Endocrine and Metabolic EffectsHepatic Fructose Metabolism (Havel, Nutr. Rev., 2005) Plasma Glucose...

Metabolic and Endocrine Effects of Consuming Beverages Sweetened with Glucose, Fructose, Sucrose, and HFCS

(Just the Data and Potential Mechanisms)

Peter J. Havel DVM, PhDProfessor, Department of Molecular Biosciences

School of Veterinary Medicineand Department of Nutrition

University of California, Davis

National Lipid AssociationScottsdale, AZ, June 2, 2012

Consuming High Fructose Meals Reduces 24 Hour Insulin and Leptin Concentrations, does

not Suppress Ghrelin, and Increases Triglycerides in Women

Karen Teff, David A. D’Alessio, Matthias Tschoep, Mark Heiman, Timothy Keiffer, Raymond Townsend,

Daniel Rader, Nancy L. Keim, and Peter J. Havel

GCRC, University of Pennsylvania, Eli Lilly, University of Alberta, USDA Western Human Nutrition Research Center and

University of California, Davis

Supported by ILSI-NA, and NIH Grant: DK-58108J. Clin. Endocrinol. Metab., 2004

40

60

80

100

120

[TR

IGL

YC

ER

IDE

S]

(mg

/dl)

TIME (h)

9:00 AMBreakfast

1:00 PMLunch

6:00 PMDinner

0800 1200 1600 2000 2400 0400 0800

Plasma Triglycerides Were Elevated After HighFructose Compared with High Glucose Meals

HIGH GLUCOSE

HIGH FRUCTOSE

Teff et al, JCEM, 2004

Teff et al, JCEM, 2009

Teff et al, JCEM, 2009

Plasma Glucose or Fructose Concentrations during Saline, Glucose or Fructose (15 mg/kg/min) Infusion in 9 rhesus monkeys

Adams et al, Endocrinology, 2008

Hepatic Fructose Metabolism (Havel, Nutr. Rev., 2005)

Plasma Glucose or Fructose Concentrations in Subjects Consuming Sugar-Sweetened Beverages (Teff et al, JCEM, 2009)

SH Adams et al, Endocrinology, 2008

Twenty-four Hour Endocrine and Metabolic Profiles Following Consumption of High

Fructose Corn Syrup-, Sucrose-, Fructose-, and Glucose-Sweetened Beverages with

Meals in Normal Weight and Overweight/Obese Men and Women

Kimber L. Stanhope, Steven C. Griffen, Brandi R. Bair, Michael Swarbrick, Nancy L. Keim,

and Peter J. Havel

Stanhope et al, Am. J. Clin. Nutr., 2008Funded in part by Pepsico, Inc.

BACKGROUND

It had been proposed that high fructose corn syrup (HFCS) differs from sucrose and has unique obesity-promoting properties.

In addition, the increased use of HFCS coincides with the increase of obesity in the U.S., but not necessarily elsewhere in the world (e.g. Mexico and Australia).

However, HFCS (42-55% fructose) and sucrose (50% fructose) are quite similar in their fructose content (although up to 65% in one report (Goran et al, Obesity, 2011).

Nonetheless, there were no studies directly comparing the effects of HFCS and sucrose.

Stanhope et al, AJCN, 2008

Stanhope et al, AJCN, 2008

Stanhope et al, J. Clin. Invest., 2009

Stanhope,Ann. Rev. Med,2012

Stanhope et al, J. Clin. Invest., 2009

Conclusions:The consumption of fructose, but not glucose-sweetened beverages at 25% of energy requirements for 10 weeks increased visceral adiposity, produced unfavorable changes in a number of lipid parameters, and decreased insulin sensitivity in older overweight/obese men and women.

These differential effects were seen despite comparable weight gain in the two groups.

Potential MechanismGlycemic Index of the Diets

(Differing postprandial glucose/insulin responses)

Baseline (Complex CHO) Diet: GI = 64

Fructose Beverage Diet: GI = 38

Glucose Beverage Diet: GI = 83

Stanhope et al, AJCN, 2010

Stanhope et al, AJCN, 2010

Other Potential Mechanisms Underlying the Effects of Fructose to Increase Lipids and Lower Insulin Sensitivity:

• Increased hepatic de novo lipogenesis?• Decreased fat oxidation?

• Increases of free fatty acids (FFA)?• Increased uric acid (linked to met syn)?• Inflammation?• Hepatic triglyceride deposition (NAFL)?

Stanhope et al, J. Clin. Invest, 2009

Cox et al, Eur. J. Clin. Nutr., 2011

Cox et al, Eur. J. Clin. Nutr., 2011

Effects of 10 Weeks of Fructose or Glucose Consumption on Markers of Inflammation

Cox et al, J. Clin. Endocrinol. Metab., 2011

Potential Mechanisms in the Effects of Fructose to Increase Lipids and Lower Insulin Sensitivity:

• Meal-related glucose and insulin excursions (glycemic index/load) (No)

• Hepatic de novo lipogenesis (Yes, and FAOx)

• Increases of free fatty acids (No, systemic FFA is not increased)

• Increases of uric acid (Unlikely, circulating UA effects are small, possible role for intracellular UA)

• Inflammation (Possibly, Some indices are increased)

• Hepatic triglyceride deposition (In Progress)

Stanhope et al, J. Clin. Invest, 2009

NEW FRUCTOSE STUDY (Ongoing):

Dose-response study of the effects of fructose and HFCS consumption at 10%, 17.5%, and 25% of energy requirements with an ad libitum diet on 24 hour lipid profiles, insulin sensitivity/glucose tolerance, hepatic lipid deposition (MRI), and inflammation in normal weight overweight/obese men and women (aged 18-40 years). We are also studying subjects consuming sucrose.

Funded by NIH HL-091333 and HL- (2008-2015)

Changes of fasting lipids after 2 weeks of consuming glucose, fructose or HFCS sweetened beverages

Conclusions: Consumption of HFCS or fructose at 25% of energy requirements results in comparable increases of LDL cholesterol, ApoB and the ApoB/ApoA1 ratio within only 2 weeks in young (18-40 year old) men and women, independent of any changes of body weight/adiposity.

These effects are not seen with glucose-sweetened beverages.

Other levels of sugar consumption, effects of sucrose, lipid kinetics with stable isotopes and hepatic imaging are being conducted.

Funded by NIH HL-091333 and HL- (2008-2015)

Colleagues who have contributed to this workKimber L. Stanhope James GrahamAndrew Bremer Ronald KraussMaria Moreno Aliaga Steven GriffenNancy Keim Karen TeffLars Berglund Sean AdamsMichael Swarbrick Carine BeysenFrancine Gregoire David D’AlessioBethany Cummings Marc HellersteinJean-Marc Schwartz Chad CoxErnst Schaeffer Matthias TschopJanet King Katsuo Nakajima and colleagues