key: cord-0042375-psybu9ie authors: Jackson, Ron S. title: Wine, Health, and Food date: 2007-09-02 journal: Wine Science DOI: 10.1016/b978-012379062-0/50013-5 sha: 9d72c7fb7c5fdf6229930abb904b5c6c1ce7cfd6 doc_id: 42375 cord_uid: psybu9ie nan and Food The contrasting social and antisocial effects of moderate versus excessive alcohol consumption must have become evident almost as soon as wine was discovered. Time has only compounded the multifaceted nature of this Dr. Jekyll-Mr. Hyde effect of alcohol on human welfare. It is clear that excessive alcohol consumption, both acute and chronic, can have devastating effects on the physical and mental well-being of individuals. Excessive ethanol consumption can cause cirrhosis of the liver, increase the likelihood of hypertension and stroke, favor the development of breast and digestive tract cancers, and augment the potential for fetal alcohol syndrome. Many of these effects may stem from a little-understood activation of free-radical damage induced by high intake of alcohol (Meagher et al., 1999) . Because the problems associated with alcoholism have been well documented elsewhere (Abrams, et al., 1987; Schmitz and Gray, 1998) , they need not be discussed here. On the other hand, however, it is becoming clear that moderate wine consumption leased into the blood or converted to acetyl CoA. From this point, metabolism may flow along any of the stan-(ȁ250-300 ml/day, or one-third of a standard wine bottle) has undeniable health benefits. The daily moder-dard biochemical pathways ( Fig. 7 .14). The second metabolic routing is activated only in the presence of high ate consumption of wine can decrease the likelihood of cardiovascular disease, delay the onset of noninsulin-concentrations of ethanol. It involves an inducible enzyme (microsomal ethanol oxidizing system) that oxi-dependent diabetes mellitus, combat hypertension, and reduce the frequency of certain cancers and several other dizes ethanol to acetaldehyde, using molecular oxygen. The activation of this system is undesirable because it diseases. Faced with the diametrically opposed effects of a chemical and beverage that for some is addictive, the generates free oxygen radicals. These are rapidly destroyed by superoxide dismutase and catalase in cells. fluctuations in society's attitude toward alcohol are not surprising (Pittman, 1996; Musto, 1996; Vallee, 1998) . Nevertheless, long-term exposure to the trace amounts of oxygen radicals that survive can result in the slow In this regard, wine drinkers are less likely to demonstrate those alcohol-related problems that have given accumulation of irreparable cellular damage. The subsequent metabolism of the acetaldehyde generated by the alcohol a bad reputation (Smart and Walsh, 1999) . In addition, wine has a higher social image than other bev-microsomal system is identical to that derived by alcohol dehydrogenase. The conversion of ethanol to acetate erages containing alcohol (Klein and Pittman, 1990) . The use of wine as a medicine or as a carrier solution (acetic acid) has the advantage that tissue cells can regulate its uptake. This is not true for ethanol, which can for drugs has a long history, going back at least to the ancient Egyptians . Ancient Greek and diffuse freely through cellular membranes. The control of the ingress of substances into cells is central to the Roman society used wine extensively for medicinal purposes. This practice continued unabated until the begin-maintenance of proper cellular function. ning of the twentieth century. The excessive abuse of distilled alcoholic beverages, combined with religious and Food Value political conservatism, created a backlash against bever-Wine's major nutritional value comes from the rapidly ages containing alcohol, notably in North America. Alcousable caloric value of its ethanol content. Alcohol does hol was viewed as an agent of corruption to be annihinot need to be digested and can be absorbed directly lated. Following the failure of Prohibition, humans through the intestinal wall. In rural viticultural areas, themselves, not alcohol, came to be viewed as the source wine historically functioned as a major sources of metaof evil. Alcoholism is in the late 1900s viewed as a genuine bolic energy for the adult population. Wine in those disease, possessing a complex etiology, with both genetic regions was a food. and environmental aspects. Thus, the social climate is Wine contains small quantities of several vitamins, changing and the legitimate use of wine in medicine is notably the B vitamins, such as B 1 (thiamine), B 2 (riboagain being viewed and investigated seriously. flavin), and B 12 (cobalamin). However, wine is virtually devoid of vitamins A, C, D, and K. In excess, ethanol can impair vitamin uptake. Wine contains divers minerals in readily available forms, especially potassium and iron Alcohol is the primary by-product of fermentative metabolism in many organisms. Ethanol is also an energy (in the ferrous state). Nevertheless, excessive alcohol consumption can disturb the uptake of calcium, magne-source for an even larger number of species. Thus, it is not surprising that enzymes involved in ethanol oxida-sium, selenium, and zinc; and increases the excretion of zinc by the kidneys. The low sodium and high potassium tion are found in most life forms, including humans. In humans, ethanol enters the bloodstream either via content of wine makes it one of the more effective sources of potassium for individuals using diuretics. the consumption of beverages containing alcohol or from ethanol synthesized by the bacterial flora of the intestinal Wine also has several indirect benefits on food digestion. Wine stimulates the production of gastric juices tract. When the concentration of alcohol is low, most of it is metabolized in the liver before it enters the sys- (McArthur et al., 1982) and fosters a healthy appetite. At the levels found in most table wines, ethanol also temic blood flow. Most of the blood supply from the digestive tract passes through the liver before dispersing activates the release of bile into the intestines. Wine acids and aromatics induce the same effects. In contrast, high to the rest of the body. The liver possesses two enzymic pathways for ethanol alcohol levels suppress the flow of digestive juices and the release of bile. At high concentrations, alcohol can metabolism. The primary (constitutive) mechanism involves the oxidation of ethanol to acetaldehyde (via alco-induce stomach spasms. The cultural association of wine with refined eating hol dehydrogenase in the cytoplasm), followed by its oxidation (via acetaldehyde dehydrogenase in the mito-promotes slow food consumption, permitting biofeedback mechanisms to induce satiety and regulate food chondrion) to acetic acid. Acetic acid may then be re-intake. In addition, wine consumption can promote a ing the time wine stays in the stomach, food consumption effectively slows alcohol uptake. Consequently, the liver more relaxed lifestyle, something increasingly valuable in our overly compulsive society. The presence of has more time to metabolize ethanol and, the maximum concentration reached in the blood is more likely to Ͳ-butryolactone in wine may be even more important than wine's alcohol content in reducing stress (Anony-remain acceptably low. The rate of metabolism differs considerably among individuals, with rates commonly mous, 1974). Wine effectively stimulates the appetite in many elderly varying between approximately 90 and 130 mg/kg/h. The hormonal and nutritional state of the individual can and anorectic patients. The mechanism of these influences is unknown. Wine also enhances the release of the hor-also affect the rate of ethanol metabolism. mone gastrin, and, thereby, gastric juices (McArthur et al., 1982) . In addition to aiding food digestion, gastric Antimicrobial Effects juice inactivates enzymes involved in ulceration. Even more significant may be the effect of wine constituents on The prophylactic action of wine against gastrointestinal infections has been known for millennia, long before the bacterium Helicobacterium pylori. H. pylori is considered the primary cause of stomach ulceration. Thus, al-the microbial nature of many diseases was suspected. The antibiotic action of wine is complex in nature and though wine cannot be considered an ulcer medication, moderate wine use appears to have a prophylactic effect not fully understood. The antimicrobial effect of alcohol was discovered in in limiting ulcer development (Brenner et al., 1997) . Wine may further aid human sustenance by increasing the late 1800s. Nevertheless, alcohol is not particulary antimicrobial at the concentrations normally found in nutrient uptake. A series of chemicals, called congeners, combine with metallic ions, vitamins, and fatty acids. wine. Thus, most of the antimicrobial action of wine results from other constituents, notably its phenolic con-This facilitates transport of these components across the intestinal wall. tent. The modification of anthocyanin pigments during fermentation increases their toxicity to viruses, protozo-Finally, consuming wine with food has the added benefit of slowing the rate of alcohol absorption into the ans, and bacteria. Other phenolic compounds commonly found in red wines are also bacteriostatic and fungistatic. blood ( Fig. 12.1 ). Most (ȁ80%) of the alcohol absorbed is taken up through the intestinal wall. Thus, by increas-For example, p-coumaric acid is particularly active Figure 12 .1 Blood alcohol concentrations after wine drinking in a single dose. A, fasting; B, during a meal; C, 2 hours after a meal; D, 4 hours after a meal; and E, 6 hours after a meal (reprinted with permission from Quarterly Journal of Studies on Alcohol, vol. 14, pp. 165-173, 1953 (presently Journal of Studies on Alcohol) . Copyright by Journal of Studies on Alcohol, Inc., Rutgers Center of Alcohol Studies, Piscataway, NJ 08854). and Streptococcus, whereas other phenols inhibit gram-The element vanadium has been shown to have antidinegative bacteria, for example Escherichia, Shigella, Proabetic properties, possibly through its antihypertensive teus, and Vibrio (Masquelier, 1988) . Gram-negative baceffects (Brichard and Henquin, 1995; Teissèdre et al, teria cause serious forms of diarrhea and dysentery. Wine 1996) . Because wine can constitute a significant source is even more effective than some standard antimicrobial of vanadium, it may assist the influence of ethanol in agents, notably bismuth salicylate (Weisse et al., 1995) . delaying, if not preventing, the development of some Thus, it is not without good reason that Roman armies forms of diabetes. In addition, the moderate consumpadded wine to their drinking water when they were out tion of dry wine has no adverse effect on sugar control on compaigns. Red wine is also active against H. pylori in diabetic patients (Bell, 1996; Gin et al., 1992) . Wine (Fugelsang and Muller, 1996) , the causal agent of the also seems to counter some of degenerative effects of diamajority of stomach ulcers. Wine consumption is inbetes. versely correlated with active H. pylori infection (Brenner et al., 1997) . The bacterium is also implicated in gastritis, vitamin B 12 malabsorption, and gastric adeno- High salt (sodium) intake is well known to increase respiratory tract viruses, such as the poliovirus, rhinovithe risk of cardiovascular disease. Therefore, the low ruses, and coronaviruses. Moderate alcohol consumpsodium level in wine does not preclude its use in the tion has also been correlated with a reduced incidence diet of those placed on a low-sodium diet. The high of the common cold in nonsmokers (Cohen et al., 1993) . proportion of potassium to sodium (20 : 1) in wine is The antimicrobial and antiviral effect of phenols and considered to be a positive feature that could recommend tannins is commonly thought to result from their relamoderate wine consumption. tively nonspecific reaction with proteins. Experimental Some of the most significant data relating to cardiovassupport for this view is limited. Because dealcoholized cular disease and alcohol consumption involve broadly white wine, containing neither anthocyanin pigments based epidemiological surveys. These correlate the incinor significant amounts of tannins, still shows significant dence of arteriosclerotic diseases in the United States and antibiotic properties, the search for the antimicrobial Europe with alcohol consumption (Klatsky et al., 1974 ; agents in wine is far from over. Renaud and de Lorgeril, 1992; Fig. 12 .2). These have shown that people who consume moderate levels of alcohol on a daily basis have a significantly reduced incidence Tranquilizer Action of the expression of various stages or forms of cardiovascular disease, for example hypertension (Keil et al. , For the majority of people, alcohol has a suppressive 1998), heart attack (Gaziano et al., 1999) , stroke action on the brain. Thus, alcohol tends to induce drows- (Truelsen et al., 1998; Hillbom, 1999) , and peripheral iness (Stone, 1980) . This explains why small amounts artery disease (Camargo et al., 1997) . Those who conof wine-3 to 6 oz (90-180 ml)-is often beneficial for sume wine moderately live, on average, 2.5 years longer the elderly before going to bed (Kastenbaum, 1982) . than teetotalers, and considerably longer than heavy Elderly patients suffer from insomnia more frequently drinkers. The prime area of contention in these investigathan other groups in the population. This level of intake tions is whether most of the benfits accrue from the gains the benefits of sleep induction, without causing the alcohol or phenolic content (Rimm et al., 1996) . That sleep agitation associated with greater alcohol consumpethanol easily passes into the blood stream is clear. What tion, especially in men (Block et al., 1986) . is less understood is the permeability of the intestinal wall to wine phenolics. The best data relates to the presence of catechin metabolites following wine consumption Arthritis (Donovan et al., 1999) . A number of drugs used in treating arthritis have a Arteriosclerosis apparently results from chronic injury tendency to irritate the lining of the stomach. This side to the arteries ( Fig. 12. 3). Although associated with seveffect is counteracted by the mildly acidic, dilute alcohol eral independent factors, most seem to function primarof table wines. Other beneficial effects connected with ily via the oxidation of lipids in a special subgroup of moderate wine consumption are its mildly diuretic and cholesterol-apoproteins complexes, the low-density limuscle relaxant properties. The diuretic action of wine poproteins (LDLs). Because of the hydrophobic nature can help reduce water retention and minimize joint swellof cholesterol and triglycerides, their transport in the ing. Wine can also directly reduce muscle spasms and blood requires a special transport vehicle. As illustrated in Fig. 12 .4, lipoprotein complexes consist of an outer the stiffness associated with arthritis. membrane of phospholipids, in which apoproteins and also promote the adherence of various blood proteins free cholesterol occur. They enclose a hydrophobic core to the artery wall. In addition, oxidized lipids activate possessing numerous triglycerides and cholesteryl esters. helper T-cells. They, in in turn, induce macrophages (a The specific apoproteins in the complex regulate the scavenger form of white blood cell) to migrate into the metabolism of the associated lipids. Oxidized lipids are artery wall. The macrophages engulf oxidized LDLs, cytotoxic and indirectly irritate the artery wall. They giving the cell the appearance of being full of bubbles. This has given rise to the term foam cells. They initiate localized arterial swelling (plaques). Gradually, oxidized lipids induce the smooth muscle of the artery wall to proliferate. Additional LDLs slowly continue to collect in the artery wall. These accretions may develop their own vasculature, and become fibrous and inelastic. They generate the irregular protrusions into the artery lumen that restrict blood flow and can provoke the various forms of peripheral artery disease. They also set the stage for platelet aggregation, clot formation (thrombus), and the blockage that can precipitate a heart attack or stroke. If the initiators of chronic artery-wall irritation, such as smoking, high blood pressure, high dietary sources of cholesterol, and certain chronic bacterial infections, for example Chlamydia pneumoniae, can be removed, arte- Walzem and Hansen, 1996 , reproduced by permission). sis (from Maxwell, 1997 , reproduced by permission). riosclerosis appears to be at least partially reversible. such as vitamin E and ascorbic acid (Frankel et al., 1993) . There is also direct evidence that resveratrol can enter Part of the reversal relates to elevated levels of highdensity lipoproteins (HDLs). They remove cholesterol the blood system at levels sufficient to have a physiological effect in reducing the action of cyclooxygenases and that has accumulated in the arteries. These lipoproteins are the ''good'' (HDL) blood cholesterols, in contrast to 5-lipooxygenase (Bertelli, 1998) as well as acts as a phytoestrogen. In addition, resveratrol activates proteins in-the ''bad'' (LDL) blood cholesterols, which incorporate fats into the artery wall. The slower the turnover rate volved in nerve cell differentiation, synaptic plasticity (important in learning), and neuronal survival (Tredici of LDLs, the greater the likelihood of oxidation . Moderate wine consumption, notably of et al., 1999) . Additional potent antioxidants in wine are flavonols, such as quercetin, and tannin subunits, such red wines, increases the concentration of HDLs, decreases the level of LDLs, and increases the rate of their as catechin (Miller and Rice-Evans, 1995) . They not only are more effective antioxidants than resveratrol, but also degradation (turnover) in the blood. A favorable HDL/LDL protein ratio is produced by occur at higher concentrations. Their content depends partially on the duration of maceration and fining used the moderate consumption of alcohol. This may result from the additional synthesis of insulin in the presence in wine production. For example, fining with PVPP (polyvinylpolypyrrolidone) markedly reduces the quer-of both glucose and ethanol. The enhanced insulin production is of special significance to those with a genetic cetin content (Fluss et al., 1990) . or environmental predisposition to Metabolic Syndrome X, a disorder of carbohydrate metabolism that develops as tissue cells become resistant to the influence of insulin. The result is a progressively chronic, high circulatory- The aggregation of platelets, the formation of a clot, glucose level (hyperglucemia). This, in turn, results in the blocking of blood vessels, and the associated oxygen chronically high concentrations of triglycerides and LDL deficiency that results are central steps in the damage cholesterol in the blood. Estrogens have an effect similar caused during a heart attack or stroke. Thus, it is not to moderate ethanol consumption, that is, reducing trisurprising that inhibitors of platelet aggregation reduce glyceride and LDL contents in the circulatory system the frequency of these cardiovascular events. It is the (see Bisson et al., 1995) . rationale for recommending the daily consumption of In addition to the effects of ethanol, various phenolic ASA (acetylsalicylic acid, an inhibitor of platelet aggregawine constituents have protective effects against cardiotion). Ethanol has a platelet inhibitory action (Renaud vascular disease. Phenolic compounds are particularly and Ruf, 1996) , as well as phenolics found in red wine active as antioxidants and inhibitors of platelet aggrega-( Fig. 12 .5). Many flavonoids, such as catechin, epication. Regrettably, the large number of phenolic comtechin, and quercetin, markedly inhibit platelet aggregapounds and the complexity of their metabolism has retion (Keli et al., 1994) . This may be a consequence of sulted in little direct (in vivo) evidence of these influences the production and release of nitric oxide by endothelial (Carbonneau et al., 1998; Folts, 1998) . One of the more significant consequences of wine phenolic compounds is limited LDL oxidation (Maxwell et al., 1994; Rice-Evans et al., 1996) . This probably results from the inhibition of lipooxygenases, as well as the scavenging of free oxygen radicals and chelate iron (involved in radical formation) (Morel et al., 1994) . In addition, tannin subunits (catechins and epicatechins) appear to protect other cellular components from oxidation. Other antioxidants of importance in the human diet are vitamins E and C (tocopherol and ascorbic acid), ͱ-carotene, and selenium. The occurrence of tocopherol in the precursor of LDLs may provide a natural, but short-term, protection from oxidation. One of the unique antioxidants found in wine is resver- has greater antioxidant action than dietary antioxidants cells of blood vessels. This can be activated by the expo-is new is the observation that wine consumption further reduces the likelihood of production of these painful and sure of endothelial cells to grape extracts (Fitzpatrick et dangerous inclusions (Curhan et al., 1998 (Curhan et al., ). al., 1997 . Nitric oxide induces vasodilation (by relaxing vascular smooth muscle), decreases platelet aggregation, and limits platelet adhesion to blood vessel endothelia. Indicative of the complexities of these effects is the obser-As in many other areas, the consumption of a modervation that flavonoids also inactivate nitric oxide (Verhaate amount of wine can reduce the risks of certain cangen et al., 1997) . Nitric oxide, notably as peroxynitrile, cers, whereas increased consumption provokes some oxidizes LDLs. Resveratrol also been noted to decrease cancers (see Ebeler and Weber, 1996) . At the concentrathe adhesion of blood constituents that promote platelet tions typically found in wine, ethanol has an inhibitory aggregation to vessel walls (Bertelli, 1998) . effect on the carcinogenesis of ethyl carbamate. Certain wine phenolic compounds also can be protective, whereas others, or a higher concentration, can be muta- genic. For example, quercetin can induce mutations in One of the latest in the growing list of correlations laboratory tissue culture, but is a potent anticarcinogen between moderate wine consumption and improved in whole-animal studies (Fazel et al., 1990) . This apparhealth is a decrease in the prevalence of age-related macuent anomaly may result from differences in the concenlar degeneration (Obisesan et al., 1998) . This is the leadtrations of quercetin used, and the low level of metal ions ing cause of blindness in adults over 65. It is a degeneraand free oxygen found in the body (vs. tissue culture). In tive disease that results in blurred or distorted vision. addition, phenolics can detoxify the small quantities of The disease may progress slowly or suddenly, as vessels nitrites commonly found in food. However, in the presbelow the retina bleed or exude fluid. ence of high concentrations of nitrite (a preservative found in smoked and pickled foods) nitrites are converted into diazophenols (Weisburger, 1991) , which can Gout induce oral and stomach cancers. Resveratrol can inhibit In the 1800s, there were many reports linking wine the production of cyclooxygenase-2, thought to be imconsumption, especially port, with gout. This association portant in carcinogenesis (Subbaramaiah et al., 1998) . It also is a major inhibitor of human P450 1A1 (Chun is no longer tenable. Gout is caused by localized crystalliet al., 1999) , an important aryl hydrocarbon hydroxylase zation of uric acid in the joints and the associated inthat can convert environmental toxicants and procarcinflammation. This frequently results as a consequence of ogens into active carcinogens. In addition, flavones and reduced excretion of uric acid by the kidneys. Wine can flavonols strongly restrict the action of the common dioccasionally aggravate the situation as a consequence of etary carcinogens, heterocyclic amines (Kanazawa et al., alcohol metabolism; the lactic acid produced as a result 1998) . It is estimated that these compounds, produced reduces uric acid elimination by the kidneys. Alcohol during cooking, are consumed at a rate of approximately can also raise blood uric acid level, by promoting purine 0.4 to 16 Ȑg per day (Wakabayashi et al., 1992) . The breakdown (the prime source of uric acid). In this regard, antiallergic and antiinflammatory properties of flavowine is less likely to induce gout than beer, due to wine's noid phenolics probably also contributes to the anticanlower purine content. Nevertheless, medical historians cer aspects of these chemicals (see Middleton, 1999) . suspect that lead-induced kidney damage was the pri-Moderate wine consumption is not linked to an inmary cause of the gout epidemic during the nineteenth creased risk of cancer, with the possible exception of a century (Emsley, 1986 (Emsley, -1987 Yu, 1983) . Samples of slight increase in the incidence of breast cancer (Viel et port from the 1800s show high lead contents. Lead pickal., 1997) . Findings from the long-duration Framingham up from stills (used in making fortifying brandy) proba-Study, however, indicate no relation between moderate bly was the primary source of the contamination. In alcohol consumption and the incidence of breast cancer addition, pewter and lead-glazed drinking cups and the (Zhang et al., 1999) . In contrast, high rates of wine prolonged storage of wine in lead crystal decanters could consumption have been linked with an increased incihave further augmented the lead content of port. dence of mouth and throat cancers (Barra et al., 1990) . Ethanol itself is not carcinogenic, but can enhance the transforming effect of some carcinogens. High water consumption has long been known as a Allergies and Hypersensitivity significant factor in reducing the incidence of kidney stones. The associated increased urine production helps Sulfur dioxide is potentially the most significant irritant in wine. For a small proportion of asthmatics, sulfur to prevent the crystallization of calcium oxalate. What dioxide may induce bronchial constriction (Dahl et al., non has come under closer scrutiny. Central to continued progress in this research is the realization that wine may 1986). Usually, sulfite is rapidly converted to sulfate by sulfite oxidase. However, low levels of this enzyme could be associated with several differentiable headache syndromes. permit sulfite to persist, provoking problems in those hypersensitive to the compound. It could explain the One of the most severe headaches that may be associated with wine consumption is migraine. Migraines may rapid onset of an asthma attack because the absorbed sulfite is transported via the blood to the bronchi. At be induced by a wide range of environmental stimuli, possibly because migraines are themselves a complex of potentially a greater risk are individuals afflicted with a rare genetic disease, sulfituria (Shih et al., 1977; etiologically distinct events. The dilation of blood vessels in the brain, as a result of histamine release, can be the Crawhall, 1985) . They are unable to produce active sulfite oxidase. Consequently, they must live on a very re-common element in many instances of headache development. When red wines were discovered to have higher stricted diet, low in sulfur-containing proteins. It is estimated that the synthesis of sulfite, associated with concentrations of biogenic amines, such as histamine and tyramine, there was the initial assumption that they normal food metabolism, generates approximately 2.4 g sulfite/day. The sulfites in wine contribute only margin-were the culprit. However, it was later realized that the histamine levels normally found in red wines are below ally to this amount. Because of the gravity of sulfituria, most affected people die before reaching legal drinking those that normally could trigger a migraine. In addition, double-blind studies have seemingly exonerated hista-age. Idiosyncratic allergic and other immune hypersensitive mine in red-wine-induced migraine headaches (Masyczak and Ough, 1983) . Nevertheless, alcohol can suppress responses are difficult to predict or diagnose. Reactions may include the induction of headaches, nausea, vomit-the action of diamine oxidase, an important enzyme of the small intestine that inactivates histamine and other ing, general malaise, or a combination of these. The small quantity of fining agents left in wine has been biogenic amines ( Jarisch and . Thus, in individuals with histamine intolerance, sufficient hista-implicated in some allergic reactions (Marinkowich, 1982) . Various tannic compounds have also been sug-mine may enter the blood system to provoke a vascular headache. gested as the causal agents of certain problems, especially in those showing reactions to red, but not white, wine. In the treatment of the possibly closely related clusterheadache syndrome, small doses of lithium may be pre-With over 600 compounds potentially occurring in wine, it is not surprising that there are individual adverse reac-ventative. Because some red wines have a higher than average lithium content, they may prevent, rather than tions to specific wines or wine types. An intriguing allergy-like reaction is the rapid face induce, headaches. Although the biogenic amine content of wine appears and neck flushing commonly experienced by Asians after the consumption of a small amount of ethanol. This to be insufficient to cause migraines in most individuals, tannins and other phenolic compounds in wine can pro-phenomenon, presumably genetically controlled, is prevented if antihistamines are taken in advance of the alco-voke headache development. Because red wines contain significantly more phenolic compounds than white wines hol challenge (Miller et al., 1988) . Antihistamines have also been shown to counteract bronchoconstriction fol-(ȁ1200 mg/liter vs. 200 mg/liter), red wines are more frequently associated with headache production. Pheno-lowing red wine consumption in nonasmatics . This situation appears to result from intol-lic compounds that enter the blood stream suppress the action of platelet phenolsulfotransferase (PST) ( Jones et erance to the low levels of histamine found in wine. In addition to physiological reactions to wine constit-al., 1995). Thus, individuals initially having low levels of platelet-bound PST are more susceptible to migraine uents, there are a wide range of equally important psychological responses (Rozin and Tuorila, 1993) , both headaches (Alam et al., 1997) . The suppression of PST activity results in reduced sulfation (inactivation) of bio-positive and negative. Traumatic memories associated with the first exposure to, or excessive consumption of, genic amines and catacholamines. Thus, these compounds are more likely to stimulate the release of 5-a particular beverage can create an association that lasts a lifetime. Other people have come to associate certain hydroxytryptamine (5-HT, or serotonin), which acts as an important neurotransmitter in the brain. 5-HT also products with social groups, lifestyles, or behavior. Such attitudes can make the beverage socially unacceptable. promotes platelet aggregation and the dilation of small blood vessels in the brain. This can cause pain and instigate the development of a migraine (Pattichis et al., 1995) . People prone to migraine headaches occasionally show abnormal and cyclical patterns in platelet sensitiv-People may avoid the consumption of certain wines because their association with headaches. This phenome-ity to 5-HT release ( Jones et al., 1982; Peatfield et al., 1995) . This may explain why wine consumption is not are even less well understood than those evoked by red wines. In some individuals, headaches may be associated consistently linked to headache induction. Small phenolic components in wine also prolong the action of potent with a sensitivity to sulfites, which are commonly found in higher concentrations in white wines than red wines. hormones and nerve transmitters, such as histamine, serotonin, dopamine, adrenalin and noradrenaline. These There is one more, well-known, headache phenomenon-the hangover. In this case the etiology is well can affect headache severity and other allergic reactions. Large tannin polymers, unlike their subunits, do not known. Despite its all-too-frequent occurrence, the precise mechanism remains unclear. Various compounds enter the blood. This may explain why aged red wines tend to be less associated with headaches than their have been implicated, notably ethanol (and its primary breakdown products, acetaldehyde and acetic acid) and younger counterparts. A classic example is the ease with which the youngest of all red wines, Beaujolais nouveau, methanol (and its metabolic by-products, formaldehyde and formic acid). None of these have been confirmed, produces headaches in those prone to their occurence. Another recognized headache syndrome is the ''red individually or collectively, as being specifically causal. There is no known effective treatment. Prevention, or wine headache'' (Kaufman, 1986) . It may develop within minutes of consuming red wine and is often dose-related. time, are the only cures. Taking wine with meals is a long-known precaution. The headache reaches its first peak within approximately 2 hours, tends to fade, but returns roughly 8 hours later Food delays the movement of alcohol into the intestinal tract, where some 80% of the alcohol is absorbed. Be-in a more intense form. The headache seems related to the release of prostaglandins, important chemicals cause the uptake is slowed, the absorption more evenly matches the body's ability to metabolize alcohol. It also involved in dilating blood vessels. Thus, the development of such headaches is often prevented by the prior con-delays the uptake of phenolic compounds and diminishes the maximum concentration that accumulates in the sumption of prostaglandin synthesis inhibitors, such as acetylsalicylic acid (i.e., aspirin), acetaminophen (i.e., blood. Tylenol), and ibuprofen (i.e., Advil) (Kaufman, 1992) . An interesting discovery is the influence of resveratrol in inhibiting the expression of cyclooxygenases in tissue cells ( Jang and Pezzuto, 1998) . These enzymes catalyze Fetal alcohol syndrome (FAS) refers to a set of phenomena including suppressed growth, mild mental retar-the synthesis of prostaglandins. This could mean that some wine phenolic compounds may have a suppressive dation, and facial abnormalities. It is most often found in the children of alcoholic mothers. Initially, there was rather than an inducing influence on headache production. Ethanol may also be involved via direct or indirect concern that moderate wine consumption during pregnancy might cause FAS. However, the real cause of the increases in the levels of prostaglandins (Parantainen, 1983) . If so, ethanol may actively participate in headache detrimental effects observed in FAS is unknown. The problem is complicated because alcoholic mothers also production in sensitive individuals. The ability of some yeasts to produce prostaglandins tend to be heavy smokers, use illicit drugs, consume large amounts of coffee, have poor nutrition, or show a (Botha et al., 1992) introduces the intriguing possibility that they may occur as constituents in wine. If so, yeast-combination of these (see Scholten, 1981; Whitten, 1996) . Although there is no absolutely safe level of alco-derived prostaglandins could be an additional source of headaches in sensitive individuals. They might also be hol consumption, or of consumption for any food for that matter, there now seems no reason to suspect that involved in inflammatory lung diseases such as asthma. An additional wine-related headache has been given taking a glass of wine with meals should harm the developing fetus. A small amount of alcohol is periodically the name ''red head' ' (Goldberg, 1981) . It develops within an hour of waking, after drinking no more than found in the blood due to the action of the natural bacterial flora in the intestines. Thus, alcohol is a natural two glasses of red wine the previous evening, and consists of headache and nausea. The headache becomes very component in the human diet, even if we never drink a beverage that contains alcohol. severe while reclining. Although the headache is relieved somewhat by standing, this itself exacerbates the nausea. The headache usually lasts a few hours before dissipat-Contraindications ing. A similar phenomenon has been reported with some Californian Chablis, or mixtures of white wine, taken The most important contraindication relates to those with a past history of alcohol abuse or alcoholism. For alone or with coffee or chocolates. Its chemical cause is unknown (Kaufman, 1986) . the majority of the adult population, however, moderate wine consumption appears to have considerable health Some headaches are associated only with the consumption of white wines. Its characteristics and etiology benefits. Nevertheless, there are several situations in which wine consumption, even in moderate amounts, chloramphenicol, sulfonylurea, metronidazole) when consuming alcoholic beverages can also produce a simi-can complicate or diminish the effectiveness of disease treatment. lar response in sensitive individuals. the mouth, throat, stomach, and intestinal tract. Other In addition to the antabuse reaction just noted, conconstituents in wine may also be detrimental in this resumption of alcohol can generate various unpleasant to gard. Thus, all beverages containing alcohol are usually dangerous reactions in some individuals. Regrettably, contraindicated in cases of gastritis, gastric cancer, and most of the literature relating to alcohol-drug interacbleeding in the upper digestive tract. Nevertheless, the tions come from studies of alcoholics or binge drinkers. action of red wine against H. pylori and the suppression This potentially limits its significance to most situations. of histamine production by the gastric mucosa (Masque-Nevertheless, even small amounts of alcohol can cause lier, 1986) may require a reconsideration of the old prothe loss of muscle control in some individuals taking hibition. In the presence of pancreatitis, alcohol is absotricyclic antidepressants. In addition, red wines can relutely contraindicated. duce the effectiveness of MAO (monoamine oxidase) 2. In liver disease, the consumption of wine is normally inhibitors, used in controlling hypertension. The longcontraindicated. The presence of alcohol puts additional term use of acetaminophen can enhance alcohol-induced stress on an already weakened vital organ. Chronic alcokidney damage. hol abuse can lead to cirrhosis of the liver. Other contraindications involve the intensification of 3. In acute kidney infection, wine should be avoided. the effects of barbiturates and narcotics. In combination The consumption of alcohol increases the burden on an with certain antidiabetic agents, such as tolbutamide and organ essential to eliminating toxic metabolic wastes. chlorpropamide, alcohol can cause dizziness, hot flushes, 4. In prostatitis or genitourinary infections, the conand nausea. Mild reactions may occur with a wide range sumption of alcohol can complicate matters. The diuretic of other medications, such as sulfanilamide, isoniazid, action of wine may increase the frequency of urination and aminopyrine. Details may be found in Adams (1995) or, conversely, it may induce highly painful urinary reand Becker (1982). tention. 5. In epilepsy, the consumption of even moderate amounts of wine may increase the frequency of seizures in some patients. 6. In patients about to undergo surgery, the generally beneficial effect of alcohol on reducing the aggregation The association of wine and food is frequently disof platelets is undesirable. Thus, it is recommended that cussed in print, but is a topic about which little substanpatients terminate any alcohol (as well as aspirin) contive is known. Most comments are simply expressions sumption before surgery. This avoids increasing the inciof personal opinion. This is acceptable if the reader is dence of intra-and postoperative bleeding (Wolfort et interested in the viewpoint of the author. However, it is al., 1996). not the basis for an understanding of the principles of food and wine combination nor of the influences of cul-The consumption of alcohol is also ill-advised when ture and the environment on them. eating certain mushrooms. The most well-known exam-One of the few serious studies on food combination ple is the antabuse reaction associated with joint conwas conducted by . It attempted to compare sumption of Coprinus atramentarius. Another mushdifferent food ingredients on the basis of flavor intensity. room reportedly generating the same response is Boletus From this, recipes and whole meals could be designed luridus (Budmiger and Kocher, 1982) . The antabuse reon the basis of how flavor intensity was to develop action derives its name from the trade name of disulthroughout the meal. Although difficult to use in practice firam, a medication used in the treatment of alcoholism. due to the various influences of food preparation on When even small amounts of alcohol are consumed when flavor, his work did highlight the importance to flavor taking disulfiram, a very unnerving reaction follows. intensity, balance, and development in Western cuisine. This may include symptoms such as flushing, sweating, Although different in intent, the works of Prescott and weakness, vertigo, blurred vision, difficulty breathing, Stevenson (1995) and Taylor (1996) have clarified spenausea, chest pain, palpitation, and tachycardia. In secific aspects of flavor perception and preference. vere cases, the disulfiram-alcohol reaction can provoke In most situations, the entree is the central element of acute congestive heart failure, convulsions, and death. Using certain drugs (e.g., cephalosporins, griseofulvin, a meal, for which everything else is only a foil. Only rarely is wine the central component with the solid meal constituents chosen to reflect the qualities of the wine. As noted, harmony in flavor intensity is a major princi- ple in Western cuisine. Although the formulation of the principle is intellectually gratifying, most people are in-There is an extensive series of wine-food interactions. sufficiently familiar with the flavor intensities of wines The most well-known involves wine tannins and food to find the principle of much practical use. Charts such proteins. The reaction reduces the bitterness and astrinas that in Fig. 12.6 and Beckett (1998) help, but yearly gency of young tannic wines. In addition, the flavor of and stylistic variation limit their value. Furthermore, red meats helps to mask the bitterness of many young red food preparation (boiled, baked, fried, or barbecued), wines. Food proteins also reduce the sour and astringent sauce employed (white, cream, brown, or curry), or servcharacter of some dry white wines. This partially exing temperature (cool, warm, or hot) can markedly affect plains the typical combination of red wine with meat the flavor intensity of food. The situation becomes even and dry white wine with fish. Of greater significance, more complex with a series of dishes. In this situation, however, may be the balance in flavor intensities. Thus, the problem is normally avoided by providing different neither wine nor food flavors dominate. Alternatively, wines with each course. the peppery flavor of some tannins or the sharp bite of Put in historical perspective, wine selection is a relamarked acidity may enhance food flavor-similar to the tively new phenomenon. European cuisine did not start role of spices. Another interpretation of traditional to emerge from the morass of medieval cookery until the food-wine associations is habituation. Europeans simsixteenth century. Grand medieval meals often involved ply may have come to appreciate the typically acidic, several simultaneous combinations of soup, meat, fish, tannic sensation of wines with their food. poultry, and sweet dishes. With such a chaotic medley, Although taste and touch interactions are more apparmatching wines would have been inutile. In addition, ent, odor interactions also occur. Most famous food and poor transportation limited the range of wines available wine combinations primarily relate to their aesthetically even to the richest nobility. Furthermore, without sulfur pleasing, aromatic interactions. Because of the imprecise dioxide, the finest wines were usually those less than a state of our understanding of odor perception, especially year old (wine in barrels often turned vinegary by the in complex mixtures, a clear explanation of such celesummer following the harvest). Thus, wines would not brated associations is impossible. have matured sufficiently to develop the flavors we now When appropriate combinations result in an increase consider synonymous with matching wines with food. in joint appreciation, one has what is normally referred Improving economic conditions-associated with exto as harmony and balance. Interestingly, desirable assoploration, a burgeoning middle class, and industrializaciations often occur when opposed tastes or flavors comtion-provided conditions in which the demand for, probine in a dynamic, seemingly unstable, equilibrium. Exduction of, and transport of wine grew proportionately. amples of some of the more well-known opposed These changes favored refinements in eating. This culmicombinations are the associations of port with Stilton nated in the division of meals into a sequence of soup, cheese, Sauternes with Roquefort cheese, venison with fish, salad, meat, cheese, and dessert courses by the nineauslese, Sancerre with goat cheese, and crab with chablis. teenth century. Thus, improved wine availability, and The rationale for the combination of sweet, richly flathe rediscovery of the benefits of wine aging, occurred vored wines (ports and sauternes) with salty, creamy along with a rebirth of culinary sophistication. Both blue cheeses (Stilton and Roquefort) seemingly relates features probably encouraged the pairing of wines with to their similar richness and the blend of salt and sweetthe meal. ness. The complexities of their flavors integrate, enhanc-However, long before people became concerned with ing mutual enjoyment. In Germany, the gamey character matching wine with food, local wines developed intimate of well-aged venison is considered to be counterbalanced associations with regional cuisines. This included not by the sweet, rich flavors of a fully mature 'Riesling' only wine's role as the preeminent food beverage, but Auslese. In the Loire, the aggressive dry acidity of Sancalso its role in food preparation. erre is viewed as counterpoised when taken with the In food preparation, cooks use wine in several ways. racy goat cheeses of the region. Finally, the sourness of Possibly one of the most ancient is as a marinade. The Chablis is deemed to be offset by the sweet flavor of acids in wine tenderize meat, as well as temporarily precrab. Although some combinations of opposed tastes are serving it. Wine vinegar has been used even more extenhighly regarded, it is more common in Western cuisine sively in pickling foods. Wine also has been employed to stress subtle balances between compatible tastes and odors. to extract or mask the gamey flavor of wild meats. Be-cause the marinade is usually discarded, the wine seldom the dilution of the alcoholic content by the food helps liberate some wine aromatics (Fischer et al., 1996 ; significantly modifies the food's flavor. Another long-established culinary application of wine Fig. 11 . 12). is in poaching, stewing, or braising. Because cooking dramatically changes the wine's flavor, there is little value in using fine wines. The prime concern is that the In a study of the principles that underlie world cuiwine should not adversely affect the food's flavor. Wine sines, Rozin (1982) grouped culinary styles according to color is seldom important because prolonged heating their use of primary ingredients, cooking techniques, and turns the wine brown. unique flavorants. Of these, the most distinctive was the Carbon dioxide in the wine escapes during cooking, use of flavorants. For example, east Asian, East Indian, even more rapidly than does its alcohol content. Thus, Mexican, and Italian cooking were characterized by their other than for show, the use of a sparkling wine instead use of soy sauce, curry, tomato and chili peppers, and of still wine is valueless, unless it is added just before a sauce combining olive oil, tomato, garlic, and herbs, serving. Cooking promotes the evaporation of ethanol, respectively. Condiments often give regional cuisines but its loss is often much slower than generally realized their distinctive character. (Table 12 .1). The intensity of some regional seasoning may seem to When poaching or braising in wine, the fluid is often give the food a monotonous similarity. However, the reduced to make a sauce. Alternatively, wine may be incredible variation in chili peppers, curry preparations, added to deglaze the pan. Because deglazing exposes the and soy sauces can provide a rich diversity of sensory wine to less heating, the sauce will possess more of the nuances to those habituated to the basic sensations. This natural flavors and color of the wine. The more the cook is probably equivalent to the apparent similarity of wines wants the original wine flavors to appear in the food, to those unaccustomed to their consumption. the later the wine should be added. This also requires Especially interesting is the appreciation of the burning more care in selecting the wine. sensation of chilies, the bitterness of coffee, or the sour-Only sweet wines are compatible with dessert, notably ness of pickled foods. The rapid and widespread accepof fresh, fully mature, low-acid fruits, such as strawbertance of intense flavors, initially perceived as painful or ries, peaches, or apricots. Nevertheless, dry wines may harsh, is in stark contrast to the slow spread of neutralbe used as a fruit marinade, act as a poaching fluid for flavored foods such as corn or casava. Intriguingly, Eufirm fruit, be incorporated into a sherbet, or function as rope and other northern climatic regions have, in the a blending medium for creamy custards. past, largely resisted the spread of chili pepper use into In its more traditional role as a food beverage, wine their cuisine (Andrews, 1985) . plays several functions. At its simplest, wine acts as a Pairing wines with food is little more than 300 years palate cleanser. By rinsing food particles and substituting old. Much of this evolved under the influence of Frenchits own flavor, wine minimizes sensory fatigue. Thus, modified Italian cuisine, itself adopted from the Middle the food maintains its flavor and appeal unabated East during the Italian Renaissance. Thus, the acceptance throughout the meal. In its turn, food helps freshen the and appreciation of acidic, often tannic, wine may be palate for the wine. accidental. Many North Americans, growing up with Wine also has an important solubilizing action. The sweet-tasting beverages, consider dry table wines vineacidic and alcoholic components of wine improve the gary-at least on first exposure. As with chilies and black solubility or volatilization of certain food constituents. coffee, only a small proportion of the population who In so doing, wine aids food perception. Conversely, are unaccustomed to these tastes early in life freely adopt them in adulthood. Even here, societal pressure may be central in shaping adult preferences to accepted norms. Simmered (2 h) 10 Of the four primary taste sensations, wine possesses only three-sweet, sour, and bitter. Because most basic a Data from Augustin et al. (1992) . food ingredients exhibit neither sour nor bitter tastes, the old dictum of ''selling wine over cheese, but buying it over water.'' there is little obvious logic in their association with food. However, food does depress the sour, bitter, and astringent aspects found in many table wines. Proteins in food Complex or Grand Meals have already been mentioned as minimizing the sensory Although preparing grand or complex meals is not impact of tannins and acids in wine. This results in the normally an everyday activity, a brief discussion of such wine tasting smoother, less sour, and better balanced. events, and their rationale, can be useful in determining Thus, in many cases, it is the food that enhances the how one might present simpler meals in a grand fashion. perception of the wine, rather than the reverse. Neverthe-It is normally considered wise to maintain a beverage less, the acidity of wine tends to freshen the mouth, consistency throughout the meal. One should either preswhereas moderate bitterness and astringency can enliven ent beverages based on grape or grain products. Mixing bland foods. the two during a meal typically has not been found com-Wines and foods seldom have similar flavor qualities. patible. For example, the predominant flavor qualities of wines, Typically, a grand meal will commence with an aperisuch as fruitness, floral notes, vegetal, and oaky aromas, tif. Classic versions are dry (fino) sherries or sparkling are rarely found in the basic ingredients of a meal. Conwines. To many palates, however, a 'Riesling' Kabinett versely, common food flavors are seldom found in wines. is a more pleasing introit, with its finely tuned balance Occasionally, however, a flavor component of a wine between acidity and fruit flavor. may complement a similar essence in the food. Examples After hors d'oeuvres and an aperitif, a light, clear soup are the nutty aspect of cream sherries and a walnut or plain salad is served. Typically, this comes without a dessert, or the oaky character of wines and the smoke beverage, especially if the salad contains a vinegar-based flavors of meat roasted over hardwood charcoal. dressing. Subsequently, a light course consisting of fish Although the taste of most foods is not inimical to or fowl is presented. Generally, this is accompanied with wine, several flavorants are, at least to the sensibilities of a dry white wine. Examples might be a Saumur, Riesling, most Europeans. Vinegar and vinegar-based condiments or Pinot Bianco with poached sole fillet; a traditional enhance the sour taste of table wine, making them harsh white Rioja, Greco di Tufo, or oak-aged Chardonnay even to those who relish dry wines. The burning sensawith sole almandine; or a Fume Blanc, Hermitage Blanc, tion of chilies and most curries deaden the taste buds to or Gewü rztraminer with fried trout. The next course the subtleties of wine. In addition, heavy doses of spices could be a light citrus sherbet, or terrine, principally to mask the aesthetic attributes of fine wine. cleanse the palate and prepare for the entree. Because Western cuisine typically aims to balance food and the entree is customarily a meat dish, one or a number wine flavors. The adage of red wine with red meats and of red wines would be served. Typically, the youngest white wine with fish crystallizes this concept. The rule wine is served first and the oldest last. This retains the focuses attention on balancing savory, dark-colored oldest and most subtle wine for the last; otherwise, the meats with flavorful red wines, and the milder-tasting, younger wines would appear increasingly rough and unpale-colored meats and fish with the delicacy of most distinguished. Often, the best red is presented after the white wines. Regrettably, the expression glosses over the entree, possibly with a mild smooth cheese. effects of cooking techniques and condiments on food With, or instead of, dessert, a superior-quality sweet flavor. The adage also neglects the influence of other table wine may be served, such as a select-late-harvest important aspects of flavor perception, namely its com-'Riesling'; an auslese, beerenauslese, or trockenbeereplexity, development, and duration. Occasionally, hownauslese; or a Sauternes. Alternatively, one might be ever, a mild wine may be chosen to moderate strong served a sweet fortified wine, such as a palo cortado, a food flavors. Conversely, a delicate food may be chosen setubal, or a sweet sparkling wine. Later in the evening to highlight the complex subtlety of a well-aged red wine. one might have a tawny or vintage port. It is much easier to indicate situations in which wine Usually, the better the wine, the plainer the food prepaand food will clash, than suggest sublime combinations. ration should be. This allows the subtleties of the wine Cheeses are often associated with wine tastings. Nevto develop and be experienced in all their glory-not ertheless, strong-flavored cheeses often mask the subtlety masked by intense food flavors. of fine wines, and mild cheeses may contribute little to wine appreciation. Salty cheeses can, however, miracu- lously reduce the bitterness and astringency of many tannic red wines. In addition, fine-flavored cheeses can Rarely is choosing the ''right'' wine (if such an entity exists) of critical importance. Nonetheless, half the joy enhance the apparent quality of mediocre wines. Thus, in preparing a meal may come from selecting the wines the ambiance of the occasion. 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