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Life Extension Magazine

LE Magazine May 2003

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Eating Food Cooked At High
Temperature Accelerates Aging

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Reversing glycation

In the August 2001 issue of this magazine, an article reported on a compound called ALT-711 that has been shown to partially reverse glycation. Regrettably, the company (Alteon, Inc.) trying to get ALT-711 through the FDA's approval process is woefully under funded, and clinical studies have progressed at a snail's pace.

On January 21, 2003, some encouraging results were announced from a preliminary analysis of a Phase II clinical trial evaluating the activity of ALT-711 in treating diastolic heart failure. The significance of these results is that diastolic heart failure (DHF) is one of the most common types of heart failure in the elderly. DHF is a poorly treated medical condition that is characterized by the inability of the heart to relax properly and fill with blood, due to stiffening (glycation) of the heart and subsequent impaired relaxation of the left ventricle. Diastolic dysfunction is estimated to account for 30% to 50% of all heart failure cases, which total nearly five million cases in the U.S. alone.

In this Phase II clinical trial, DHF patients who received ALT-711 for 16 weeks experienced a statistically significant reduction in left ventricular mass. The patients also had a marked improvement in left ventricular diastolic filling. Additionally, the drug had a positive effect on patients' quality of life, as measured by a well-established heart failure/quality of life questionnaire. This Phase II trial is ongoing, and additional analyses of the data are being conducted. Here is a quote about the significance of this study:

"ALT-711 offers promise as a novel therapy for diastolic heart failure because currently available therapies do not specifically target the stiffening heart and vessel walls caused by pathological glucose-protein matrixes called Advanced Glycosylation End-product (A.G.E.) Crosslinks. The formation of A.G.E. Crosslinks is a natural part of the aging process that can lead to stiffening and loss of function in tissues, organs and vessels including the heart and large arteries. In previous human clinical testing, ALT-711 has shown the ability to restore elasticity to blood vessel walls by cleaving A.G.E. Crosslinks.* Additionally, in several preclinical studies ALT-711 has been shown to normalize the thickening of the left ventricle and remodel the heart."**

(Please note that these researchers use the term Advanced Glycosylation End-product (A.G.E.), which is another way of stating advanced glycation end products or "glycotoxins".)

Life Extension has long argued that the high cost of gaining FDA-approval denies Americans access to life-saving compounds such as ALT-711.*** It can take so long for a new compound to become an approved "drug", that many companies run out of capital before they are able to comply with the FDA's Byzantine regulatory procedures. The result is that Americans die even though potentially effective therapies sit in the FDA's waiting room.

Since we cannot yet reverse the pathological effects of glycation, it becomes critical for those seeking to prevent premature aging to at least slow this lethal process. Avoiding foods cooked at high temperature and supplementing with 1000 mg a day of carnosine are the best ways of mitigating the glycation process.

*Wolffenbuttel BH, et al. Breakers of advanced glycation end products restore large artery properties in experimental diabetes. Proc Natl Acad Sci USA, 1998 Apr 14;958:4630-4.
**Veronesi M et al. ALT-711, A collagen cross-link breaker, decreases myocardial fibrosis and improves endothelial dysfunction in hypertensive Dahl salt rats. American Heart Association 55th Annual Fall Conference and Scientific Sessions of the Council for High Blood Pressure Research, September 2001.
***Kanda T. C-reactive protein (CRP) in the cardiovascular system. Rinsho Byori 2001 Apr;49(4):395-401.

What you should do

Most Life Extension members follow a healthy lifestyle that helps prevent glycation and chronic inflammation.

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Inflammatory cytokine production can be suppressed with the proper supplementation of fish oil, DHEA, vitamin K and nettle leaf extract. If blood tests reveal persistently high levels of inflammatory cytokines, then 400 mg twice a day of a low-cost drug called pentoxiphylline may bring inflammatory cytokine levels down to safe ranges.

What one eats plays a major role in chronic inflammatory processes. Consuming low glycemic foods reduces the insulin surge that contributes to chronic inflammatory processes. It is also important to avoid over consumption of foods high in arachidonic acid (beef, egg yolk, dairy, etc.).

We now know that eating too much over cooked food causes an increase in inflammatory cytokines. Since most "junk" foods are cooked at extremely high temperatures, it makes sense to avoid french fries, hamburgers, potato chips, fried food and other snacks. These foods not only contain lots of glycotoxins, but they also create other metabolic disorders that can induce degenerative disease.

Consuming at least 1000 mg a day of carnosine, and/or 300 mg of the European drug aminoguanidine can inhibit pathological glycation reactions in the body. Avoiding foods cooked at high temperature not only reduces pathological glycation processes, but also prevents the formation of numerous gene-mutating toxins that are known carcinogens.

When food is cooked at high temperatures, deadly gene-mutating toxins are created that increase human cancer risk. This warning has been communicated to readers of this publication for many years. Now that overheated food is associated with accelerated aging, health conscious individuals have an even greater incentive to pay attention to their diet. As a member of the Life Extension Foundation, you learn about documented methods of reducing disease risk years before the general public.


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Those concerned that they are already suffering from the effects of a chronic inflammatory disorder should turn to the next page to learn how they can measure and suppress lethal pro-inflammatory cytokines.

For longer life,

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William Faloon

Further Reading: Protecting against the lethal effects of chronic inflammation

Caution: Food is cooked to destroy bacteria and other pathogens that could cause a serious illness. It is important not to eat undercooked food, but avoiding food unnecessarily cooked at higher temperatures is desirable. Certain foods (like fried foods) have to cook at high temperatures. Health conscious people are increasingly avoiding fried foods because they are associated with many health risks.

Note: For more information about eating healthier, log on to www.lef.org and access the Obesity and Inflammation (Chronic) protocols listed under Health Concerns. Also refer to the January 2001 issue of Life Extension on this website and click the article Drugs That Inhibit Cox-2 May Cause Tissue Damage.


References

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2. Kanda T. C-reactive protein (CRP) in the cardiovascular system. Rinsho Byori 2001 Apr;49(4):395-401.

3. Smith DA et al. Serum levels of the antiinflammatory cytokine interleukin-10 are decreased in patients with unstable angina. Circulation 2001 Aug 14;104(7):746-9.

4. Speer P. New insights into the pathogenesis of pulmonary inflammation in preterm infants. Biol Neonate 2001;79(3-4):205-9.

5. Glabinski AR et al. CXC chemokine receptors expression during chronic relapsing experimental autoimmune encephalomyelitis. Ann N Y Acad Sci 2000;917:135-44.

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10. Willard LB, et al. Pathological and biochemical consequences of acute and chronic neuroinflammation within the basal forebrain cholinergic system of rats. Neuroscience 1999 Jan;88(1):193-200.

11. Van der Meide PH, et al. Cytokines and the immune response. Biotherapy 1996;8(3-4):243-9.

12. Blaser MJ. Hypotheses on the pathogenesis and natural history of Helicobacter pylori-induced inflammation. Gastroenterology 1992 Feb;102(2):720-7.

13. Cominelli F, et al. Interleukin-1 in the pathogenesis of and protection from inflammatory bowel disease. Biotherapy 1989;1(4):369-75.

14. Deon D, et al. Cross-talk between il-1 and il-6 signaling pathways in rheumatoid arthritis synovial fibroblasts. J Immunol 2001 Nov 1;167(9):5395-403.

15. Baynes JW, et al. Glycoxidation and lipoxidation in atherogenesis. Free Radic Bio. Med 28, 1708-1716 (2000).

16. Sell DR, et al. Longitudinal determination of skin collagen glycation and glycoxidation rates predicts early death in C57Bl/6NNIA mice. FASEB J 14,145-156 (2000).

17. Dyer DG, et al. The Maillard Reaction in vivo. Z Ernahrungswiss 30,29-45(1991).

18. Monnier VM, et al. Acelerated age-related browning of human collagen in diabetes mellitus. Proc Natl Acad Sci, USA 81,583-587(1984).

19. Monnier VM, et al. Skin collagen glycation, glycoxidation, and crosslinking are lower in subjects with long-term intensive versus conventional therapy of type 1 diabetes: relevance of glycated collagen products versus HbA1c as markers of diabetic complications. Diabetes 48, 870-880(1999).

20. Schmidt AM, et al. The multiligand receptor RAGE as a progression factor amplifying immune and inflammatory responses. J Clin Invest 108,949-955(2001).

21. [Don't have the authors] Role of Inflammatory and Hemostatic mediators in preclinical endothelial dysfunction: Relevance to high-risk patients with hypertension. JACC (Supplement A) 2002 Mar 6; 39 (5):p.209A.

22. Pradhan AD, et al. C-reactive protein, interleukin 6 and risk of developing type 2 diabetes mellitus. JAMA 2001;286:327-334.

23. Harris TB, et al. Associations of elevated interleukin-6 and C-reactive protein levels with mortality in the elderly. Am J Med 1999 May;106(5):506-12.

24. Walston J, et al. Frailty and activation of the inflammation and coagulation systems with and without clinical comorbidities; results from the cardiovascular health study. Archives of Internal Medicine (2002;162:2333-2341).

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