14 replies to this topic

[Blue]

Interesting review:
http://74.125.155.13...m....com/&hl=en

Fascinating that pre- and probiotics (lactobacteria is mentioned) may reduce these substances from food.

[Mikiomiles23]

Interesting review:
http://74.125.155.13...m....com/&hl=en

Fascinating that pre- and probiotics (lactobacteria is mentioned) may reduce these substances from food.

Wow, that's really interesting, Blue. Do you mean, by taking excess pre/probiotics, or the ones that occur naturally?

[health_nutty]

Interesting review:
http://74.125.155.13...m....com/&hl=en

Fascinating that pre- and probiotics (lactobacteria is mentioned) may reduce these substances from food.

Indeed, very nice find!

[JLL]

Seems like a very biased article to me... they correctly identify lipoxidation as a source for ALEs, and yet state that a high intake of saturated fats and low intake of polyunsaturated fats is the problem, even though it's precisely PUFAs that undergo lipid peroxidation to form ALEs.

The explanation for the differences is that lipid peroxidation increases exponentially as a function of the number of double bonds (link), i.e. the degree of unsaturation. Arachidonic acid is a 20-carbon chain PUFA with four double bonds and linoleic acid is an 18-carbon chain PUFA with two double bonds. Oleic acid, like all MUFAs, has one double bond. Note that this equation makes the omega-3 fatty acids DHA and EPA (with their 6 and 5 double bonds, respectively) the worst offenders.

Their analysis of the higher AGE levels in vegetarians is also wrong. They suggest either fructose or dairy consumption is the culprit, but this can't be correct, because even though vegans have higher intake of fructose (and fructose is indeed prone to cause AGEs), they still have lower levels of AGEs than lacto-ovo-vegetarians and semi-vegans. As I recall, their consumption of dairy was not higher than that of omnivores, who had lower levels of AGEs.

I guess it's possible that dairy products, which are somewhat high in AGEs, really are a big problem, and that the taurine and creatine in meat protect from glycation in omnivores but not in lacto-ovo-vegetarians, but I think that theory would require more evidence behind it. Rather, the conclusion that makes more sense is that endogenous AGEs are more important than exogenous AGEs. Their suggestion that coffee is somehow a big contributor to dietary AGEs is ridiculous -- one cup of coffee has 4 kU of AGEs, while an avocado has 473 kU.

There are two ways to interpret their theory: the first is that it's AGEs/ALEs created within the body that are the problem, in which case their recommendation to cut back on saturated fat and increase PUFA intake can't make sense; and the second is that it's AGEs/ALEs in food that is the problem, in which case their recommendation to increase vegetables and PUFAs and to cut back on milk (12 kU AGEs / serving) and coffee does not make sense either.

[John Schloendorn]

The paper suggests that

Chronic diseases are repeatedly associated to accumulation in the body of glycated and lipoxidated proteins

but then goes on about non-accumulating, dietary AGEs and ALEs. What is the evidence that these transient forms do indeed contribute to chronic diseases?

Edited by John Schloendorn, 13 October 2009 - 06:39 PM.

[Blue]

Regarding coffee, it do looks like something bad happens to it when roasted:
"In this study, we investigated the immunomodulatory activity of coffee and Maillard reaction products on macrophages in vitro. Stimulation of macrophages with coffee, but not with raw coffee extract in PBS, led to a 13-fold increased nuclear NF-B translocation. A Maillard reaction mixture (25 mM D-ribose/L-lysine, 30 min at 120°C) increased NF-B translocation 18-fold (in PBS) or six-fold (in medium). MRPs also induced a two-fold increased NF-B translocation in untransfected human embryonic kidney (HEK) cells as well as in HEK cells stably transfected with the receptor for advanced glycation endproducts (RAGE), indicating that the effect was not RAGE mediated. On the other hand, catalase totally abolished coffee- and MRP-induced NF-B translocation. Consequently, up to 366 M hydrogen peroxide was measured in the coffee preparation and Maillard mixtures used for cell stimulation. Stimulation of macrophages with MRPs did not lead to significantly increased IL-6 or NO release. Thus, it can be concluded that coffee and MRPs induce NF-B translocation in macrophages via the generation of hydrogen peroxide."
http://www3.intersci...209241/abstract

[niner]

The paper suggests that

Chronic diseases are repeatedly associated to accumulation in the body of glycated and lipoxidated proteins

but then goes on about non-accumulating, dietary AGEs and ALEs. What is the evidence that these transient forms do indeed contribute to chronic diseases?

Here is some evidence in mice:

Am J Pathol. 2007 Jun;170(6):1893-902. Free Full Text
Reduced oxidant stress and extended lifespan in mice exposed to a low glycotoxin diet: association with increased AGER1 expression.
Cai W, He JC, Zhu L, Chen X, Wallenstein S, Striker GE, Vlassara H.

Mount Sinai School of Medicine, Box 1640, One Gustave Levy Place, New York, NY 10029, USA.

Aging is accompanied by increased oxidative stress (OS) and accumulation of advanced glycation end products (AGEs). AGE formation in food is temperature-regulated, and ingestion of nutrients prepared with excess heat promotes AGE formation, OS, and cardiovascular disease in mice. We hypothesized that sustained exposure to the high levels of pro-oxidant AGEs in normal diets (Reg(AGE)) contributes to aging via an increased AGE load, which causes AGER1 dysregulation and depletion of anti-oxidant capacity, and that an isocaloric, but AGE-restricted (by 50%) diet (Low(AGE)), would decrease these abnormalities. C57BL6 male mice with a life-long exposure to a Low(AGE) diet had higher than baseline levels of tissue AGER1 and glutathione/oxidized glutathione and reduced plasma 8-isoprostanes and tissue RAGE and p66(shc) levels compared with mice pair-fed the regular (Reg(AGE)) diet. This was associated with a reduction in systemic AGE accumulation and amelioration of insulin resistance, albuminuria, and glomerulosclerosis. Moreover, lifespan was extended in Low(AGE) mice, compared with Reg(AGE) mice. Thus, OS-dependent metabolic and end organ dysfunction of aging may result from life-long exposure to high levels of glycoxidants that exceed AGER1 and anti-oxidant reserve capacity. A reduced AGE diet preserved these innate defenses, resulting in decreased tissue damage and a longer lifespan in mice.

PMID: 17525257

And here is some in humans:

J Clin Endocrinol Metab. 2009 Oct 9. [Epub ahead of print]
Protection against Loss of Innate Defenses in Adulthood by Low Advanced Glycation End Products (AGE) Intake: Role of the Antiinflammatory AGE Receptor-1.
Vlassara H, Cai W, Goodman S, Pyzik R, Yong A, Chen X, Zhu L, Neade T, Beeri M, Silverman JM, Ferrucci L, Tansman L, Striker GE, Uribarri J.

Division of Experimental Diabetes and Aging (H.V., W.C., S.G., R.P., A.Y., X.C., L.Z., G.E.S.), Brookdale Department of Adult Development and Geriatrics, Department of Medicine (T.N., G.E.S., J.U.), Division of Nephrology, and Departments of Psychiatry (J.M.S.) and Community and Preventive Medicine (L.T.), Mount Sinai School of Medicine, New York, New York 10029; and National Institute on Aging (L.F.), National Institutes of Health, Bethesda, Maryland 20892.

Context: Increased oxidant stress and inflammation (OS/infl) are linked to both aging-related diseases and advanced glycation end products (AGEs). Whereas AGE receptor-1 (AGER1) reduces OS/infl in animals, this has not been assessed in normal humans. Objective: The objectives of the study were to determine whether AGER1 correlates with AGEs and OS/infl and a reduction of dietary AGEs (dAGEs) lowers OS/infl in healthy adults and chronic kidney disease (CKD-3) patients. Design: This study was cross-sectional with 2-yr follow-up studies of healthy adults and CKD-3 patients, a subset of which received a reduced AGE or regular diet. Setting: The study was conducted at general community and renal clinics. Participants: Participants included 325 healthy adults (18-45 and >60 yr old) and 66 CKD-3 patients. Intervention: An isocaloric low-AGE (30-50% reduction) or regular diet was given to 40 healthy subjects for 4 months and to nine CKD-3 patients for 4 wk. Main Outcome: Relationships between age, dAGEs, serum AGEs, peripheral mononuclear cell AGE-receptors, and OS/Infl before and after reduction of dAGE intake were measured. Results: AGEs, oxidant stress, receptor for AGE, and TNFalpha were reduced in normal and CKD-3 patients after the low-AGE diet, independently of age. AGER1 levels in CKD-3 patients on the low-AGE diet resembled 18- to 45-yr-old normal subjects. Dietary, serum, and urine AGEs correlated positively with peripheral mononuclear cell AGER1 levels in healthy participants. AGER1 was suppressed in CKD-3 subjects, whereas receptor for AGE and TNFalpha were increased. Conclusions: Reduction of AGEs in normal diets may lower oxidant stress/inflammation and restore levels of AGER1, an antioxidant, in healthy and aging subjects and CKD-3 patients. AGE intake has implications for health outcomes and costs and warrants further testing.

PMID: 19820033

[Blue]

Regarding the high ageps in vegetarians, I have seen these theories:
1. High fructose
2. High milk products
3. High polyunsaturated fats
4. Low taurine
5. Low carnosine/beta-alanine

Low creatine may possible decrease ageps in vegetarians:
http://sciencelinks....402A0838274.php

JLL has a nice blogpost about this (linked above but here again since it is interesting):
http://inhumanexperi...-comparing.html

Edited by Blue, 13 October 2009 - 08:06 PM.

[Blue]

The always beloved carnitine is another possiblity:
http://www.springerl...4r272087260996/

[Sillewater]

As far as I read in the abstract the creatine will form an pentosidine structure. So would supplementing with creatine prevent the endogenous damage of our protein structures or does it contribute to it? Would it be like how supplementing with free lysine, arginine, carnosine, taurine, carnitine protects from glycation damage?

Edited by Sillewater, 16 December 2009 - 10:45 AM.

[Blue]

As far as I read in the abstract the creatine will form an pentosidine structure. So would supplementing with creatine prevent the endogenous damage of our protein structures or does it contribute to it? Would it be like how supplementing with free lysine, arginine, carnosine, taurine, carnitine protects from glycation damage?

Title:
Creatine Plays a Direct Role as a Protein Modifier in the Formation of a Novel Advanced Glycation End Product.

Abstract; Pentosidine, a cross-link structure between lysine and arginine residues, is one of the major advanced glycation end products (AGE). It is formed by the reaction of ribose with lysine and arginine. The pentosidine concentration produced by in vitro incubation of plasma obtained from uremic patients was reported to be higher than in normal plasma, indicating that uremic plasma contains an enhancer(s) for pentosidine formation [Miyata, T., Ueda, Y., Yamada, Y., Izuhara, Y., Wada, T., Jadoul, M., Saito, A., Kurokawa, K., and Strihou, C.Y. (1998) J. Am. Soc. Nephrol. 9, 2349-2356]. Since our preliminary study using a monoclonal anti-pentosidine antibody identified creatine as the most effective enhancer, the purpose of the present study was to clarify the mechanism by which creatine contributes to pentosidine formation. Lysine was incubated with ribose in the presence of creatine and analyzed by reverse phase high performance liquid chromatography. A novel fluorescent peak (.LAMBDA.ex/em = 335/385 nm) was detected at 8 min, under conditions at which the authentic pentosidine (lysine was incubated with ribose in the presence of arginine under identical conditions) eluted at 12 min. Structural analyses of this compound revealed a pentosidine-like structure in which the arginine residue was replaced by creatine. This novel AGE-structure, named here creatine-derived pentosidine (C-pentosidine), was detected in the plasma of patients on hemodialysis. These results indicate that creatine increases the formation of C-pentosidine but not authentic pentosidine. This study indicates that creatine plays a direct role as a protein modifier in C-pentosidine formation, although the clinical significance of C-pentosidine is still unknown. (author abst.)"
http://sciencelinks....402A0838274.php

Edited by Blue, 16 December 2009 - 10:58 AM.

[Blue]

Seems to have been little follow-up of the above study. Not sure how to view c-pentosidine. Anyone has a study?

[Sillewater]

Ah I see, thanks for highlighting those points. Totally misunderstood the abstract.

Critical evaluation of toxic versus beneficial effects of methylglyoxal
Advanced glycation end-products (AGEs): involvement in aging and in neurodegenerative diseases

Does anyone have access to these papers?

Edited by Sillewater, 16 December 2009 - 09:55 PM.

[kismet]

Blue, I'm most definitely interested. This creatine thingy is getting scarry. 

#2 uploaded in members section (fair use and all that...)

[VidX]

So I take that I better refrain from ordering that creatine powder to help in my workouts.?