying the GC and CC genotypes (C+ carriers) in the same IL-6 -174 locus display satisfactory intracellular zinc as well as innate immune responses. But, the more intriguing finding is that males carriers of the C+ allele are more likely to reach centenarian age than C- carriers. Therefore, older C- subjects are more likely to benefit from zinc supplementation than older C+ carriers. The distribution of the IL-6 -174 genotype is very different among the various European countries, with large differences between northern and southern European countries (58). Zinc supplementation in older C- subjects restores NK cell cytotoxicity to values present in older C+ carriers and considerably improves both zinc status, assessed by the percentage increment of granulocyte Zn (56), and stress response, assessed by the percentage increment of clusterin (CLU) expression and MT protein (58). When the genetic variations for the IL-6 polymorphism are also associated with the genetic variations of MT1A in position +647, the plasma zinc deficiency and the altered immune response are more evident (58), suggesting that the genetic variations of IL-6 and MT1A would be very useful tools for the choice of older people who effectively need zinc supplementation. These results open the hypothesis that the daily requirement for zinc might be different in elderly with a different genetic background. Such a role played by genetic background on the beneficial effects of zinc supplementation is also evident in the better control of proinflammatory cytokine and chemokine production (59), as well as in reducing the expression of genes related to inflammatory status, such as IL-1 and its receptor (55). A very intriguing point is also the beneficial effect of zinc supplementation in the cognitive performance of older individuals selected on the basis of IL-6 polymorphism (60). In any case, from a microarray analysis in vitro, zinc at a dose of 50 mM down-regulates the gene expression of proinflammatory cytokines (Fig. 1), strengthening its antiinflammatory role (56, 58).

Fig. 1 - In vitro zinc treatment (50 ÂµM) down-regulates proinflammatory cytokine expression (custom array) when refereed to the value 1 (baseline control) in human peripheral blood mononuclear cells from young adult donors. The red square represents the proinflammatory cytokines (IL-6, IL-1, and TNF pathways). Data redrawn from the Zincage Project (www.zincage.org) (61).

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BIOL 4803 Lecture Notes - Lecture 1: Blind Experiment, Medical Nutrition Therapy, Scientific Control

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