As asked, I've investigated the research on fructose further, but I'm not sure how applicable it is to the paleo diet with fruit. (I've omitted the results relating to dental problems, gut intolerance and allergies.) The results are also limited to human studies and English language. If you have a specific disease or physiological process you would like me to research further, let me know. From the results, it looks like Dr. Richard Bernstein is correct in advising diabetics to limit or avoid fruit. Authors Teff KL. Elliott SS. Tschop M. Kieffer TJ. Rader D. Heiman M. Townsend RR. Keim NL. D'Alessio D. Havel PJ. Institution Monell Chemical Senses Center, University of Pennsylvania, Philadelphia 19104, USA. Title Dietary fructose reduces circulating insulin and leptin, attenuates postprandial suppression of ghrelin, and increases triglycerides in women. Source Journal of Clinical Endocrinology & Metabolism. 89(6):2963-72, 2004 Jun. Abstract Previous studies indicate that leptin secretion is regulated by insulin-mediated glucose metabolism. Because fructose, unlike glucose, does not stimulate insulin secretion, we hypothesized that meals high in fructose would result in lower leptin concentrations than meals containing the same amount of glucose. Blood samples were collected every 30-60 min for 24 h from 12 normal-weight women on 2 randomized days during which the subjects consumed three meals containing 55, 30, and 15% of total kilocalories as carbohydrate, fat, and protein, respectively, with 30% of kilocalories as either a fructose-sweetened [high fructose (HFr)] or glucose-sweetened [high glucose (HGl)] beverage. Meals were isocaloric in the two treatments. Postprandial glycemic excursions were reduced by 66 +/- 12%, and insulin responses were 65 +/- 5% lower (both P < 0.001) during HFr consumption. The area under the curve for leptin during the first 12 h (-33 +/- 7%; P < 0.005), the entire 24 h (-21 +/- 8%; P < 0.02), and the diurnal amplitude (peak - nadir) (24 +/- 6%; P < 0.0025) were reduced on the HFr day compared with the HGl day. In addition, circulating levels of the orexigenic gastroenteric hormone, ghrelin, were suppressed by approximately 30% 1-2 h after ingestion of each HGl meal (P < 0.01), but postprandial suppression of ghrelin was significantly less pronounced after HFr meals (P < 0.05 vs. HGl). Consumption of HFr meals produced a rapid and prolonged elevation of plasma triglycerides compared with the HGl day (P < 0.005). Because insulin and leptin, and possibly ghrelin, function as key signals to the central nervous system in the long-term regulation of energy balance, decreases of circulating insulin and leptin and increased ghrelin concentrations, as demonstrated in this study, could lead to increased caloric intake and ultimately contribute to weight gain and obesity during chronic consumption of diets high in fructose. Authors Vasdev S. Longerich L. Gill V. Institution Faculty of Medicine, Memorial University of Newfoundland, St. John's, Newfoundland, Canada. [log in to unmask] Title Prevention of fructose-induced hypertension by dietary vitamins. [Review] [124 refs] Source Clinical Biochemistry. 37(1):1-9, 2004 Jan. Abstract Essential hypertension in humans may develop through a combination of genetic and environmental factors. Diet has long been under investigation as a potential effector of blood pressure. A diet high in sucrose or fructose can give rise to hyperlipidemia, insulin resistance and hypertension. Insulin resistance, glucose intolerance and oxidative stress are common features of hypertension. If glucose metabolism through the glycolytic pathway is impaired, as in insulin resistance, there will be a build-up of glyceraldehyde, glyceraldehyde-3-phosphate and dihydroxyacetone phosphate with further metabolism to methylglyoxal, a highly reactive ketoaldehyde. Excess aldehydes can bind sulfhydryl groups of membrane proteins, altering membrane calcium channels, increasing cytosolic free calcium, peripheral vascular resistance and blood pressure. The presence of reactive aldehydes can also lead to oxidative stress. Dietary management through lower sucrose or fructose intake and increas! ed consumption of vitamins improves glucose metabolism, lowers tissue aldehydes, increases anti-oxidant capacity and may also prevent hypertension. [References: 124] Authors Pickering TG. Institution The Zena and Michael A. Wiener Cardiovascular Institute, Mt. Sinai School of Medicine, 50 East 98th Street, New York, NY 10029-6574, USA. Title America the fat: fast food and fructose. Source Journal of Clinical Hypertension. 5(4):298-9, 2003 Jul-Aug. Authors Elliott SS. Keim NL. Stern JS. Teff K. Havel PJ. Institution Department of Nutrition, University of California, Davis 95616, USA. Title Fructose, weight gain, and the insulin resistance syndrome.[see comment]. [Review] [134 refs] Source American Journal of Clinical Nutrition. 76(5):911-22, 2002 Nov. Abstract This review explores whether fructose consumption might be a contributing factor to the development of obesity and the accompanying metabolic abnormalities observed in the insulin resistance syndrome. The per capita disappearance data for fructose from the combined consumption of sucrose and high-fructose corn syrup have increased by 26%, from 64 g/d in 1970 to 81 g/d in 1997. Both plasma insulin and leptin act in the central nervous system in the long-term regulation of energy homeostasis. Because fructose does not stimulate insulin secretion from pancreatic beta cells, the consumption of foods and beverages containing fructose produces smaller postprandial insulin excursions than does consumption of glucose-containing carbohydrate. Because leptin production is regulated by insulin responses to meals, fructose consumption also reduces circulating leptin concentrations. The combined effects of lowered circulating leptin and insulin in individuals who consume diets that are high in dietary fructose could therefore increase the likelihood of weight gain and its associated metabolic sequelae. In addition, fructose, compared with glucose, is preferentially metabolized to lipid in the liver. Fructose consumption induces insulin resistance, impaired glucose tolerance, hyperinsulinemia, hypertriacylglycerolemia, and hypertension in animal models. The data in humans are less clear. Although there are existing data on the metabolic and endocrine effects of dietary fructose that suggest that increased consumption of fructose may be detrimental in terms of body weight and adiposity and the metabolic indexes associated with the insulin resistance syndrome, much more research is needed to fully understand the metabolic effect of dietary fructose in humans. [References: 134] Authors Howard BV. Wylie-Rosett J. Title Sugar and cardiovascular disease: A statement for healthcare professionals from the Committee on Nutrition of the Council on Nutrition, Physical Activity, and Metabolism of the American Heart Association.[see comment][erratum appears in Circulation. 2003 Apr 29;107(16)2166]. Source Circulation. 106(4):523-7, 2002 Jul 23.