Does Sugar Caramelize the Heart?
by Kimberly Pryor
When the general population discusses heart health, a lot of attention is paid to the effects of saturated fats on the cardiovascular system and on lipid levels. However, little attention is paid to the heart-harming consequences of consuming sugar. Yet, although saturated fat has taken the blame as the major dietary villain, mounting research suggests that sugar is one of the heart’s worst enemies.
Both sucrose and high-fructose corn syrup are major components of Western diets. Sweetened drinks such as soft drinks are the largest contributor to added sugar intake in the U.S. The use of added sweeteners containing fructose (sucrose and high-fructose corn syrup) has increased by 25 percent over the past thirty years.1
In recent decades, rising intake of sugar-sweetened beverages—including soft drinks, fruitades, fruit drinks, vitamin water drinks, sweetened iced tea and lemonade—has closely paralleled the increase in obesity. It has long been suspected that sugar-sweetened beverages may be responsible for the obesity epidemic; however, only recently have large epidemiological studies established the association between sugar-sweetened beverage consumption and long-term weight gain, type 2 diabetes and cardiovascular disease risk.2
Alarming Research
One of the newest studies about sugar’s effect on heart health, published in the journal Circulation, found that teenagers who consume large amounts of sugary foods and drinks are more likely to have risk factors for heart disease. The study authors examined the sugar-consuming habits of 2,157 teens who participated in the National Health and Nutrition Examination Survey (NHANES) from 1999 to 2004. Among the participants, daily consumption of added sugars averaged 21.4 percent of total energy. The results of the study indicated that the more added sugar teenagers consumed, the more significant was the association with factors known to increase cardiovascular disease risk. For example, the higher the intake of added sugars, the lower the mean high-density lipoprotein (HDL) cholesterol levels. Added sugars also were positively associated with levels of low-density lipoproteins (LDL) and triglycerides.3
A study in adults drew similar conclusions. The study authors looked at 6,113 subjects who were participating in the National Health and Nutrition Examination Survey (NHANES) from 1999 to 2006. Respondents were grouped by intake of added sugars. The study found that the higher the consumption of sugar, the lower the levels of HDL cholesterol and the higher the levels of triglycerides. In fact, among subjects eating more sugar (10 percent or more added sugars) the odds of having low HDL cholesterol levels were 50 percent to more than 300 percent greater compared with the group consuming less than 5 percent added sugars. In the female subjects, higher sugar intake also was associated with higher LDL cholesterol levels.4
A recent report from the Nurses’ Health Study showed that women who consumed diets with a high-glycemic load (increased intake of sweets or highly processed starches and sweets) had an increased coronary heart disease (CHD) risk. Subjects who consumed the highest amounts of high-glycemic foods had a greater than 2-fold risk of coronary heart disease during 10 years of follow-up.5
A diet high in sucrose (greater than 20 percent of energy) also is associated with an elevation of plasma triglyceride concentrations.6-7 This increase is due to both increased hepatic secretion and impaired clearance of very-low-density lipoprotein.
Detrimental effects of sugar consumption also have been found in animals. In mice with impaired mitochondrial metabolism, a high-sucrose/low-fat diet has detrimental effects on the heart, promoting several independent cardiovascular risk factors, including impaired glucose metabolism, fasting hyperinsulinemia, reduced glucose-stimulated insulin secretion, increased serum triglycerides, and elevated cholesterol levels due to increased expression of HMG-CoA reductase. By contrast, a high-saturated fat/low-sugar diet protects mice with impaired mitochondrial metabolism from diet-induced obesity by increasing total energy expenditure and increasing expression of ACAA2, a rate-limiting enzyme of mitochondrial beta-oxidation.8
The increase in dietary consumption of sugar has gone hand in hand with a dramatic rise in the prevalence of insulin resistance, a condition that is linked to poor heart health. Excessive fructose intake, particularly of high fructose corn syrup, has the potential to adversely influence systemic and cellular metabolism via insulin resistance. Excessive consumption of fructose and sucrose also can disrupt glycolysis, the metabolic pathway that converts glucose to pyruvate. The free energy released in this process helps form the high-energy compounds ATP and NADH. Because the heart is both insulin sensitive and glycolysis dependent, it may be especially vulnerable to fructose and sucrose over-consumption.1
Sugar Caramelizes the Heart
One of sugar’s most destructive effects on the heart is its tendency to encourage the formation of AGEs—advanced glycation end products—in the body. AGEs are the final product of a series of complex rearrangements—often called cross-linking—resulting from the reaction of circulating sugars with proteins. AGE formation in the body results from the same process that caramelizes sugar when it’s cooked and the process that turns bread brown during toasting. This process is known as the Maillard reaction. Consumption of excessive amounts of fructose and sucrose are known to stimulate AGE production by reacting with protein molecules, triggering the Maillard reaction.9-11
The cardiovascular system is particularly susceptible to the effects of AGEs because AGEs accumulate on vascular wall proteins, which have a slow turnover rate. One of the first hallmarks of AGE formation is the accumulation of AGEs on collagen, forming intermolecular bonds leading to an increased stiffness of collagen fibers. Although it’s not completely clear how AGE-accumulation on collagen fibers affect the mechanical properties of the arterial wall, the mechanical properties of the arterial wall are major determinants of the left ventricular-arterial function. Therefore, AGE-related alterations of mechanical properties of the arterial wall might have important consequences on cardiovascular performance, especially in diabetics, whose blood sugar disturbances result in higher accumulation of AGEs.12-13 Glycation effects on the arterial wall also promote LDL accumulation as well as reduce the elasticity of vessel walls.14
In fact, scientists have found that AGE-modified LDL is as destructive as oxidized LDL (oxLDL). High cholesterol levels in circulating immune complexes are surrogate markers of modified LDL and are associated with increased carotid intima-media thickness and cardiovascular events in type 1 diabetes. In 479 diabetes patients, individuals who had the highest levels of AGE-modified LDL in their immune complexes had a 6.4-fold increase in the odds of having high carotid intima-media thickness, after adjusting for conventional risk factors. The subjects with the highest levels of oxLDL had a 6.11-fold increase in the odds of having high carotid intima-media thickness.15
In another study of 169 individuals with diabetic nephropathy and 170 individuals with persistent normoalbuminuria who were free of cardiovascular disease (CVD) at study entry, researchers determined baseline AGE levels. The incidence of fatal and nonfatal CVD and of all-cause mortality increased with higher baseline levels of AGEs independently of traditional CVD risk factors.16
Furthermore, in hemodialysis patients, researchers found that the higher the level of tissue AGEs the higher the level of high sensitivity C-reactive protein, a marker of cardiovascular disease that predicts future cardiovascular events in patients undergoing hemodialysis.17 This led the study authors to conclude, “Tissue AGE and hsCRP levels may be correlated with each other, which could in concert contribute to the progression of atherosclerosis in these subjects.”
AGE-Blocking, Blood-Sugar Balancing Approach
Proper dietary choices are, of course, important in stopping the damaging effects of AGEs on the heart. However, AGEs are widespread in the diet. They can be produced even when meat is cooked at high temperatures. Even infant formula has high levels of AGEs, indicating that people are exposed to AGEs from a very early age.18 AGEs also are produced in the body as a result of imbalanced metabolic processes and can’t be completely avoided.
Therefore, nutritional support with N-acetyl cysteine (NAC), lipoic acid, carnosine, guava, Yerba maté and benfotiamine (all found in AGEBlock®) can help offset the onslaught of heart-harming AGEs that we encounter daily.
N-acetyl cysteine (NAC) is one of the most potent natural AGE-inhibitors. NAC stops AGEs from initiating changes to LDL cholesterol that make this “bad” form of cholesterol even more destructive.19 By increasing glutathione, NAC also reduces lipid peroxidation that occurs in neuronal cell lines after AGE exposure.20 Studies have found that lipoic acid is also very active in inhibiting AGEs. Rats fed lipoic acid and a high-fructose diet showed significant reductions in AGE formation,21 while carnosine has been reported to retard and in some cases even reverse the glycation process.22 Carnosine and its primary functional amino acid l-histidine can inhibit LDL glycation and oxidation.23
A lesser known AGE-blocking agent is guava (Psidium guajava extract), which has a significant and inhibitory dose-dependent effect on LDL glycation.24 Yerba maté (Ilex paraguariensis extract) is emerging as another powerful AGE-blocking substance. In a recent study, Yerba maté significantly prevented AGE formation.25
Benfotiamine, a form of vitamin B1, also is a well-researched AGE blocker that significantly reduces AGE levels after the consumption of a high-AGE meal.26
Combining the above substances with quercetin, bitter melon, goat’s rue, cinnamon and vanadyl sulfate (all found in GluControl™) can increase the effectiveness of an AGE-blocking regimen. Each of these substances has been found to support healthy blood sugar levels.27-31
Enhancing Heart Health
Taurine, L-arginine, L-carnitine, Hawthorn (Crataegus oxyacantha), forskolin and Salvia (Salvia miltiorrhiza), all found in CardioCare, can be used to strengthen the heart and prepare it for the inevitable assault of AGEs. Each of the ingredients above are shown to support heart health in various ways, including protecting against ischemia-reperfusion injury, protecting cardiomyocytes (heart cells) against damage, supporting healthy blood pressure, and inhibiting platelet aggregation.32-35
Furthermore, Salvia has been found in vitro to have potent AGE-inhibiting effects.36 L-Carnitine also has antiglycation effects and enhances glucose disposal in rodents exposed to a high-fructose diet.37
Conclusion
Sugar and refined carbohydrates increase the production of AGEs in the body, creating an effect similar to caramelization. Because the heart is particularly vulnerable to the effect of AGEs, supplementation with key botanicals, amino acids and other nutrients can provide much needed support.
References
1. Mellor KM, Ritchie RH, Davidoff AJ, Delbridge LM. Elevated dietary sugar and the heart: experimental models and myocardial remodeling. Can J Physiol Pharmacol. 2010 May;88(5):525-40.
2. Hu FB, Malik VS. Sugar-sweetened beverages and risk of obesity and type 2 diabetes: epidemiologic evidence. Physiol Behav. 2010 Apr 26;100(1):47-54.
3. Welsh JA, Sharma A, Cunningham SA, Vos MB. Consumption of Added Sugars and Indicators of Cardiovascular Disease Risk Among US Adolescents. Circulation. 2011 Jan 25;123(3):249-57.
4. Welsh JA, Sharma A, Abramson JL, Vaccarino V, Gillespie C, Vos MB. Caloric sweetener consumption and dyslipidemia among US adults. JAMA. 2010 Apr 21;303(15):1490-7.
5. Liu S, Willett WC, Stampfer MJ, et al. A prospective study of dietary glycemic load, carbohydrate intake, and risk of coronary heart disease in US women. Am J Clin Nutr. 2000;71:1455-1461.
6. Parks EJ, Hellerstein MK. Carbohydrate-induced hypertriacylglycerolemia: historical perspective and review of biological mechanisms. Am J Clin Nutr. 2000;71:412-433.
7. Frayn KN, Kingman SM. Dietary sugars and lipid metabolism in humans. Am J Clin Nutr. 1995;62(suppl):250S-261S.
8. Kuhlow D, Zarse K, Voigt A, Schulz TJ, Petzke KJ, Schomburg L, Pfeiffer AF, Ristow M. Opposing effects of dietary sugar and saturated fat on cardiovascular risk factors and glucose metabolism in mitochondrially impaired mice. Eur J Nutr. 2010 Oct;49(7):417-27.
9. Gaby AR. Adverse Effects of Dietary Fructose. Alternative Medicine Review. 2005;10(4):294-306.
10. Stanhope KL, Havel PJ. Fructose consumption: recent results and their potential implications. Ann N Y Acad Sci. 2010 Mar;1190:15-24.
11. Carvalho CR, Bueno AA, Mattos AM, Biz C, de Oliveira C, Pisani LP, Ribeiro EB, do Nascimento CM, Oyama LM. Fructose alters adiponectin, haptoglobin and angiotensinogen gene expression in 3T3-L1 adipocytes. Nutr Res. 2010 Sep;30(9):644-9.
12. Huijberts M, Wolffenbuttel B, Struijker Boudier H, Crijns F, Nieuwenhuijzen Kruseman A, Poitevin P, Levy B. Aminoguanidine Treatment Increases Elasticity and Decreases Fluid Filtration of Large Arteries from Diabetic Rats. J Clin Invest. September 1993;92:1407-1411.
13. Airaksinen KE, Salmela PI, Linnaluoto MK, Ikäheimo MJ, Ahola K, Ryhänen LJ. Diminished arterial elasticity in diabetes: association with fluorescent advanced glycosylation end products in collagen. Cardiovasc Res. 1993 Jun;27(6):942-5.
14. Pamplona R, Bellmunt MJ, Portero M, Prat J. Mechanisms of glycation in atherogenesis. Med Hypotheses. 1993 Mar;40(3):174-81.
15. Lopes-Virella MF, Hunt KJ, Baker NL, Lachin J, Nathan DM, Virella G. Levels of Oxidized LDL and Advanced Glycation End Products-Modified LDL in Circulating Immune Complexes Are Strongly Associated With Increased Levels of Carotid Intima-Media Thickness and Its Progression in Type 1 Diabetes. 2011 Feb;60(2):582-589.
16. Nin JW, Jorsal A, Ferreira I, Schalkwijk CG, Prins MH, Parving HH, Tarnow L, Rossing P, Stehouwer CD. Higher Plasma Levels of Advanced Glycation End Products Are Associated With Incident Cardiovascular Disease and All-Cause Mortality in Type 1 Diabetes: A 12-year follow-up study. Diabetes Care. 2011 Feb;34(2):442-447.
17. Nagano M, Fukami K, Yamagishi SI, Sakai K, Kaida Y, Matsumoto T, Hazama T, Tanaka M, Ueda S, Okuda S. Tissue level of advanced glycation end products (AGEs) is an independent determinant of high sensitive C-reactive protein levels in hemodialysis patients. Nephrology (Carlton). 2010 Nov 3. Published Online Ahead of Print.
18. Elliott RB. Diabetes—a man made disease. Med Hypotheses. 2006;67(2):388-91.
19. Cai W, He JC, Zhu L, Peppa M, Lu C, Uribarri J, Vlassara H. High levels of dietary advanced glycation end products transform low-density lipoprotein into a potent redox-sensitive mitogen-activated protein kinase stimulant in diabetic patients. Circulation. 2004 Jul 20;110(3):285-91.
20. Gasic-Milenkovic J, Loske C, Münch G. Advanced glycation endproducts cause lipid peroxidation in the human neuronal cell line SH-SY5Y. J Alzheimers Dis. 2003 Feb;5(1):25-30.
21. Thirunavukkarasu V, Anitha Nandhini AT, Anuradha CV. Lipoic acid improves glucose utilisation and prevents protein glycation and AGE formation. Pharmazie. 2005 Oct;60(10):772-5.
22. Szwergold BS. Carnosine and anserine act as effective transglycating agents in decomposition of aldose-derived Schiff bases. Biochem Biophys Res Commun. 2005 Oct 14;336(1):36-41.
23. Rashid I, van Reyk DM, Davies MJ. Carnosine and its constituents inhibit glycation of low-density lipoproteins that promotes foam cell formation in vitro. FEBS Lett. 2007 Mar 6;581(5):1067-70.
24. Hsieh CL, Yang MH, Chyau CC, Chiu CH, Wang HE, Lin YC, Chiu WT, Peng RY. Kinetic analysis on the sensitivity of glucose- or glyoxal-induced LDL glycation to the inhibitory effect of Psidium guajava extract in a physiomimic system. Biosystems. 2007 Mar;88(1-2):92-100.
25. Lunceford N, Gugliucci A. Ilex paraguariensis extracts inhibit AGE formation more efficiently than green tea. Fitoterapia. 2005 Jul;76(5):419-27.
26. Stirban A, Negrean M, Stratmann B, Gawlowski T, Horstmann T, Götting C, Kleesiek K, Mueller-Roesel M, Koschinsky T, Uribarri J, Vlassara H, Tschoepe D. Benfotiamine prevents macro- and microvascular endothelial dysfunction and oxidative stress following a meal rich in advanced glycation end products in individuals with type 2 diabetes. Diabetes Care. 2006 Sep;29(9):2064-71.
27. Mang B, Wolters M, Schmitt B, et al. Effects of a cinnamon extract on plasma glucose, HbA, and serum lipids in diabetes mellitus type 2. Eur J Clin Invest. 2006 May;36(5):340-4.
28. Ahmad N, Hassan MR, Halder H, et al. Effect of Momordica charantia (Karolla) extracts on fasting and postprandial serum glucose levels in NIDDM patients. Bangladesh Med Res Counc Bull. 1999 Apr;25(1):11-3.
29. Broadhurst CL, Domenico P. Clinical studies on chromium picolinate supplementation in diabetes mellitus—a review. Diabetes Technol Ther. 2006 Dec;8(6):677-87.
30. Goldfine AB, Patti ME, Zuberi L, et al. Metabolic effects of vanadyl sulfate in humans with non–insulindependent diabetes mellitus: In vivo and in vitro studies. Metabolism. 2000;49(3):400-410.
31. Khan A, Safdar M, Ali Khan MM, et al. Cinnamon improves glucose and lipids of people with type 2 diabetes. Diabetes Care. 2003 Dec;26(12):3215-8.
32. Ghosh J, Das J, Manna P, Sil PC. Taurine prevents arsenic-induced cardiac oxidative stress and apoptotic damage: role of NF-kappa B, p38 and JNK MAPK pathway. Toxicol Appl Pharmacol. 2009 Oct 1;240(1):73-87.
33. Ling S, Luo R, Dai A, Guo Z, Guo R, Komesaroff PA. A pharmaceutical preparation of Salvia miltiorrhiza protects cardiac myocytes from tumor necrosis factor-induced apoptosis and reduces angiotensin II-stimulated collagen synthesis in fibroblasts. Phytomedicine. 2009 Jan;16(1):56-64.
34. Kendler BS. Carnitine: an overview of its role in preventive medicine. Prev Med. 1986 Jul;15(4):373-90.
35. Holubarsch CJ, Colucci WS, Meinertz T, Gaus W, Tendera M. The efficacy and safety of Crataegus extract WS(R) 1442 in patients with heart failure: The SPICE trial. Eur J Heart Fail. 2008 Nov 17. Published Online Ahead of Print.
36. Ma HY, Gao HY, Sun L, Huang J, Xu XM, Wu LJ. Constituents with a-glucosidase and advanced glycation end-product formation inhibitory activities from Salvia miltiorrhiza Bge. J Nat Med. 2011 Jan;65(1):37-42.
37. Rajasekar P, Anuradha CV. L-Carnitine inhibits protein glycation in vitro and in vivo: evidence for a role in diabetic management. Acta Diabetol. 2007 Jun;44(2):83-90.
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