Cooking Toxin (AGEs) Research
Research suggests that most AGEs come from the diet and they may do harm like accelerate aging.
Does Accumulation of Advanced Glycation End Products Contribute to the Aging Phenotype?
Received December 12, 2009.
(a review of the scientific literature)
Richard D. Semba1, Emily J. Nicklett2 and Luigi Ferrucci3
http://biomedgerontology.oxfordjournals.org/content/65A/9/963.full
> "Current evidence from many different disciplines lends strong support to the idea that AGEs contribute to the multisystem decline that occurs with aging. AGEs contribute to inflammation and tissue damage through AGE-RAGE binding. AGEs cross-link collagen and other proteins and thus increase the stiffness of tissues such as the major arteries, heart, bone, and muscle. Histopathological studies show that AGE and RAGE are associated with the lesions of Alzheimer’s disease; age-related macular degeneration; atherosclerosis; glomerulosclerosis; and interstitial fibrosis in the kidney, osteoporosis, and sarcopenia. The harmful effects of AGEs on various organs and tissues have been demonstrated in animal models."
> "The contribution of dietary AGEs to the total pool of AGEs in the body is much greater than the contribution from AGEs that are endogenously generated by abnormal glucose metabolism or lipid oxidation (99 Henle T. AGEs in foods: do they play a role in uremia? Kidney Int 2003;63(suppl 84):S145-S147.
http://www.nature.com/ki/journal/v63/n84s/full/4493792a.html). It has been estimated that humans usually consume 25-75 mg of AGEs per day, mostly as CML and pyrraline (99). Controlled feeding studies in animals show that about 30% of dietary CML is absorbed into the circulation (100). Whether dietary AGEs have an adverse impact upon human health has not been conclusively demonstrated (101-103). There have been a small number of short-term dietary studies which show that AGEs in foods are absorbed during digestion and that a portion of the ingested AGEs are excreted in the urine (104-106). Three dietary intervention studies conducted in adults with diabetes suggest that single meals or single oral challenges with high AGE content lead to large postprandial increases in serum AGEs (10,107). In adults with type 2 diabetes, a single AGE-rich meal resulted in impaired flow-mediated dilatation, elevated adhesion molecules, and higher levels of a marker for oxidative stress compared with the meal that was low in AGEs (107). A single oral challenge with a 10-fold concentrate of a cola beverage resulted in impaired flow-mediated dilatation and an increase in serum AGEs at 90 minutes post-challenge (108). The results of these last three intervention studies have not been independently corroborated. A recent randomized, crossover, diet-controlled intervention trial, conducted in 62 healthy student volunteers, compared the effects of a steamed diet (low in AGEs) with a high heat-treated diet (high in AGEs) (109). After 1 month, consumption of the high heat-treated diet was associated with higher plasma CML concentrations, reduced insulin sensitivity, and increased plasma cholesterol and triglycerides compared with the steamed diet (109). The interindividual variability in the absorption of AGEs in humans has not been well studied. This variability could potentially contribute to differences in plasma CML levels and to variability in the aging process. In addition, the amount of absorption of different AGEs found in foods was not been well characterized."
Henle T. AGEs in foods: do they play a role in uremia? Kidney Int 2003;63(suppl 84):S145-S147.
http://www.nature.com/ki/journal/v63/n84s/full/4493792a.html
"the major part of AGEs measured in urine is of dietary origin. Similar results were observed for PD-effluates. This gives the preliminary indication that dietary AGEs might significantly contribute to the total AGE load of the human body. The kidney, as well as the peritoneal membrane, has to deal with a "continuous" exposure to dietary AGEs. Therefore, biologic effects of these exogenously formed compounds have to be considered, in addition to AGEs formed endogenously."
Šebeková, Katarína et al. Plasma levels of advanced glycation end products in healthy, long-term vegetarians and subjects on a western mixed diet, http://www.springerlink.com/content/6mhb24hyajh4qkk1/fulltext.pdf
Healthy vegetarians have higher levels of AGEs than Western diet omnivores, likely due to consumption of more AGEs in foods, according to the authors.
Glycation in food and metabolic transit of dietary AGEs
http://www.biochemsoctrans.org/bst/031/1383/0311383.pdf
> "pyrraline obviously is not metabolized within the body" (so high pyrraline can't be blamed on endogenous AGEs; it must come from the diet)
> "Our results indicate that the healthy kidney is capable of clearing dietary AGEs efficiently from the circulation. Nevertheless, further studies are necessary in order to clarify whether accumulating dietary AGEs might contribute significantly to the AGE load of the human body, especially in uraemia, and therefore may have to be taken into account for certain physiological consequences. Above all, however, it has to be realized that the term ‘AGE’ comprises a large number of individual amino acid derivatives, of which only a minority have been identified and quantified either in foods or [i]in vivo[/i]."
> "The results of this work prove, for the first time, that urinary excretion of pyrraline is strongly
dependent on its dietary intake. Thus the influence of nutrition should be taken into consideration in studies directed to the physiological role of glycation compounds."
Advanced Glycation and Lipoxidation End Products–Amplifiers of Inflammation: The Role of Food
Stig Bengmark, MD, PhD, FRACS (hon), FRCPS (hon)
[A review of 800 full papers and thousands of abstracts]
http://www.ncbi.nlm.nih.gov/pubmed/17712153
http://pen.sagepub.com/content/31/5/430.full
"Results: RAGE, a member of the immunoglobulin superfamily of cell surface molecules and receptor for advanced glycation end products, known since 1992, functions as a master switch, induces sustained activation of nuclear factor kappaB (NFkappaB), suppresses a series of endogenous autoregulatory functions, and converts long-lasting proinflammatory signals into sustained cellular dysfunction and disease. Its activation is associated with high levels of dysfunctioning proteins in body fluids and tissues, and is strongly associated with a series of diseases from allergy and Alzheimers to rheumatoid arthritis and urogenital disorders. Heat treatment, irradiation, and ionization of foods increase the content of dysfunctioning molecules.
It has also been observed that accumulation of AGEs/ALEs in the skin reflects the AGE/ALE deposition in the rest of the body to such a degree that skin autofluorescence has been suggested as a measure of cumulative metabolic stress and AGEs in the body.118 Skin autofluorescence is suggested to be so exact that it is able to predict progression of retinopathy and nephropathy in DM, as well as mortality in hemodialysis patients.118 [Meerwaldt R, Hartog JW, Graaff R, et al. Skin autofluorescence, a measure of cumulative metabolic stress and advanced glycation end products, predicts mortality in hemodialysis patients. J Am Soc Nephrol. 2005;16:3687–3693: "Skin AF is a strong and independent predictor of mortality in ESRD. This supports a role for AGE as a contributor to mortality and CVD and warrants interventions specifically aimed at AGE accumulation.]"
Does Accumulation of Advanced Glycation End Products Contribute to the Aging Phenotype?
Received December 12, 2009.
(a review of the scientific literature)
Richard D. Semba1, Emily J. Nicklett2 and Luigi Ferrucci3
http://biomedgerontology.oxfordjournals.org/content/65A/9/963.full
> "Current evidence from many different disciplines lends strong support to the idea that AGEs contribute to the multisystem decline that occurs with aging. AGEs contribute to inflammation and tissue damage through AGE-RAGE binding. AGEs cross-link collagen and other proteins and thus increase the stiffness of tissues such as the major arteries, heart, bone, and muscle. Histopathological studies show that AGE and RAGE are associated with the lesions of Alzheimer’s disease; age-related macular degeneration; atherosclerosis; glomerulosclerosis; and interstitial fibrosis in the kidney, osteoporosis, and sarcopenia. The harmful effects of AGEs on various organs and tissues have been demonstrated in animal models."
> "The contribution of dietary AGEs to the total pool of AGEs in the body is much greater than the contribution from AGEs that are endogenously generated by abnormal glucose metabolism or lipid oxidation (99 Henle T. AGEs in foods: do they play a role in uremia? Kidney Int 2003;63(suppl 84):S145-S147.
http://www.nature.com/ki/journal/v63/n84s/full/4493792a.html). It has been estimated that humans usually consume 25-75 mg of AGEs per day, mostly as CML and pyrraline (99). Controlled feeding studies in animals show that about 30% of dietary CML is absorbed into the circulation (100). Whether dietary AGEs have an adverse impact upon human health has not been conclusively demonstrated (101-103). There have been a small number of short-term dietary studies which show that AGEs in foods are absorbed during digestion and that a portion of the ingested AGEs are excreted in the urine (104-106). Three dietary intervention studies conducted in adults with diabetes suggest that single meals or single oral challenges with high AGE content lead to large postprandial increases in serum AGEs (10,107). In adults with type 2 diabetes, a single AGE-rich meal resulted in impaired flow-mediated dilatation, elevated adhesion molecules, and higher levels of a marker for oxidative stress compared with the meal that was low in AGEs (107). A single oral challenge with a 10-fold concentrate of a cola beverage resulted in impaired flow-mediated dilatation and an increase in serum AGEs at 90 minutes post-challenge (108). The results of these last three intervention studies have not been independently corroborated. A recent randomized, crossover, diet-controlled intervention trial, conducted in 62 healthy student volunteers, compared the effects of a steamed diet (low in AGEs) with a high heat-treated diet (high in AGEs) (109). After 1 month, consumption of the high heat-treated diet was associated with higher plasma CML concentrations, reduced insulin sensitivity, and increased plasma cholesterol and triglycerides compared with the steamed diet (109). The interindividual variability in the absorption of AGEs in humans has not been well studied. This variability could potentially contribute to differences in plasma CML levels and to variability in the aging process. In addition, the amount of absorption of different AGEs found in foods was not been well characterized."
Henle T. AGEs in foods: do they play a role in uremia? Kidney Int 2003;63(suppl 84):S145-S147.
http://www.nature.com/ki/journal/v63/n84s/full/4493792a.html
"the major part of AGEs measured in urine is of dietary origin. Similar results were observed for PD-effluates. This gives the preliminary indication that dietary AGEs might significantly contribute to the total AGE load of the human body. The kidney, as well as the peritoneal membrane, has to deal with a "continuous" exposure to dietary AGEs. Therefore, biologic effects of these exogenously formed compounds have to be considered, in addition to AGEs formed endogenously."
Šebeková, Katarína et al. Plasma levels of advanced glycation end products in healthy, long-term vegetarians and subjects on a western mixed diet, http://www.springerlink.com/content/6mhb24hyajh4qkk1/fulltext.pdf
Healthy vegetarians have higher levels of AGEs than Western diet omnivores, likely due to consumption of more AGEs in foods, according to the authors.
Glycation in food and metabolic transit of dietary AGEs
http://www.biochemsoctrans.org/bst/031/1383/0311383.pdf
> "pyrraline obviously is not metabolized within the body" (so high pyrraline can't be blamed on endogenous AGEs; it must come from the diet)
> "Our results indicate that the healthy kidney is capable of clearing dietary AGEs efficiently from the circulation. Nevertheless, further studies are necessary in order to clarify whether accumulating dietary AGEs might contribute significantly to the AGE load of the human body, especially in uraemia, and therefore may have to be taken into account for certain physiological consequences. Above all, however, it has to be realized that the term ‘AGE’ comprises a large number of individual amino acid derivatives, of which only a minority have been identified and quantified either in foods or [i]in vivo[/i]."
> "The results of this work prove, for the first time, that urinary excretion of pyrraline is strongly
dependent on its dietary intake. Thus the influence of nutrition should be taken into consideration in studies directed to the physiological role of glycation compounds."
Advanced Glycation and Lipoxidation End Products–Amplifiers of Inflammation: The Role of Food
Stig Bengmark, MD, PhD, FRACS (hon), FRCPS (hon)
[A review of 800 full papers and thousands of abstracts]
http://www.ncbi.nlm.nih.gov/pubmed/17712153
http://pen.sagepub.com/content/31/5/430.full
"Results: RAGE, a member of the immunoglobulin superfamily of cell surface molecules and receptor for advanced glycation end products, known since 1992, functions as a master switch, induces sustained activation of nuclear factor kappaB (NFkappaB), suppresses a series of endogenous autoregulatory functions, and converts long-lasting proinflammatory signals into sustained cellular dysfunction and disease. Its activation is associated with high levels of dysfunctioning proteins in body fluids and tissues, and is strongly associated with a series of diseases from allergy and Alzheimers to rheumatoid arthritis and urogenital disorders. Heat treatment, irradiation, and ionization of foods increase the content of dysfunctioning molecules.
It has also been observed that accumulation of AGEs/ALEs in the skin reflects the AGE/ALE deposition in the rest of the body to such a degree that skin autofluorescence has been suggested as a measure of cumulative metabolic stress and AGEs in the body.118 Skin autofluorescence is suggested to be so exact that it is able to predict progression of retinopathy and nephropathy in DM, as well as mortality in hemodialysis patients.118 [Meerwaldt R, Hartog JW, Graaff R, et al. Skin autofluorescence, a measure of cumulative metabolic stress and advanced glycation end products, predicts mortality in hemodialysis patients. J Am Soc Nephrol. 2005;16:3687–3693: "Skin AF is a strong and independent predictor of mortality in ESRD. This supports a role for AGE as a contributor to mortality and CVD and warrants interventions specifically aimed at AGE accumulation.]"