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Home , Dietary fiber, Food pyramid (nutrition), Glycemic load, Mediterranean diet

In 21 ND 21 16,18 The Paleolithic , The Paleolithic 17 by John Neustadt, The , found primarily in 17 Additionally, Additionally, in the year 2000, grains, 17 NFLAMMATION 19,20 ), while in the Western diet is ), in while the sodium form in the Western Additionally, Additionally, this diet contained a potassium-to- Integrative Medicine • Vol. 5, Medicine • Integrative No.Aug/Sept 2006 • 4 and has a potassium-to-sodium ratio of 3 I 15,16 Summarizing the major differences between ances- In contrast, the post-Agricultural Revolution diet, which contained with the Paleolithic In contrast 15,22 addition, the typical Western diet has been estimated to contain 16 to 30 times more omega-6 than omega-3 fat , is mostly in the form of (KHCO potassium bicarbonate foods. This diet, commonly called the or diet, Hunter-Gatherer had predominated for about 2 mil- lion years. According to AP researcher into Simopoulos, the effects of a polyunsaturated fatty acids leading on and disease, the Paleolithic diet contained 19% to 36% and 22% intakes of 520 mg to , to 100 150 g 690 , mg 46% ; daily C; mg 400 and , mg 2000 to 1500 sodium, and a polyunsaturated-to-saturated 1.41. ratio of of sodium chloride Therefore, (NaCl) the imbalance of potassium from to sodium in the processed chlo- dietary elevated by accompanied also is diet foods. Western con- dietary bicarbonate decreased and consumption ride sumption. 1:1.25–3.75. tral tral diets and the Western by (1) an characterized are industrialized societies “Today diet, Simopoulos writes, increase in energy intake and decrease in energy expendi- Western Western diet, also called the (SAD), Standard is American radically diet different high a by characterized is dietary pattern from Western Today’s our ancestors’ diet. intake of saturated fatty acids, processed trans foods; fatty and low acids, intakes and of fatty and acids, unsaturated micronutrients. , mono- and poly- The foods most commonly consumed deli (eg, processed , grain-fed are dietarypattern in the Western or hotdogs), refined-grain products, , French fries, high-fat dairy products, and desserts. sweets and other no refined , in 2000 the consumption of all refined kg in 1970. 55.5 kg, up from in the US was 69.1 of course, was devoid of all processed foods. sodium ratio of approximately 10:1. sodium of ratio approximately such as and , were consumed at a rate pounds per of person per year in the . 200 1 5 5 3,4 In 8-13 7 IET AND Research Research suggests 2 D 1 and in the coming decades 6 This article reviews the role diet 14 and these risk factors may account for up to 80% to up for account may factors risk these and ESTERN 2 ESTERN DIETARY PATTERN W Since the Agricultural Revolution approximately A common factor that may contribute to the develop- may A common factor that is responsible for 25% of US deaths and is the is and deaths US of 25% for responsible is Cancer The prevalence of chronic, degenerative diseases HE of large bowel, breast, and prostate . that that about one-third of all cancer deaths are attributable to poor , physical inactivity, and overweight or ; may may erode the national gains in life expectancy. fact, several pathologies that were once viewed as unrelat- ed are now grouped by some researchers and ofcategory the into clinicians ath- including disease,” “inflammatory erosclerosis, , arthritis, vasculitis, , and autoimmune diseases. T Overweight (defined as body mass index [BMI] of 25- 29.9) and obesity (BMI ≥30) are at epidemic levels, with 65% of US adults classified Nearly as one-third of overweight US or children obese. are being either overweight at or risk are for already overweight or Obesity obese. contributes to more than 280,000 deaths each year in the United States, CVD, CVD, the number-one cause of mortality in the States, United accounted for of 37.3% all US deaths in 2003, and was “an underlying or contributing cause” for approxi- mately 58% of deaths in 2002. W 10,000 years 10,000 ago, dietary and lifestyle patterns have dra- matically changed. Prior to the revolution, people con- sumed an enormous variety of wild and ment and progression of these illnesses is chronic inflam- mation, which can be caused and modified by diet. second leading cause of mortality. attributable attributable wholly or in part to dietary patterns is most serious the threat to public health in the United States. (CVD), can- disease cardiovascular These diseases include The mellitus, and overweight/obesity. cer, numbers are truly staggering. One adults third (more than of 71 million American people) have one or more types of CVD, including 13.2 million cases of coronary heart disease (CHD) and 65 million cases of high blood pressure (HBP, defined as systolic blood pressure ≥140 mm Hg and/or diastolic blood pressure ≥90 mm Hg). plays plays in creating in the body.

COMMENTARY 14 ture; (2) an increase in , omega-6 fatty acids response to noxious stimuli (eg, environmental factors, and trans fatty acids, and a decrease in omega-3 fatty acid , or microbial antigens; or vascular endothelial dam- intake; (3) a decrease in complex carbohydrates and fiber; age) that involves leukocytes (eg, mast cells, eosinophils, (4) an increase in cereal grains and a decrease in and basophils, and neutrophils) as well as signaling molecules ; and (5) a decrease in protein, antioxidants, produced by these cells such as interleukins (eg, IL-1, IL- 15 and calcium intake.” (See Table 1.) 6), leukotrienes (eg, LTB4), and prostaglandins (eg, PGE2). Other inflammatory molecules are produced by FOOD AND INFLAMMATION the endothelium [eg, E-selectin, intercellular adhesion Inflammation is a dynamic, immune-mediated molecule 1 (ICAM-1) and vascular cell adhesion molecule 1 (VCAM-1)] and the [eg, C-reactive protein (CRP), TABLE 1 CONTENT OF PALEOLITHIC AND fibrinogen]. Additionally, the immune system requires WESTERN DIETS15-18, 21 reactive oxygen species (ROS) to kill pathogens, but these free radicals can also induce inflammation. All of these, as Dietary component Western diet Paleolithic well as other, inflammatory mediators are relatively short (calories/d) 3,900 ↓* lived and are part of the acute inflammatory response. In Protein 11 19-35 (% of total calories) this response, vessel diameter and permeability are Meat 12 (mostly conven- 45–60 (wild game)† altered, which permits plasma and leukocytes to (% of total calories) tionally raised beef ) migrate out of the blood vessel and into a lesion. Carbohydrates (% of 50 22-46 Chronic inflammation occurs when damage contin- total calories) ues and acute inflammatory mediators remain elevated or quality Mostly refined, Mostly complex, become elevated too often. This state is characterized by rapidly absorbed slowly absorbed an infiltration of mononuclear cells (lymphocytes and Refined sugars (kg/yr) 69.1 0 monocytes), inflammatory cell–mediated tissue destruc- Water, relative ↓ (mainly in _ consumption tion, and increased angiogenesis at the foci of active tissue containing soft 23 drinks) repair. A complete discussion of the pathology and bio- Fat, total (% total 39 21 (mostly unrefined, chemistry of inflammation is beyond the scope of this daily calories) plant based) paper; however, a partial list of inflammatory mediators is Saturated fat (% total 32 ↓ provided in Table 2. daily calories) Polyunsaturated-to- 0.67 1.41 saturated fat ratio TABLE 2 SOME INFLAMMATORY MEDIATORS Cholesterol (mg/day) 430 520 IL-1 trans fatty acids (g/day) 5.3 0 IL-6 Total long-chain 0.2 2.3 TNF-alpha omega-6 + omega-3 (g/day) Fibrinogen Ratio of omega 6:3 12 2.4 LTB4 Fiber (g/day) 24 100-150 PGE2 Fiber from vegetables 40 100 Cyclooxygenase-2 (COX-2) and (%) ICAM-1 Sodium (mg/day) 1,330 690 VCAM-1 K:Na 2.81 _ (Potassium intake CRP was 3 to 4 times high- er than today) Nuclear factor-_B Riboflavin mg/d 1.34-2.08 6.49 The influence of diet on inflammation results from a mg/d 0.149-0.205 0.357 combination of food quantity and quality, and genetic Thiamin mg/d 1.08-1.75 3.91 susceptibility. James O’Keefe, Jr, MD, of the Mid America mg/d 2.05-2.57 5.56 Heart Institute, co-authored a review article on the effects mg/d 7.02-8.48 17.2 diet has on . He concluded that it mg/d 77-109 440-604 results from a diet and lifestyle “at odds with our mg/d 7-10 32.8 Paleolithic genome.”16 Several features of the modern diet *Up and down arrows are used when exact numbers are not known, have been studied extensively for their effects on inflam- and denote relatively higher or lower amounts, respectively. †Conventionally-raised beef has a higher fat content than wild game, mation. Specifically, excessive consumption of refined and the fat in conventionally-raised beef has a relatively high omega-6 carbohydrates, low dietary fiber intake, and a high omega- to omega-3 ratio compared to wild game. 6 to omega-3 ratio are strongly associated with the pro-

Integrative Medicine • Vol. 5, No. 4 • Aug/Sept 2006 15 duction of pro-inflammatory molecules.24-26 Additionally, and levels of cholesterol than did controls. Total fruit, veg- antioxidants decrease inflammation, and the low intake of etable, nuts, and intakes, and oil con- antioxidants in the form of (eg, C and E) and sumption were also significantly higher.” Compared with found in fruits and vegetables contributes to a the control group, the group also had chronic, pro-inflammatory state that initiates, maintains, significantly greater improvement in all end points after and exacerbates disease.19,27,28 (See Table 3 for a list of the 2 years. In addition, only 40 patients in the dietary patterns or components and their relationship to Mediterranean diet group could still be classified as hav- inflammatory mediators.) ing at the end of the trial, compared In a cross-sectional study of 732 women (43-69 years with 78 volunteers in the control group (P<0.001). old, average 56 years) participating in the Nurses’ Health Among other reasons, diet can alter inflammatory Study, researchers analyzed the correlation between markers because of the quantity of food consumed, dietary patterns and inflammatory markers. Two dietary macronutrient and antioxidant content, glycemic load, patterns were identified using food frequency question- and fatty acid ratio. Due to the high quantity of low-fiber naires: the “prudent pattern” diet and the Western diet. processed foods in the Western diet, the glycemic load The prudent pattern diet was much closer to a Paleolithic (GL) of food is higher than in the Paleolithic or diet than the Western diet in that the prudent pattern diet Mediterranean diets. The GL indicates the relative effect a contained larger amounts of vegetables, fruit, , given quantity of food has on raising blood sugar. Unlike whole grains, , and . The Western diet pattern the (GI), which denotes how rapidly a car- in this cohort contained more , processed meat, bohydrate (eg, a ) turns into , the GL takes , sweets and other desserts, French fries, and into account how much carbohydrate might be in a given high-fat dairy products. Inflammatory markers showed a serving of the food, and, therefore, how eating a specific positive relation with the Western diet, including signifi- quantity of that food affects blood sugar. Thus, a high-GI cantly greater concentrations of CRP (P<0.001), IL-6 food, such as watermelon, may have a low GL if the person (P=0.006), E-selectin (P<0.001), sICAM-1 (P<0.001), and only eats a small serving. In diets containing refined foods sVCAM-1 (P=0.008) in the highest quintile of those fol- low in fiber, people typically consume large amounts of lowing the Western diet, compared with the lowest quin- high-GL foods. One result from this is blood fluctuations. tile. In comparison, there was a modest but statistically Recently, acute postprandial fluctuations in blood glucose significant decrease in these same inflammatory markers concentrations in patients with type 2 diabetes were in the highest quintile of the prudent pattern diet com- shown to result in greater generation of oxidative stress pared with the lowest quintile.29 than chronic, sustained .31 It is a sobering Similar to the prudent pattern diet, the comparison, since, in itself, hyperglycemia has such dele- Mediterranean diet stresses exercise, whole grains, fruits, terious effects because it produces ROS that damage mito- vegetables, legumes, and nuts.30 In a single, blind, 2-year chondria and activate nuclear factor kappa beta (NFkB), a clinical trial, 180 volunteers (mean age approximately 44 nuclear transcription factor involved in the production of years) diagnosed with metabolic syndrome were random- inflammatory mediators such as interleukins and TNF- ized to follow a Mediterranean diet (n=90) or a control alpha.32,33 Consuming , which is used to sweeten diet (n=90) containing 50% to 60% carbohydrates, 15% to soft drinks, can also increase free-radical generation.34 20% proteins, and less than 30% total fat. Volunteers in the Fat quality also plays a role in inflammation because Mediterranean diet group were given the same percent it is incorporated into cell membranes and affects cell-sig- recommendations as in the control group, but were also naling. Fatty acids are cleaved from the cell membrane by instructed to eat less than 10% saturated fat and less than phospholipase A2 (PLA2) and then metabolized to 300 mg/day cholesterol; to consume at least 250 to 300 prostaglandins or leukotrienes by either cyclooxygenase g/day fruits, 125 to 150 g/day vegetables, 25 to 50 g/day or lipoxygenase enzymes. The omega-6 series of fatty , and 400 g/day whole grains (defined in this acids, such as arachadonic acid (20:4 omega-6) are con- study as legumes, , , and wheat); and to increase verted by these enzymes into that are part of the consumption. End points, which included serum pro-inflammatory cascade, such as PGE2 and LTB4. In high-sensitivity C-reactive protein (hsCRP), IL-6, IL-7, and contrast, fatty acids in the omega-3 series, such as eicos- IL-18, were determined at baseline and after 2 years. apentaenoic acid (EPA, 20:5 omega-3), are metabolized by The researchers reported that after 2 years on the these enzymes into cytokines that are part of the anti- Mediterranean diet, volunteers “consumed a greater per- inflammatory cascade, such as prostaglandin I3 (PGI3) centage of calories from complex carbohydrates and from and thromboxane (TXA3). polyunsaturated and monounsaturated fat; had a greater The relative proportion of omega-6 and omega-3 intake of fiber; had a lower ratio of omega-6 to omega-3 fatty acids in tissues is modified by diet. High concentra- fatty acids; and had lower calories, levels of saturated fat, tions of omega-6 are found in red meat and dairy

16 Integrative Medicine • Vol. 5, No. 4 • Aug/Sept 2006 products, while omega-3 fatty acids are found in the high- nicians can help decrease the overwhelming burden of est quantities in nuts, vegetables, and fish. As already chronic degenerative diseases on our healthcare system by noted, the Western diet is high in omega-6 and low in educating and encouraging patients to move in the direc- omega-3 fatty acids, which contributes to a pro-inflamma- tion of better health through better diet (see Table 4). tory state. As levels of EPA increase in macrophages, pro- 35 duction of TNF-alpha and IL-1_ decrease. TABLE 4 Trans fatty acids, which are present in fried and many AND LIFESTYLE RECOMMENDATIONS16 processed foods, also contribute to inflammation. Using Eat whole, natural, fresh foods. data from the Nurses’ Health Study, Walter Willet, MD, showed 12 years ago in 1993 that trans fatty acid con- Consume a diet high in fruits, vegetables, nuts, and ; sumption increases the risk of CHD.36 In a follow-up to the and low in refined grains and sugars. Nurses’ Health Study, trans fat intake linearly correlated with plasma concentration of CRP (P=0.009). CRP was Increase consumption of omega-3 fatty acids from fish, , 73% higher among women in the highest quintile of trans and plant sources. fatty acid intake (3.7 ± 0.6 g/d) compared with those in Avoid all trans fats and limit intake of saturated fats. Eliminate 37 the lowest quintile (1.5 ± 0.3 g/d). fried foods, hard , commercial baked goods, and most packaged and processed snack foods. Substitute TABLE 3 DIETARY PATTERN OR COMPONENTS AND monounsaturated fats (eg, , nuts and ) and THEIR RELATIONSHIP TO INFLAMMATORY MEDIATORS polyunsaturated fats (eg, whole grains, fish—in particular her- ring, , mackerel, and —and ) for satu- Diet or dietary components Effects on inflammation rated fats (eg, red meats and high-fat dairy products). Western dietary pattern Associated with increased CRP, IL-6, E-selectin, sICAM-1, Increase consumption of lean protein, such as skinless poultry, sVCAM-129 fish, and game meats and lean cuts of red meat. Avoid high-fat Prudent pattern diet Associated with decreased CRP dairy and fatty, salty processed meats, such as bacon, sausage, and E-selectin29 and deli meats. Mediterranean diet Decreased CRP and IL-638 Incorporate olive oil into the diet. Trans fatty acids Associated with increased CRP37 Sugar-sweetened soft drink; Associated with increased CRP, Drink water. refined grains; processed meat; IL-6, E-selectin, sICAM-1, and diet soft drinks; vegetables other sVCAM-119 Participate in daily exercise through various activities (incorpo- than green leafy vegetables, yel- rating aerobic and strength training and stretching exercises). low vegetables, cruciferous veg- etables, tomatoes, and legumes Outdoor activities are ideal. , coffee, cruciferous Associated with decreased CRP, vegetables, yellow vegetables IL-6, E-selectin, sICAM-1, and John Neustadt, ND, is the founder of Montana Integrative Medicine in sVCAM-119 Bozeman, Mont. He is a member of the American Association of Omega-3 fatty acids Decreases TXA2, PGE2, TNF- Naturopathic Physicians’ Scientific Affairs Committee. Dr Neustadt has alpha, IL-1 beta.35 Associated written more than 100 published research reviews and is co-author, with with decreased TNF-alpha Jonathan Wright, MD, of Thriving through Dialysis (Auburn, Wash: Dragon receptor expression and CRP.25 Arts Publishing; 2006).

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