I am often asked what foods I avoid because they may carry a risk of contamination with pathogenic organisms.  I have a very short list of foods to avoid on principle based on concerns about the potential for bacterial adulteration.  But I am increasingly concerned about the general quality of the American diet as a cause of chronic health problems, including increasing rates of heart disease, obesity, and type 2 diabetes.  And while bacterial contamination of food in this country remains a large problem, in terms of disease burden it is dwarfed by the effects of unadulterated foods we eat every day. Most of us are aware that the number one killer of adult Americans is heart disease.  Cardiovascular heart disease is driven in significant part by what we eat.  In very simple terms, cardiovascular disease involves injury to the endothelial cells that line coronary arteries and leads to formation of fatty streaks which contain lipoproteins and other cellular debris.  Fat deposition also provokes an inflammatory reaction in the arterial walls which promotes further cellular deposition.[1] Rupture of these “plaques” is a leading cause of sudden coronary artery obstruction or heart attack and stroke.  In addition to high levels of cardiovascular heart disease, Americans also experience high levels of obesity, hypertension, and diabetes which are interrelated and all share roots in the American diet.  Indeed, current research indicates that obesity, glucose intolerance, and hypertension in childhood are strongly associated with increased rates of premature death from endogenous causes in adulthood.[2] Researchers have spent decades trying to tease out those factors that increase our risk of heart disease and related disorders.  For instance, The Framingham Heart Study[3] is the largest longitudinal study of cardiovascular heart disease ever conducted.  Starting with a cohort of just over 5,200 adult men and women in 1948 who lived in Framingham, Massachusetts, the Study continues to follow the now multi-generational cohort to identify, among other things, risk factors for cardiovascular heart disease.  Among the risk factors Framingham has traced are levels of lipoproteins, combinations of proteins, and lipids that transport fat in the bloodstream.  As the Framingham study makes clear, both low density liproproteins (LDL a/k/a “bad”[4] cholesterol) and high density lipoproteins (HDL a/k/a “good” cholesterol) play important roles in coronary artery disease. Perhaps because we’ve heard so much about cholesterol, Americans have long been focused on dietary fat as a risk for cardiovascular heart disease.  But what if there is an aspect of the American diet that poses a host of serious health effects, including cardiovascular heart disease, more deleterious than dietary fat (or additives, chemicals, or anything else on your food worry list)? In 1982 the USDA recommended that Americans reduce their intake of dietary fat by 10 percent.  This recommendation was based in significant part on an epidemiological study by famed University of Minnesota epidemiologist Ancel Keys, called the Seven Countries Study, that showed as dietary fat intake increased so did the incidence of heart disease.[5] And while we have, in fact, consumed less fat since, we are steadily consuming more calories and the rate of cardiovascular heart disease has not decreased.  Why?  An important part of the answer appears to be sugar, and specifically one type of sugar: fructose.   Table sugar, sucrose, is about half glucose and half fructose.  And while there are a variety of dietary sources of fructose, the biggest source in the American diet is high fructose corn syrup which sometimes has a higher concentration of fructose than does sucrose.[6] High fructose corn syrup is not natural.  It was invented in Japan in 1966 and made its way into the American diet beginning in the mid-1970s on the heels of sugar price supports enacted during the Nixon administration.   High fructose corn syrup has two attributes that make it appealing to food manufacturers: it is cheaper than sucrose and it easily handled and transported because it is a liquid.  Given its prevalence today in processed foods one could conclude that everything tastes a little better with some high fructose corn syrup in it.[7] Obese people do not want to be obese.  Americans have not consciously chosen to become fat en masse over the past few decades.  Something has been going on with the American diet to produce an increasing number of obese adults, teens, and yes, babies.[8] In an article published in the journal Obesity in 2006, researchers found children 6 years old and younger are 59 percent more likely to be overweight than they were in the 1980s.  Meanwhile, babies up to 6 months old are 74 percent more likely to be overweight.[9]  As we get fatter we also continue to suffer very high rates of cardiovascular heart disease and diabetes. One of things that is clearly going on is that Americans eat more of most everything and much, much more sugar than we did even a few decades ago.  Annual consumption of total sugars increased about 25 pounds from 1970 to 2000 and not coincidentally our consumption of corn sweeteners (mainly high fructose corn syrup) nearly tripled ruing that same period.[10] (Click to enlarge chart) Whatever else the USDA does, it collects a lot of data on what we eat through the Agricultural Research Service’s National Health and Nutrition Examination Survey (NHANES)[11] NHANES has documented the changing American diet in detail over the past decades including our increasing consumption of sugar. Our bodies literally run on sugar, glucose that is.  Glucose can be used by every cell in the body.  It is stored in the liver in the form of glycogen.  Fructose is metabolized by the liver very differently than glucose.  Unlike glucose only the liver can metabolize fructose which means all the fructose you eat goes straight to your liver where a number of distinctly deleterious actions occur.  For instance, fructose metabolism in the liver increases uric acid (which causes gout) and also inhibits the enzyme involved in nitric oxide production which is a vasodilator–something that keeps our blood vessels open and helps lower blood pressure.  Indeed, a high fructose diet is a recipe for hypertension.[12] Fructose metabolism has been implicated in hyperinsulinemia–a heightened insulin response which can interfere with the hormone leptin that tells us when we have had enough to eat.[13] Instead of promoting satiety, fructose consumption may actually increase food intake and obesity.[14] A high fructose diet is also associated with increased production of very low density liproproteins (VLDL)[15] high levels of which increase the risk for cardiovascular heart disease.[16] The consumption of high levels of fructose is the subject of much ongoing research which point to a role for the overconsumption of fructose in the metabolic syndrome.  The metabolic syndrome is a cluster of conditions–hypertension, elevated insulin levels, excess body fat around the waist, abnormal cholesterol levels, and dislipidemia[17]–that occur together, increasing your risk of heart disease, stroke, and diabetes.  Fructose appears to be highly lipogenic (causing fat formation) and contributes to tissue insulin insensitivity, metabolic defects, and the development of a prediabetic state.[18] If this sounds like a big deal, it ought to since we’re talking about the leading cause of death in the U.S. and conditions that dominate the economics of our health care system.  In one study medical students were fed either glucose or fructose to see how it affected de novo lipogenesis (new fat formation).  The results are illustrated in the chart below.[19] It indicates that a high sugar diet is really a high fat diet. The effects of a high sugar diet are compounded by the absence of fiber in what most of America eats.  If you eat highly processed foods, including fast food, you are consuming almost no fiber.  There are lots of claims about what fiber can and cannot do, but the consumption of fiber may play a role in fat formation by reducing the rate of intestinal carbohydrate absorption and reducing the insulin response; speeding transit of the contents of the intestine to the ileum which triggers satiety; and, inhibiting absorption of some free fatty acids.[20] It is no surprise that corn sweeteners are now the dominant form of sugar given the ubiquity of all things corn in the American diet.  There is little reason to believe that the FDA will take action to protect Americans from their overconsumption of corn sweeteners since it has failed to meaningfully regulate high fructose corn syrup.   But the evidence that too much fructose is dangerous is hard to dismiss.  A recent study on human subjects, in which two groups were given either glucose- or fructose-sweetened beverages, suggests differences in the way these sugars affected fat deposition:  “…fructose and glucose have differential effects on regional adipose distribution. We believe that these results are novel and warrant further investigation.”[21] This study also found an association between fructose consumption and decreased insulin sensitivity, one of the pathways to diabetes.  A diet that leads to chronic health problems such as diabetes also makes one more vulnerable to infection, including foodborne pathogens.[22] Likewise, it appears that obesity itself may alter the immune response and increase vulnerability to common infections.[23] What does this all mean?  Consider this comment about the future impact of the growing waistlines of adolescent Americans from a study that projected the annual increase in the incidence of cardiovascular heart disease secondary to obesity:  “Although projections 25 or more years into the future are subject to innumerable uncertainties, extrapolation from current data suggests that adolescent overweight will increase rates of cardiovascular heart disease among future young and middle-aged adults, resulting in substantial morbidity and mortality“[24] (emphasis added). Young Americans may well be eating their way to sugary graves.  Current research suggests that the single most dangerous thing in the American diet may well be too much sugar.[25] And whether you are young or old, that is food for thought indeed. References: 1.  http://www.texasheart.org/hic/topics/cond/vulplaq.cfm. 2.  Franks PW et al.  Childhood Obesity, Other Cardiovascular Risk Factors, and Premature Death.  NEJM, vol. 362:485-493 (February 11, 2010). 3.  http://www.framinghamheartstudy.org/. 4.  Size and density matters with cholesterol.  Small, dense cholesterol particles are more likely to penetrate arterial walls where they help build plagues.  Not all LDL is the same however.  Some LDL, known as pattern A, is relatively larger and less dense and is considered benign in terms of CVD risk.   And certainly some component of cholesterol make up in any individual is driven by genetics. 5.  Verschuren WM et al. Serum total cholesterol and long-term coronary heart disease mortality in different cultures. Twenty-five-year follow-up of the seven countries study.  JAMA. 1995 Jul 12;274(2):131-6.  This review, and many other commentaries, makes clear that the association between high dietary fat intake and Cardiovascular heart disease is dependent on more than just fat.  Indeed, Americans’ declining fat consumption and associated high rates of cardiovascular heart disease have prodded research increasingly towards carbohydrates as a key contributing factor to a variety of maladies. 6. High fructose corn syrup contains 42 to 55 percent fructose; 55 percent high fructose corn syrup is typically used in soft drinks. It is not high fructose corn syrup per se that constitutes the problem of increased sugar and caloric consumption in the American diet.  But high fructose corn syrup is the form in which we get most of our fructose, and too much fructose is a problem.  You may have noticed that the Corn Refiners Association is running an extensive TV ad campaign that seeks to convey the “naturalness” of high fructose corn syrup.  See www.sweetsurprise.com.  Of course, high fructose corn syrup does not occur in nature.   Fructose is a natural component of fruit, but it would be very hard to over consume fructose solely by eating fruit; fruit juice, on the other hand, is a significant source of fructose for many American children. 7.  A review of ingredient labels of “low fat” food items typically reveals that the fat has been replaced by high fructose corn syrup. 8.  Kim J et al. Trends in Overweight from 1980 through 2001 among Preschool-Aged Children Enrolled in a Health Maintenance Organization. OBESITY (2006) 14, 1107-1112; see also, Gillman, MW, The first months of life: a critical period for development of obesity.  American Journal of Clinical Nutrition, Vol. 87, No. 6, 1587-1589, June 2008. 9.  Kim J, supra. 10.  USDA Agricultural Fact Book 2001-2002, Chapter 2 Profiling Food Consumption in America, table 2-6. 11.  http://www.ars.usda.gov/Services/docs.htm?docid=13793. 12.  Nguyen S, et al. Sugar-Sweetened Beverages, Serum Uric Acid, and Blood Pressure in Adolescents.  J PEDIATRICS, vol. 154, Issue 6:783-784, June 2009.  See also, Johnson RJ, et al, Potential role of sugar (fructose) in the epidemic of hypertension, obesity and the metabolic syndrome, diabetes, kidney disease, and cardiovascular disease.  AM J CLIN NUTRI, Vol. 86, No. 4, 899-906, October 2007.  See also, Jalal DI et al , Increased Fructose Intake Is Independently Associated with Elevated Blood Pressure. Findings from the National Health and Nutrition Examination Survey (2003-2006). J AM SOC NEPHROL, 20:9A November 2009. 13.  Lustig RH. Childhood obesity: behavioral aberration or biochemical drive? Reinterpreting the First Law of Thermodynamics.  Nature Clinical Practice Endocrinology & Metabolism, 2:447-458 (2006). 14.  Lane MD, Cha SH. Effect of glucose and fructose on food intake via malonyl-CoA signaling in the brain.  Biochem Biophys Res Commun. 24;382(1):1-5 (April 2009). Epub 2009 Mar 3.  But see, Moran, TH. Fructose and satiety. J Nutr. 2009 Jun;139(6):1253S-1256S (“On balance, the case for fructose being less satiating than glucose or high fructose corn syrup being less satiating than sucrose is not compelling”). 15.  Chong MFF. Mechanisms for the acute effect of fructose on postprandial lipemia.  AM J CLINICAL NUTRI, Vol. 85, No. 6, 1511-1520, June 2007. 16.  Liu J. Non-high-density lipoprotein and very-low-density lipoprotein cholesterol and their risk predictive values in coronary heart disease.  AM J CARDIOL. 15;98(10):1363-8 (Nov 2006. 17.  Dyslipidemia is the dysfunction of lipoprotein metabolism involving elevated cholesterol, high triglycerides, elevated levels of LDL and low HDL.  It is associated with an increased risk of coronary heart disease. 18.  Miller A. Dietary Fructose and the Metabolic Syndrome.  CURR OPIN GASTROENTEROL, 24(2):204-9, March 2008. 19.  Hellerstein et al. Regulation of de novo lipogenesis in humans. ANN REV NUTR 16:523, 1996. 20.  See, e.g., Mathern JF, et al. Effect of fenugreek fiber on satiety, blood glucose and insulin response and energy intake in obese subjects.  PHYTOTHER RES., 23(11):1543-8, November 2009. 21.  Stanhope KL, et al. Consuming fructose-sweetened, not glucose-sweetened, beverages increases visceral adiposity and lipids and decreases insulin sensitivity in overweight/obese humans.  J CLIN INVEST.; 119(5): 1322-1334 (May 2009). 22.  http://www.mayoclinic.com/health/food-poisoning/DS00981/DSECTION=risk-factors 23.  Falagas ME, Obesity and Infection. LANCET INFECT DIS., 6(7):438-46 (July 2006). 24.  Bibbons-Domingo K, et al. Adolescent Overweight and Future Adult Coronary Heart Disease.  NEJM, Volume 357:2371-2379, December 2007. 25.  It is important to note that many studies, as well as common experience, have found a significant role for lower levels of physical activity in Americans’ growing waistlines.  As with most complex health problems no single factor can be blamed for all effects, but the focus of this article is on caloric intake not expenditure.