Life Extension Magazine
Top Ten Recommendations

1: Life Extension Mix

2: Life Extension Super Booster

3: Coenzyme Q10

4: Mitochondrial Energy Optimizer

5: Cognitex

6: Super EPA/DHA with Sesame Lignans

7: Enhanced Natural Prostate with Cernitin (Men)

7: Bone Restore (Women)

8: Restoring Youthful Hormone Balance

9: S-adenosyl-methionine (SAMe)

10: Aspirin

Recommendation: 4
Mitochondrial Energy Optimizer

DOSAGE: Two capsules, two times per day.

It is well established that free radical damage is a culprit behind premature aging.1 To counteract toxic free radicals, health conscious people supplement with antioxidants such as green tea, grape-seed, lycopene, gamma tocopherol, and other plant extracts.

Scientific studies have identified factors that contribute to age-related disorders in addition to free radicals. One of the most serious events that cause the loss of cellular vitality is the depletion of mitochondrial energy function. Cells require healthy mitochondrial activity to perform life-sustaining metabolic processes. As mitochondrial function weakens in our cells, so does the vitality of organs such as the heart and brain, or in some cases, the entire body.2-7

While coenzyme Q10 is necessary for youthful mitochondrial energy function, there are other essential nutrients involved in the mitochondria’s “respiratory chain.” In order for the mitochondria to create the energy needed to sustain cellular function, fatty acids (which serve as the mitochondria’s fuel) must be transported through the cell membrane and into the mitochondria.8-10 The amino acid acetyl-l-carnitine boosts mitochondrial energy production by facilitating fatty acid transport and oxidation within the cell.11-13

As the mitochondria burn fatty acids to produce cellular energy, it generates a host of free radicals in the process. That is why a mitochondrial antioxidant like lipoic acid is so critical. The new Mitochondrial Energy Optimizer provides a much more potent form of lipoic acid (called R-lipoic acid), along with a more effective form of carnitine called acetyl-l-carnitine arginate.

The new Mitochondrial Energy Optimizer incorporates the tremendous advances in our knowledge about the importance of maintaining mitochondrial integrity as we age. Scientists now know that mitochondrial decay in aging is a major driving force behind the aging process.2,5

All the cells in our bodies contain 300-400 tiny organelles called mitochondria that function to produce cellular energy by means of the ATP cycle. Mitochondria produce the vast majority of free radicals in our cells. Fatty acids that serve as the fuel for the mitochondria are pulled across the mitochondrial membrane by carnitine and other forms, like acetyl-l-carnitine.14,15 As we age, we lose the ability to pull fatty acids across the membrane because of membrane damage from this ‘blast furnace’ effect inside the mitochondria. From birth we have a 1-2% leakage of reactive oxygen species from the respiratory chain in the mitochondria that increases dramatically with age; generating huge amounts of free radicals.16 We call this leakage the “loss of respiratory control.”

The new Mitochondrial Energy Optimizer helps restore mitochondrial respiratory control by lowering natural antioxidant leakage and boosting cellular levels of R-lipoic acid, acetyl-l-carnitine, and endogenous antioxidant enzymes.

A New Brain Regeneration Nutrient
Brain cells communicate with each other because they are connected to one another by neurites (dendrites and axons). Neurites are long filament-like terminal branches of nerve cells that grow much like branches of a tree. Neurites function to provide the communication circuitry pathways between the nerve cells.

As we age, there is a loss of neurites, which results in slowed thinking as neural-connection pathways are reduced from many in number to only a few. The effect of the age-related neurite loss is that thought processing pathways, thinking time, and reaction times are all significantly diminished.

Acetyl-l-carnitine arginate is a patented form of carnitine that stimulates the growth of neurites in the brain. Studies show that acetyl carnitine arginate stimulates the growth of new neurites by an astounding 19.5% (similar to that of Nerve Growth Factor itself). Acetyl carnitine arginate acts together with acetyl carnitine to increase neurite outgrowth.17

Acetyl-l-carnitine by itself stimulates neurite growth after five days by 5.6%. Acetyl carnitine arginate, on the other hand, stimulates neurite outgrowth in the same time period by 19.5%…an increase of over three-fold!17

An equally impressive finding was the average length of the neurites produced by the acetyl-carnitine arginate is 21% longer than in the acetyl-l-carnitine-only group.17

When scientists compared the effects of acetyl-l-carnitine and arginine, the mixture gave the same growth results as acetyl carnitine by itself, i.e. 5.6%. This study showed that acetyl-l-carntine arginate induced 3.48 times more neurite growth compared to acetyl-l-carnitine mixed with arginine.17

Multiple Neurological Effects of Acetyl-l-Carnitine
The acetylated form of L-carnitine (acetyl-l-carnitine) facilitates the release and synthesis of acetylcholine by donating its acetyl group to the production of acetylcholine, an important neurotransmitter.18 Acetyl-l-carnitine also enhances the release of dopamine from neurons and helps it bind to dopamine receptors.19,20 Numerous human and animal studies validate the multiple beneficial mechanisms that acetyl-l-carnitine exerts in the brain.

Acetyl-l-carnitine is more effective than L-carnitine in carrying fatty acids across the membrane into the cell where they are burned as energy. Since 1995, Life Extension members have been supplementing with acetyl-l-carnitine and deriving the many benefits this form of carnitine has shown in published scientific studies.

Acetyl-l-carnitine and acetyl-l-carnitine arginate work particularly well together because of the high amount of free carnitine contained in the acetyl-l-carnitine. With the discovery of acetyl-l-carnitine arginate, the benefits of acetyl-l-carnitine can now be greatly augmented. The new Mitochondrial Energy Optimizer provides both acetyl-l-carnitine and acetyl-l-carnitine arginate.

Suppressing Mitochondria-Generated Free Radicals
Alpha lipoic acid is a particularly potent antioxidant because of its ability to boost glutathione levels inside cells to protect against mitochondrial-generated free radicals.21-27 Lipoic acid functions as a fat and water-soluble antioxidant.28 It easily crosses cell membranes to confer antioxidant protection to interior and exterior cellular structures.28,29

Most people don’t know that the active part of alpha lipoic acid is the “R”-lipoic acid’ isomer.28 R-lipoic acid, also referred to as “natural lipoic acid,” is found in very small amounts in the tissues and is tightly bound to mitochondrial complexes. Due to the difficulty of isolating R-lipoic, researchers originally conducted studies using only alpha lipoic acid.

Alpha lipoic acid contains 50% “R”-lipoic and 50% “S”-lipoic acids. While the body can utilize both forms of lipoic acid, the R-lipoic form is far more biologically active. For example, the “R”-form improves ATP synthesis in isolated cells, whereas the “S”-lipoic form does not. The R-lipoic acid form was shown to increase cell membrane fluidity and transport.30,31

As the biologically active form of the key “mitochondrial antioxidant” known as “alpha lipoic acid,” R-lipoic acid is directly involved in cellular metabolism. It is a vital component of the intracellular antioxidant cycle, able to scavenge a variety of free radicals and reactive oxygen species while recycling vitamins C, E and glutathione.31-36

“R”-lipoic acid readily crosses the blood brain barrier and has been shown effective for elevating intracellular glutathione levels.37 This biologically active lipoic acid isomer helps regulate neuronal calcium homeostasis,38,39 regulates pro-inflammatory cytokines,40-43 and alters the expression of ‘toxic genes.’44 “R”-lipoic acid has been used to protect against adverse glucose reactions in the body and recommended as a ‘neuroprotective agent.’37,45-47 Because “R”-lipoic is the naturally occurring form found in mitochondrial complexes, it offers substantially greater benefits at significantly lower doses than the synthetic forms of lipoic acid currently available.

The daily dose of the Mitochondrial Energy Optimizer provides 150 net milligrams of expensive R-lipoic acid, which provides more protection against free radicals than higher amounts of alpha lipoic acid.

A Powerful New Antioxidant
Three types of sprout concentrates—soy, corn and wheat—are added to the Mitochondrial Energy Optimizer to stimulate the endogenous production of antioxidant enzymes (such as superoxide dismutase (SOD) that increase energy output in mitochondria by further restoring respiratory control. Wheat sprout enzymes have been shown to increase serum and blood levels of SOD.48 The effects of increased SOD levels block inflammatory processes and provide relief from associated disorders.

Guarding Against Glycation
Aging causes irreversible damage to the body’s proteins. The underlying mechanism behind this damage is glycation. A simple definition of glycation is the cross-linking of proteins and sugars to form non-functioning structures in the body. The process of glycation can be superficially seen as unsightly wrinkled skin. Glycation is also an underlying cause of age-related calamities including the neurologic, vascular, and eye disorders.49-58 Carnosine is a multifunctional dipeptide that interferes with the glycation process.59-62 When compared to the anti-glycating drug aminoguanidine, carnosine has been shown to inhibit glycation earlier in the process.

Carnosine levels are reduced with age. Muscle levels decline 63% from age 10 to age 70, which may account for the normal age-related decline in muscle mass and function.60 Since carnosine acts as a pH buffer, it can keep on protecting muscle cell membranes from oxidation under the acidic conditions of muscular exertion. Carnosine enables the heart muscle to contract more efficiently through enhancement of calcium response in heart myocytes.63 Long-lived cells such as nerve cells (neurons) and muscle cells (myocytes) contain high levels of carnosine. Muscle levels of carnosine correlate with the maximum life spans of animals.

Carnosine is one of the few compounds that increase the life span of human cells in culture. Human fibroblasts divide 40 to 45 times before they become senescent. The presence of carnosine allows the cells to divide 8 to 10 times more before they stop dividing, increasing cell life span 20% or more.64-66 The daily dose of the Mitochondrial Energy Optimizer provides 1000 mg of carnosine.

Protecting Cells Against Glucose Toxicity
Benfotiamine and vitamin B1 act synergistically to prevent glucose from reacting with our proteins. Benfotiamine is simply a fat-soluble vitamin B-1 that helps inhibit the majority of complications by preventing glucose from reacting with kidneys, eyes, arteries, and other organs.67-70 The Mitochondrial Energy Optimizer contains the ideal potencies of benfotiamine and vitamin B1.

Improving Systemic Energy Levels
Rhodiola is an herb that has been shown to support mental well being, improve associative thinking, increase short-term memory, calculation, ability of concentration, and speed of audio-visual perception in several human double blind crossover studies.71-73

Rhodolia works primarily on the mitochondria in the central and parasympathetic nervous system. In small doses, rhodolia increases the bioelectric activity of the brain and stimulates norepinephrine, dopamine and serotonin, all major neurotransmitters.74

Every study with Rhodiola that shows positive effects uses the Russian Rhodiola standardized to 3% rosavins and 1% salidrosides. The Russian Rhodiola became so scarce because of demand, that many manufacturers began using the wrong species of Rhodiola or the wrong concentrations of active principals. Life Extension uses only the original Russian formulation that demonstrated the greatest efficacy in published substitute “reports” [studies].”74

Suppressing Inflammatory Cytokines
A great majority of studies investigating interleukin-6 (IL-6) show that higher levels of this cytokine are associated with many undesirable effects. A recent study of people who have reached or passed their 100th birthday reveals that they uniformly express lower than normal IL-6 levels.75

Luteolin is a flavonoid that is found in olive oil, green pepper, and perilla plant, and has been shown to lower pro-inflammatory cytokine expression in vitro and in vivo.76-78 In particular, luteolin is a strong IL-6 inhibitor that may work via several different mechanisms to reduce this lethal inflammatory cytokine. Some studies show that luteolin down regulates pro-inflammatory TNF-alpha activity to lower IL-6 levels. Others studies demonstrate that luteolin reduces NF-kappa B levels that control IL-6 production.79,80 Additional studies show that luteolin reduces across the board the majority of the most dangerous inflammatory factors in the body including NF-kappa Beta, TNF-alpha, IL-4, IL-5, and IL-6.79-81

The upregulation of inflammatory genes is one of the cruelest aspects of the aging process. Luteolin is an ideal supplement that is orally very effective as a potent inhibitor of IL-6 and related inflammatory cytokines at low doses. The new Mitochondrial Energy Optimizer provides 8 mg of standardized luteolin per daily dose.

Life Extension members can be assured that they now have access to the highest quality maximum strength, state-of-the-art, antiaging, and energy-restoring mitochondrial supplement in the world—the Mitochondrial Energy Optimizer. Here is the complete formula that only requires four capsules per day:

Acetyl-l-carnitine arginate HCl

750 mg

Acetyl-l-carnitine HCl

750 mg

Carnosine

1000 mg

R-lipoic acid

150 mg

Benfotiamine

150 mg

Vitamin B1

50 mg

Rhodiola rosea

150 mg

Luteolin

8 mg

Sprout concentrates

300 mg

The cost of taking all of the individual ingredients found in the new Mitochondrial Energy Optimizer would be prohibitive for most people. Members save huge dollars by stocking up on this comprehensive formula during the annual SUPER SALE.

Compared to the Chronoforte formula that requires six capsules per day, the Mitochondrial Energy Optimizer (that only requires four capsules) represents a substantial savings. To order the new Mitochondrial Energy Optimizer, call 1-800-544-4440.

Note: It is important to take four capsules per day of the Mitochondrial Energy Optimizer in order to benefit from carnosine. The reason is the body automatically metabolizes lower amounts of carnosine into an inert substance, but the body cannot neutralize the amount of carnosine (1000 mg) contained in four capsules of Mitochondrial Energy Optimizer. Please be advised that Chronoforte is still available for those who want to continue using this particular formula.

More Info on Mitochondrial Energy Optimizer

  Continue to Next Product
References

1. Beckman KB, Ames BN. The free radical theory of aging matures. Physiol Rev. 1998Apr;78(2):547-81. http://physrev.physiology.org/cgi/content/full/78/2/547

2. Ames BN. Delaying the mitochondrial decay of aging. Ann N Y Acad Sci. 2004 Jun;1019:406-11.

3. Harman D. Free radical theory of aging: a consequences of mitochondrial aging. Age 1983 6:86-94.

4. Miquel J, Fleming JE. A two step hypothesis on the mechanisms of in vitro cell aging: cell differentiation followed by intrinsic mitochondrial mutagenesis. Exp. Gerontol. 1984 19: 31-6.

5. Shigenaga MK, Hagen TM, Ames BN. Oxidative damage and mitochondrial decay in aging. Proc Natl Acad Sci USA 1994 91:10771-8.

6. Hagen TM., Yowe DL, Bartholomew JC., et al. Mitochondrial decay in hepatocytes from old rats: membrane potential declines, heterogeneity and oxidants increase. Proc Natl Acad Sci USA 1997 94:3064-9.

7. Beckman KB., Ames BN., Mitochondrial aging: open questions. Ann NY Acad. Sci. 1998; 854:118-27.

8. Kerner J, Hoppel C. Fatty acid import into mitochondria. Biochim Biophys Acta. 2000 Jun 26;1486(1):1-17.

9. Turcotte LP. Role of fats in exercise. Types and quality. Clin Sports Med. 1999 Jul;18(3):485-98.

10. Jeukendrup AE, Saris WH, Wagenmakers AJ. Fat metabolism during exercise: a review. Part I: fatty acid mobilization and muscle metabolism. Int J Sports Med. 1998 May;19(4):231-44.

11. Aureli T, Miccheli A, Ricciolini R, et al. Aging brain: effect of acetyl-L-carnitine treatment on rat brain energy and phospholipid metabolism. A study by 31P and 1H NMR spectroscopy. Brain Res. 1990 Aug 27;526(1):108-12.

12. Ebeling P, Tuominen JA, Arenas J, et al. The association of acetyl-L-carnitine with glucose and lipid metabolism in human muscle in vivo: the effect of hyperinsulinemia. Metabolism. 1997 Dec;46(12):1454-7.

13. Paradies G, Ruggiero FM, Petrosillo G, et al. Carnitine-acylcarnitine translocase activity in cardiac mitochondria from aged rats: the effect of acetyl-L-carnitine. Mech Ageing Dev. 1995 Oct 13;84(2):103-12.

14. Hagen TM, Moreau R, Suh JH, Visioli F. Mitochondrial decay in the aging rat heart: evidence for improvement by dietary supplementation with acetyl-L-carnitine and/or lipoic acid. Ann N Y Acad Sci. 2002 Apr;959:491-507.

15. Bremer J. Carnitine—metabolism and functions. Physiol Rev. 1983 Oct;63(4):1420-80.

16. Yakes FM, Van Houten B. Mitochondrial DNA damage is more extensive and persists longer than nuclear DNA damage in human cells following oxidative stress. Proc Natl Acad Sci U S A. 1997 Jan 21;94(2):514-9.

17. Taglialatela G, Navarra D, Olivi A, et al. Neurite outgrowth in PC12 cells stimulated by acetyl-L-carnitine arginine amide. Neurochem Res. 1995 Jan;20(1):1-9.

18. Ando S, Tadenuma T, Tanaka Y, et al. Enhancement of learning capacity and cholinergic synaptic function by carnitine in aging rats. J Neurosci Res. 2001 Oct 15;66(2):266-71.

19. Sershen H, Harsing LG Jr, Banay-Schwartz M, et al. Effect of acetyl-L-carnitine on the dopaminergic system in aging brain. J Neurosci Res. 1991 Nov;30(3):555-9.

20. Harsing LG Jr, Sershen H, Toth E, et al. Acetyl-L-carnitine releases dopamine in rat corpus striatum: an in vivo microdialysis study. Eur J Pharmacol. 1992 Jul 21;218(1):117-21.

21. Smith AR, Shenvi SV, Widlansky M, et al. Lipoic acid as a potential therapy for chronic diseases associated with oxidative stress. Curr Med Chem. 2004 May;11(9):1135-46.

22. Biewenga GP, Haenen GR, Bast A. The pharmacology of the antioxidant lipoic acid. Gen Pharmacol. 1997 Sep;29(3):315-31.

23. Xu DP, Wells WW. alpha-lipoic acid dependent regeneration of ascorbic acid from dehydroascorbic acid in rat liver mitochondria. J Bioenerg Biomembr. 1996 Feb;28(1):77-85.

24. Arivazhagan P, Ramanathan K, Panneerselvam C. Effect of DL-alpha-lipoic acid on glutathione metabolic enzymes in aged rats. Exp Gerontol. 2001 Dec;37(1):81-7.

25. Suh JH, Wang H, Liu RM, et al. (R)-alpha-lipoic acid reverses the age-related loss in GSH redox status in post-mitotic tissues: evidence for increased cysteine requirement for GSH synthesis. Arch Biochem Biophys. 2004 Mar;1;423(1):126-35.

26. Kagan VE, Kuzmenko AI, Shvedova AA, et al. Direct evidence for recycling of myeloperoxidase-catalyzed phenoxyl radicals of a vitamin E homologue, 2,2,5,7,8-pentamethyl-6-hydroxy chromane, by ascorbate/dihydrolipoate in living HL-60 cells. Biochim Biophys Acta. 2003 Mar 17;1620(1-3):72-84.

27. Stoyanovsky DA, Goldman R, Darrow RM, et al. Endogenous ascorbate regenerates vitamin E in the retina directly and in combination with exogenous dihydrolipoic acid. Curr Eye Res. 1995 Mar;14(3):181-9.

28. Kagan VE, Shvedova A, Serbinova E, et al. Dihydrolipoic acid—a universal antioxidant both in the membrane and in the aqueous phase. Reduction of peroxyl, ascorbyl and chromanoxyl radicals. Biochem Pharmacol. 1992 Oct 20;44(8):1637-49.

29. Wollin SD, Jones PJ. Alpha-lipoic acid and cardiovascular disease. J Nutr. 2003 Nov;133(11):3327-30.

30. Zimmer G, Beikler TK, Schneider M, et al. Dose/response curves of lipoic acid R-and S-forms in the working rat heart during reoxygenation: superiority of the R-enantiomer in enhancement of aortic flow. J Mol Cell Cardiol. 1995 Sep;27(9):1895-903.

31. Assadnazari H, Zimmer G, Freisleben HJ, et al. Cardioprotective efficiency of dihydrolipoic acid in working rat hearts during hypoxia and reoxygenation. 31P nuclear magnetic resonance investigations. Arzneimittelforschung. 1993 Apr;43(4):425-32.

32. Gotz ME, Dirr A, Burger R, et al. Effect of lipoic acid on redox state of coenzyme Q in mice treated with 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine and diethyldithiocarbamate. Eur J Pharmacol. 1994 Feb 15;266(3):291-300.

33. Lykkesfeldt J, Hagen TM, Vinarsky V, et al. Age-associated decline in ascorbic acid concentration, recycling, and biosynthesis in rat hepatocytes—reversal with (R)-alpha-lipoic acid supplementation. FASEB J. 1998 Sep;12(12):1183-9.

34. Suh JH, Shenvi SV, Dixon BM, et al. Decline in transcriptional activity of Nrf2 causes age-related loss of glutathione synthesis, which is reversible with lipoic acid. Proc Natl Acad Sci U S A. 2004 Mar 9;101(10):3381-6.

35. Kozlov AV, Gille L, Staniek K, et al. Dihydrolipoic acid maintains ubiquinone in the antioxidant active form by two-electron reduction of ubiquinone and one-electron reduction of ubisemiquinone. Arch Biochem Biophys. 1999 Mar 1;363(1):148-54.

36. Schneider D, Elstner EF. Coenzyme Q10, vitamin E, and dihydrothioctic acid cooperatively prevent diene conjugation in isolated low-density lipoprotein. Antioxid Redox Signal. 2000 Summer;2(2):327-33.

37. Prehn JH, Karkoutly C, Nuglisch J, et al. Dihydrolipoate reduces neuronal injury after cerebral ischemia. J Cereb Blood Flow Metab. 1992 Jan;12(1):78-87.

38. Sen CK, Roy S, Han D, Packer L. Regulation of cellular thiols in human lymphocytes by alpha-lipoic acid: a flow cytometric analysis. Free Radic Biol Med. 1997;22(7):1241-57.

39. Greenamyre JT, Garcia-Osuna M, Greene JG. The endogenous cofactors, thioctic acid and dihydrolipoic acid, are neuroprotective against NMDA and malonic acid lesions of striatum. Neurosci Lett. 1994 Apr 25;171(1-2):17-20.

40. Burkart V, Koike T, Brenner HH, et al. Dihydrolipoic acid protects pancreatic islet cells from inflammatory attack. Agents Actions. 1993 Jan;38(1-2):60-5.

41. Fuchs J, Milbradt R. Antioxidant inhibition of skin inflammation induced by reactive oxidants: evaluation of the redox couple dihydrolipoate/lipoate. Skin Pharmacol. 1994;7(5):278-84.

42. Mervaala E, Finckenberg P, Lapatto R, et al. Lipoic acid supplementation prevents angiotensin II-induced renal injury. Kidney Int. 2003 Aug;64(2):501-8.

43. Cho YS, Lee J, Lee TH, et al. alpha-Lipoic acid inhibits airway inflammation and hyperresponsiveness in a mouse model of asthma. J Allergy Clin Immunol. 2004 Aug;114(2):429-35.

44. Mizuno M, Packer L. Effects of alpha-lipoic acid and dihydrolipoic acid on expression of proto-oncogene c-fos. Biochem Biophys Res Commun. 1994 Apr 29;200(2):1136-42.

45. Estrada D.E.; Volchuk A.; Ramlal T.; Tritschler H.J.; Klip A. Stimulation of glucose uptake and translocation of glucose transporters in muscle cells by lipoic acid (thioctic acid) Diabetes und Stoffwechsel (Germany) 1996, 5/3 SUPPL. (41-45)

46. Henriksen EJ, Saengsirisuwan V. Exercise training and antioxidants: relief from oxidative stress and insulin resistance. Exerc Sport Sci Rev. 2003 Apr;31(2):79-84.

47. Liu J, Head E, Gharib AM, et al. Memory loss in old rats is associated with brain mitochondrial decay and RNA/DNA oxidation: partial reversal by feeding acetyl-L-carnitine and/or R-alpha -lipoic acid. Proc Natl Acad Sci U S A. 2002 Feb 19;99(4):2356-61.Erratum in: Proc Natl Acad Sci U S A 2002 May 14;99(10):7184-5.

48. Calzuola I, Marsili V, Gianfranceschi GL. Synthesis of antioxidants in wheat sprouts. J Agric Food Chem. 2004 Aug 11;52(16):5201-6.

49. Kessel L, Hougaard JL, Sander B, et al. Lens ageing as an indicator of tissue damage associated with smoking and non-enzymatic glycation—a twin study. Diabetologia. 2002 Oct;45(10):1457-62. Epub 2002 Sep 05.

50. Robert L, Robert AM. Aging, from basic research to pathological applications. Pathol Biol (Paris). 2003 Dec;51(10):543-9.

51. Kikuchi S, Shinpo K, Takeuchi M, et al. Glycation—a sweet tempter for neuronal death. Brain Res Brain Res Rev. 2003 Mar;41(2-3):306-23.

52. DeGroot J, Verzijl N, Wenting-van Wijk MJ, et al. Accumulation of advanced glycation end products as a molecular mechanism for aging as a risk factor in osteoarthritis. Arthritis Rheum. 2004 Apr;50(4):1207-15.

53. Krone CA, Ely JT. Ascorbic acid, glycation, glycohemoglobin and aging. Med Hypotheses. 2004;62(2):275-9.

54. Saari JT. Copper deficiency and cardiovascular disease: role of peroxidation, glycation, and nitration. Can J Physiol Pharmacol. 2000 Oct;78(10):848-55.

55. Yim MB, Yim HS, Lee C, et al. Protein glycation: creation of catalytic sites for free radical generation. Ann N Y Acad Sci. 2001 Apr;928:48-53.

56. Verzijl N, DeGroot J, Ben ZC, et al. Crosslinking by advanced glycation end products increases the stiffness of the collagen network in human articular cartilage: a possible mechanism through which age is a risk factor for osteoarthritis. Arthritis Rheum. 2002 Jan;46(1):114-23.

57. Wondrak GT, Roberts MJ, Jacobson MK, et al. Photosensitized growth inhibition of cultured human skin cells: mechanism and suppression of oxidative stress from solar irradiation of glycated proteins. J Invest Dermatol. 2002 Aug;119(2):489-98.

58. Tsuru M, Nagata K, Jimi A, et al. Effect of AGEs on human disc herniation: intervertebral disc hernia is also effected by AGEs. Kurume Med J. 2002;49(1-2):7-13.

59. Seidler NW, Yeargans GS, Morgan TG. Carnosine disaggregates glycated alpha-crystallin: an in vitro study. Arch Biochem Biophys. 2004 Jul 1;427(1):110-5.

60. Stuerenburg HJ. The roles of carnosine in aging of skeletal muscle and in neuromuscular diseases. Biochemistry (Mosc). 2000 Jul;65(7):862-5. Full text article: http://protein.bio.msu.su/biokhimiya/contents/v65/full/65071013.htm

61. Hipkiss AR, Brownson C, Bertani MF, Ruiz E, Ferro A. Reaction of carnosine with aged proteins: another protective process? Ann N Y Acad Sci. 2002 Apr;959:285-94.

62. Ukeda H, Hasegawa Y, Harada Y, Sawamura M. Effect of carnosine and related compounds on the inactivation of human Cu,Zn-superoxide dismutase by modification of fructose and glycolaldehyde. Biosci Biotechnol Biochem. 2002 Jan;66(1):36-43.

63. Zaloga GP, Roberts PR, Black KW, et al. Carnosine is a novel peptide modulator of intracellular calcium and contractility in cardiac cells. Am J Physiol. 1997 Jan;272(1 Pt 2):H462-8.

64. Hipkiss AR. Carnosine, a protective, anti-ageing peptide? Int J Biochem Cell Biol. 1998 Aug;30(8):863-8.

65. McFarland GA, Holliday R. Further evidence for the rejuvenating effects of the dipeptide L-carnosine on cultured human diploid fibroblasts. Exp Gerontol. 1999 Jan;34(1):35-45.

66. Holliday R, McFarland GA. A role for carnosine in cellular maintenance. Biochemistry (Mosc). 2000 Jul;65(7):843-8.

67. Simeonov S, Pavlova M, Mitkov M, Mincheva L, Troev D. Therapeutic efficacy of “Milgamma” in patients with painful diabetic neuropathy. Folia Med (Plovdiv). 1997;39(4):5-10.

68. Sadekov RA, Danilov AB, Vein AM. Diabetic polyneuropathy treatment by milgamma-100 preparation. Zh Nevrol Psikhiatr Im S S Korsakova. 1998;98(9):30-2 (in Russian).

69. Hammes HP, Du X, Edelstein D, et al. Benfotiamine blocks three major pathways of hyperglycemic damage and prevents experimental diabetic retinopathy. Nat Med. 2003 Mar;9(3):294-9. Epub 2003 Feb 18.

70. Stracke H, Lindemann A, Federlin K. A benfotiamine-vitamin B combination in treatment of diabetic polyneuropathy. Exp Clin Endocrinol Diabetes. 1996;104(4):311-6.

71. Shevtsov VA, Zholus BI, Shervarly VI, et al. A randomized trial of two different doses of a SHR-5 Rhodiola rosea extract versus placebo and control of capacity for mental work. Phytomedicine. 2003 Mar;10(2-3):95-105.

72. Darbinyan V, Kteyan A, Panossian A, et al. Rhodiola rosea in stress induced fatigue—a double blind cross-over study of a standardized extract SHR-5 with a repeated low-dose regimen on the mental performance of healthy physicians during night duty. Phytomedicine. 2000 Oct;7(5):365-71.

73. Spasov AA, Wikman GK, Mandrikov VB, et al. A double-blind, placebo-controlled pilot study of the stimulating and adaptogenic effect of Rhodiola rosea SHR-5 extract on the fatigue of students caused by stress during an examination period with a repeated low-dose regimen. Phytomedicine. 2000 Apr;7(2):85-9.

74. Richard P, Brown, MD, Patricia L. et al. Rhodiola rosea: A Phytomedicinal Overview. HerbalGram. 2002;56:40-52 © American Botanical Council http://www.herbalgram.org/herbalgram/articleview.asp?a=2333)

75. Louet S. Centenarians provide genetic clue to age-related disease.Drug Discov Today. 2003 Apr 1;8(7):280-1.

76. Chen CC, Chow MP, Huang WC, et al. Flavonoids inhibit tumor necrosis factor-alpha-induced up-regulation of intercellular adhesion molecule-1 (ICAM-1) in respiratory epithelial cells through activator protein-1 and nuclear factor-kappaB: structure-activity relationships. Mol Pharmacol. 2004 Sep;66(3):683-93.

77. Ueda H, Yamazaki C, Yamazaki M. Luteolin as an anti-inflammatory and anti-allergic constituent of Perilla frutescens. Biol Pharm Bull. 2002 Sep;25(9):1197-202.

78. Xagorari A, Papapetropoulos A, Mauromatis A, et al. Luteolin inhibits an endotoxin-stimulated phosphorylation cascade and proinflammatory cytokine production in macrophages. J Pharmacol Exp Ther. 2001 Jan;296(1):181-7.

79. Kotanidou, A. Luteolin reduces lipopolysaccharide-induced lethal toxicity and expression of proinflammatory molecules in mice. Am. J. Respir. Crit. Care Med. Mar 15; 165(6):818-23. 2002.

80. Kimata, M. Effects of luteolin and other flavenoids on IgE-mediated allergic reactions. Planta Med. Feb; 66(1): 25-9. 2000.

81. Surh, Y.J., Chun, K.S. Molecular mechanisms underlying chemopreventive activities of anti-inflammatory phytochemicals: downregulation of Cox-2 and Inos through suppression of NFkappaB activation. Mut. Res. 2001;480:243-68.

 
Free Subscription Offer

Health Concerns
Products
Abstracts
Get Your FREE Nutritional Supplement Guide