Fructose and the link to the metabolic syndrome - di Piero Portincasa e
Leonilde Bonfrate. 31 maggio 2012. Corso di formazione "valore nutrizionale e salutistico di prodotti agroalimentari” - Università degli studi di Bari.
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Fructose and the link to the metabolic syndrome - di Piero Portincasa e Leonilde Bonfrate
1. Fructose and the link to the metabolic
syndrome
Piero Portincasa, MD, PhD
Leonilde Bonfrate,MD
Department of Internal and Public Medicine
University of Bari Medical School
Bari – Italy
p.portincasa@semeiotica.uniba.it
2. NAFLD: Associated with Metabolic Syndrome
17/09/12
Metabolic Syndrome
Obesity
P. Portincasa, UNIBA
Diabetes
Dyslipidemia
EPIDEMIA DEL III MILLENNIO
6. 6
P. 17/09/1
Portincasa, 2
FRUITS AND VEGETABLES
UNIBA
•
Consumption is inversely related to the risk of coronary
heart disease (CHD) and stroke
The effect of fruit and vegetable intake on risk for coronary heart disease. AU
Joshipura KJ; Hu FB; Manson JE; Stampfer MJ; Rimm EB; Speizer FE; Colditz G;
Ascherio A; Rosner B; Spiegelman D; Willett WC SO Ann Intern Med 2001 Jun
19;134(12):1106-14.
Legume consumption and risk of coronary heart disease in US men and women:
NHANES I Epidemiologic Follow-up Study. AU Bazzano LA; He J; Ogden LG; Loria C;
Vupputuri S; Myers L; Whelton PK SO Arch Intern Med 2001 Nov 26;161(21):2573-8.
7. 7
P. 17/09/1
Portincasa, 2
The effect of fruit and vegetable intake on risk for coronary heart disease. AU Joshipura KJ; Hu FB;
UNIBA
Manson JE; Stampfer MJ; Rimm EB; Speizer FE; Colditz G; Ascherio A; Rosner B; Spiegelman D;
Willett WC SO Ann Intern Med 2001 Jun 19;134(12):1106-14.
•
The Nurses' Health Study and the Health Professionals' Follow-Up
Study
•
84 251 women 34 to 59 yrs of age who for 14 yrs and 42 148 men 40 to
75 yrs followed for 8 yrs
•
Incidence of nonfatal myocardial infarction or fatal coronary heart
disease (1127 cases in women and 1063 cases in men).
•
Diet assessed by using food-frequency questionnaires
•
CONCLUSIONS: Consumption of fruits and
vegetables, particularly green leafy vegetables and
vitamin C-rich fruits and vegetables, appears to have a
8. 8
P. 17/09/1
Portincasa, 2
Fruit and vegetable consumption and stroke: meta-analysis
UNIBA of
cohort studies. He FJ; Nowson CA; MacGregor GA Lancet. 2006
Jan 28;367(9507):320-6.
•
MEDLINE, EMBASE, the Cochrane Library, and bibliographies
of retrieved articles
•
8 studies, 9 independent cohorts
•
257,551 individuals (4917 stroke events), average follow-up of 13
years
•
relative risk of stroke was 0.89 (95% CI 0.83-0.97) for those
with 3 to 5 servings per day, and 0.74 (0.69-0.79) >5 servings
per day.
•
Fruit and vegetables significant protective effect on both
ischaemic and haemorrhagic stroke.
9. 9
P. 17/09/1
Portincasa, 2
UNIBA
Lyn M Steffen Jan 28, 2006, The Lancet, Vol. 367 No. 9507 pp 278-279
10. 10
P. 17/09/1
Portincasa, 2
UNIBA
5 a day!
Lancet. 2006 Jan 28;367(9507):320-6.
13. Dietary fructose
monosaccharide
Fructose
• a free hexose
• as the disaccharide (sucrose:
glucose-fructose)
• in a polymerized form (fructans)
Up to one half of the population
unable to completely absorb a
sucrose
load of 25 g
4 Kcal / g
Glycemic index: 23 (sucrose:
57)
14. According to the USDA database, foods with more fructose than glucose include:
Fructose (grams / Glucose (grams /
Food
100 grams) 100 grams)
High fructose
55 to 90 45 to 10
corn syrup
Sucrose
50 50
(for reference)
Honey 40.9 35.7
Raisins 29.8 27.8
Pears 6.2 2.8
Apples 5.9 2.4
Fruit juice
e.g. Apples, 5 to 7 2 to 3
Pears
Watermelon 3.4 1.6
16. Central administration of fructose
Fructose exerts an orexigenic effect
Seung Hun Cha et al., Proc Natl Acad Sci U S A. November 2008
17. The brain, like the liver, possesses a unique set of
enzymes that enables fructose to bypass the rate-
limiting step in glycolysis and thereby rapidly deplete
ATP in the hypothalamus
The central administration of fructose rapidly lowers
ATP, increases P-AMPK and P-ACC (acetyl-CoA
carboxylase ), and decreases malonyl-CoA in the
hypothalamus, whereas centrally administered glucose
has the inverse effects.
18. FRUCTOSE IN THE LIVER
A high flux of fructose to the liver (the main organ
capable of metabolizing this simple carbohydrate)
1. perturbs glucose metabolism and glucose uptake
pathways (Fructose-induced insulin resistance)
2. leads to a significantly enhanced rate of de novo
lipogenesis and triglyceride (TG) synthesis, driven
by the high flux of glycerol and acyl portions of TG
molecules from fructose catabolism.
NAFLD: Associated with Metabolic Syndrome NAFLD is associated with the metabolic syndrome. The metabolic syndrome is a constellation of disorders, including obesity, type 2 diabetes and dyslipidemia, that often cluster together. The prevalence of insulin resistance is very high in individuals with the metabolic syndrome. Marchesini G, Bugianesi E, Forlani G, Cerrelli F, Lenzi M, Manini R, Natale S, et al. Nonalcoholic fatty liver, steatohepatitis, and the metabolic syndrome. Hepatology 2003;37:917-923. Shirai K. Obesity as the core of the metabolic syndrome and the management of coronary heart disease. Curr Med Res Opin 2004;20:295-304. Miller JL. Insulin resistance syndrome. Description, pathogenesis, and management. Postgrad Med 2003;Spec No:27-34.
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2 TI The effect of fruit and vegetable intake on risk for coronary heart disease. AU Joshipura KJ; Hu FB; Manson JE; Stampfer MJ; Rimm EB; Speizer FE; Colditz G; Ascherio A; Rosner B; Spiegelman D; Willett WC SO Ann Intern Med 2001 Jun 19;134(12):1106-14. BACKGROUND: Many constituents of fruits and vegetables may reduce the risk for coronary heart disease, but data on the relationship between fruit and vegetable consumption and risk for coronary heart disease are sparse. OBJECTIVE: To evaluate the association of fruit and vegetable consumption with risk for coronary heart disease. DESIGN: Prospective cohort study. SETTING: The Nurses' Health Study and the Health Professionals' Follow-Up Study. PARTICIPANTS: 84 251 women 34 to 59 years of age who were followed for 14 years and 42 148 men 40 to 75 years who were followed for 8 years. All were free of diagnosed cardiovascular disease, cancer, and diabetes at baseline. MEASUREMENTS: The main outcome measure was incidence of nonfatal myocardial infarction or fatal coronary heart disease (1127 cases in women and 1063 cases in men). Diet was assessed by using food-frequency questionnaires. RESULTS: After adjustment for standard cardiovascular risk factors, persons in the highest quintile of fruit and vegetable intake had a relative risk for coronary heart disease of 0.80 (95% CI, 0.69 to 0.93) compared with those in the lowest quintile of intake. Each 1-serving/d increase in intake of fruits or vegetables was associated with a 4% lower risk for coronary heart disease (relative risk, 0.96 [CI, 0.94 to 0.99]; P = 0.01, test for trend). Green leafy vegetables (relative risk with 1-serving/d increase, 0.77 [CI, 0.64 to 0.93]), and vitamin C-rich fruits and vegetables (relative risk with 1-serving/d increase, 0.94 [CI, 0.88 to 0.99]) contributed most to the apparent protective effect of total fruit and vegetable intake. CONCLUSIONS: Consumption of fruits and vegetables, particularly green leafy vegetables and vitamin C-rich fruits and vegetables, appears to have a protective effect against coronary heart disease. AD Harvard School of Public Health, 677 Huntington Avenue, Boston, MA 02115, USA. PMID 11412050 3 TI Legume consumption and risk of coronary heart disease in US men and women: NHANES I Epidemiologic Follow-up Study. AU Bazzano LA; He J; Ogden LG; Loria C; Vupputuri S; Myers L; Whelton PK SO Arch Intern Med 2001 Nov 26;161(21):2573-8. BACKGROUND: Soybean protein and dietary fiber supplementation reduce serum cholesterol in randomized controlled trials. Consumption of legumes, which are high in bean protein and water-soluble fiber, may be associated with a reduced risk of coronary heart disease (CHD). METHODS: A total of 9632 men and women who participated in the First National Health and Nutrition Examination Survey Epidemiologic Follow-up Study (NHEFS) and were free of cardiovascular disease (CVD) at their baseline examination were included in this prospective cohort study. Frequency of legume intake was estimated using a 3-month food frequency questionnaire, and incidence of CHD and CVD was obtained from medical records and death certificates. RESULTS: Over an average of 19 years of follow-up, 1802 incident cases of CHD and 3680 incident cases of CVD were documented. Legume consumption was significantly and inversely associated with risk of CHD (P =.002 for trend) and CVD (P =.02 for trend) after adjustment for established CVD risk factors. Legume consumption 4 times or more per week compared with less than once a week was associated with a 22% lower risk of CHD (relative risk, 0.78; 95% confidence interval, 0.68-0.90) and an 11% lower risk of CVD (relative risk, 0.89; 95% confidence interval, 0.80-0.98). CONCLUSIONS: Our study indicates a significant inverse relationship between legume intake and risk of CHD and suggests that increasing legume intake may be an important part of a dietary approach to the primary prevention of CHD in the general population. AD Department of Epidemiology, Tulane University School of Public Health and Tropical Medicine, 1430 Tulane Ave, SL18, New Orleans, LA 70112, USA. jhe@tulane.edu PMID 11718588
2 TI The effect of fruit and vegetable intake on risk for coronary heart disease. AU Joshipura KJ; Hu FB; Manson JE; Stampfer MJ; Rimm EB; Speizer FE; Colditz G; Ascherio A; Rosner B; Spiegelman D; Willett WC SO Ann Intern Med 2001 Jun 19;134(12):1106-14. BACKGROUND: Many constituents of fruits and vegetables may reduce the risk for coronary heart disease, but data on the relationship between fruit and vegetable consumption and risk for coronary heart disease are sparse. OBJECTIVE: To evaluate the association of fruit and vegetable consumption with risk for coronary heart disease. DESIGN: Prospective cohort study. SETTING: The Nurses' Health Study and the Health Professionals' Follow-Up Study. PARTICIPANTS: 84 251 women 34 to 59 years of age who were followed for 14 years and 42 148 men 40 to 75 years who were followed for 8 years. All were free of diagnosed cardiovascular disease, cancer, and diabetes at baseline. MEASUREMENTS: The main outcome measure was incidence of nonfatal myocardial infarction or fatal coronary heart disease (1127 cases in women and 1063 cases in men). Diet was assessed by using food-frequency questionnaires. RESULTS: After adjustment for standard cardiovascular risk factors, persons in the highest quintile of fruit and vegetable intake had a relative risk for coronary heart disease of 0.80 (95% CI, 0.69 to 0.93) compared with those in the lowest quintile of intake. Each 1-serving/d increase in intake of fruits or vegetables was associated with a 4% lower risk for coronary heart disease (relative risk, 0.96 [CI, 0.94 to 0.99]; P = 0.01, test for trend). Green leafy vegetables (relative risk with 1-serving/d increase, 0.77 [CI, 0.64 to 0.93]), and vitamin C-rich fruits and vegetables (relative risk with 1-serving/d increase, 0.94 [CI, 0.88 to 0.99]) contributed most to the apparent protective effect of total fruit and vegetable intake. CONCLUSIONS: Consumption of fruits and vegetables, particularly green leafy vegetables and vitamin C-rich fruits and vegetables, appears to have a protective effect against coronary heart disease. AD Harvard School of Public Health, 677 Huntington Avenue, Boston, MA 02115, USA. PMID 11412050 3
TI Fruit and vegetable consumption and stroke: meta-analysis of cohort studies. AU He FJ; Nowson CA; MacGregor GA SO Lancet. 2006 Jan 28;367(9507):320-6. BACKGROUND: Increased consumption of fruit and vegetables has been shown to be associated with a reduced risk of stroke in most epidemiological studies, although the extent of the association is uncertain. We quantitatively assessed the relation between fruit and vegetable intake and incidence of stroke in a meta-analysis of cohort studies. METHODS: We searched MEDLINE, EMBASE, the Cochrane Library, and bibliographies of retrieved articles. Studies were included if they reported relative risks and corresponding 95% CIs of stroke with respect to frequency of fruit and vegetable intake. FINDINGS: Eight studies, consisting of nine independent cohorts, met the inclusion criteria. These groups included 257,551 individuals (4917 stroke events) with an average follow-up of 13 years. Compared with individuals who had less than three servings of fruit and vegetables per day, the pooled relative risk of stroke was 0.89 (95% CI 0.83-0.97) for those with three to five servings per day, and 0.74 (0.69-0.79) for those with more than five servings per day. Subgroup analyses showed that fruit and vegetables had a significant protective effect on both ischaemic and haemorrhagic stroke. INTERPRETATION: Increased fruit and vegetable intake in the range commonly consumed is associated with a reduced risk of stroke. Our results provide strong support for the recommendations to consume more than five servings of fruit and vegetables per day, which is likely to cause a major reduction in strokes. AD Blood Pressure Unit, Cardiac and Vascular Sciences, St George's University of London, London, UK. fhe@sgul.ac.uk PMID 16443039
. These observations have implications for dietary recommendations in patients in whom fructose malabsorption is suspected since foods that contain fructose may be well tolerated if they also contain glucose but may be less well tolerated if they also contain sorbitol (although sorbitol itself can cause diarrhea). Thus, it is the net amount of fructose that is important. . These observations have implications for dietary recommendations in patients in whom fructose malabsorption is suspected since foods that contain fructose may be well tolerated if they also contain glucose but may be less well tolerated if they also contain sorbitol (although sorbitol itself can cause diarrhea). Thus, it is the net amount of fructose that is important.
Metabolic pathways of entry of (A) glucose and (B) fructose into the glycolytic pathway of the CNS. GK, glucokinase; KHK, ketohexokinase; DHAP, dihypoxyacetone; Gald, glyceraldehyde.
J Hepatol. 2008 June; 48(6): 993–999. Published online 2008 March 10. doi: 10.1016/j.jhep.2008.02.011. PMCID: PMC2423467 NIHMSID: NIHMS52684 Copyright notice and Disclaimer Fructose Consumption as a Risk Factor for Non-alcoholic Fatty Liver Disease Xiaosen Ouyang, MD,1* Pietro Cirillo, MD,1* Yuri Sautin, PhD,1* Shannon McCall, MD,2‡ James L. Bruchette, ASCP,2‡ Anna Mae Diehl, MD,3‡ Richard J. Johnson, MD,1* and Manal F. Abdelmalek, MD3‡