Life Extension Magazine February 2005
Promoting Mitochondrial Health Nutrients That Optimize Cellular Energy
By Dale Kiefer
By Dale Kiefer
Rhodiola: A Natural Energy Booster
Rhodiola rosea, also known as golden root or Arctic root, has garnered significant attention in recent years. Although still largely unfamiliar to Westerners, it has been used in traditional medicine for centuries and has been studied extensively by Russian scientists, who have dubbed it an “adaptogen.” This term refers to this herb’s remarkable ability to increase resistance to numerous chemical, physical, and biological stressors, including strenuous exercise, mental strain, and toxic chemicals.67
Studies have shown that rhodiola enhances exercise endurance, reduces fatigue under stressful conditions, and exerts an anti-inflammatory effect.68-72 Richard Brown, MD, assistant professor of clinical psychiatry at Columbia University and author of The Rhodiola Revolution, recommends it as an energy booster and treatment for depression, chronic fatigue, and anxiety.73
In a randomized, double-blind, placebo-controlled clinical trial on human subjects, Russian researchers showed that rhodiola extract improves the capacity to perform mentally demanding tasks under conditions of excess stress and fatigue. “The study showed a pronounced anti-fatigue effect... [that] was statistically highly significant,” the research team concluded.70 A similar controlled trial conducted on students during a “stressful examination period” found that objective and subjective measures of physical and mental performance were significantly superior among subjects who took rhodiola extract compared to those of subjects who took placebo.72
In 2004, Belgian researchers published the results of a randomized, double-blind, placebo-controlled study of rhodiola’s effects on endurance exercise performance. They concluded, “Acute rhodiola intake can improve endurance exercise capacity in young healthy volunteers.” This effect was not altered by prior daily intake of rhodiola for four weeks.69 It is believed that rhodiola’s many beneficial properties stem from its ability to influence the activities and levels of brain chemicals such as serotonin and norepinephrine, as well as of natural “feel good” opioids such as beta-endorphins.67,74
Luteolin Enhances Immune Response
Luteolin is a natural plant flavonoid found in herbs and vegetables, including parsley, olive oil, rosemary, and celery. Among its numerous benefits are modulation of the immune response and neutralization of free radicals.9,75 It has been shown to inhibit immune system chemicals implicated in the development and propagation of allergic disease, including pro-inflammatory interleukin-4 and interleukin-13.75 Likewise, luteolin protects the body from the development of cancer by inhibiting the activation of nuclear transcription factor-kappa beta induced by tumor necrosis factor-alpha, and by sensitizing tumor cells to apoptosis, or programmed cell death.76-78
Luteolin has even been suggested as a treatment for asthma. Indian researchers have shown that luteolin reduces some of the inflammatory processes responsible for the airway constriction associated with asthma.79 Even more interesting, Chinese researchers recently demonstrated that luteolin binds with the surface spike proteins on the deadly virus, blocking its entry into the host cell. In essence, say the researchers, luteolin may represent an effective means of developing new drugs for the prevention of viral infections such as the human immunodeficiency virus (HIV), hepatitis C, and severe acute respiratory syndrome (SARS).80
Wheat Sprout Enzymes: Antioxidant and Antimutagenic
Wheat sprout enzymes are another source of bioactive plant flavonoids. Their potential benefits may range from improving symptoms of fibromyalgia and joint pain to increasing energy and relieving symptoms of chronic fatigue
syndrome. These benefits are likely related to the presence of several potent natural antioxidant enzymes, including superoxide dismutase (SOD), glutathione peroxidase, and catalase.
Scientists have known for a number of years that inflammatory diseases are often associated with a decrease in some of these antioxidant enzymes. For example, Korean researchers recently demonstrated that the activity of superoxide dismutase and glutathione peroxidase is significantly lower among rheumatoid arthritis patients than among control subjects. Dietary intake of antioxidants was lower among the arthritis patients than among controls, researchers discovered.81
Their finding echoes conclusions reached by other researchers. Stanford University scientists, for instance, recently reported on the association between the presence of superoxide anion and the development of a wide range of degenerative diseases, including athero- sclerosis, stroke, heart attack, and chronic and acute inflammatory conditions.82 Pro-inflammatory superoxide anion is scavenged and neutralized by superoxide dismutase.
University of Pittsburgh scientists recently noted that overproduction of reactive oxygen species is associated with the development of cardiovascular disease, neurological disorders, and lung pathologies, among other conditions. Superoxide dismutase that operates outside cells, in the extracellular matrix, “. . . is ideally situated to prevent cell and tissue damage initiated by extracellularly produced [reactive oxygen species],” according to the research team.83 More recently, a Texas neuroscience researcher noted that persistent, chronic pain associated with inflammation appears to be mediated by superoxide, and experiments have shown that neutralizing superoxide decreases pain.84
The relationship among superoxide, superoxide dismutase, and disease processes is so compelling that scientists attempted years ago to intervene in diseases such as osteoarthritis by injecting superoxide dismutase derived from livestock blood cells directly into diseased joints. While the relief from inflammation was often dramatic, the technique is somewhat impractical and has not been embraced as a treatment for human patients.85
Soy, corn, and wheat sprouts, on the other hand, may represent a more acceptable means of increasing one’s levels of natural antioxidant enzymes. Italian researchers recently published an analysis of the antioxidant content of wheat sprout extract, noting, “catalase and peroxidase activity appears very strong... ”86 They also reported, “it is evident that wheat sprout biologically active substances can be at least partially absorbed during the digestion process.”86 Another team of Italian scientists compared the antioxidant activity of wheat sprout extract to known pure antioxidants such as ascorbic acid, quercetin, and reduced glutathione. They concluded, “oxygen superoxide scavenging activity performed by wheat sprout extracts... is comparable to that shown by... pure compounds.”87
Research has likewise demonstrated that sprout enzymes also possess powerful antimutagenic properties (that is, they prevent mutations that may lead to the development of cancers).88,89 According to unpublished data compiled by researchers at the University of Hawaii, a survey of 120 subjects who ingested large amounts of plant-based antioxidant enzymes revealed that 88% reported increased energy, while 72% reported feeling stronger. Eighty-two percent of survey respondents reported feeling better over all after supplementing with sprout-derived antioxidants.90
Successful aging depends on maintaining a constant, abundant supply of cellular energy. To ensure a continuous supply of energy in the body, it is crucial to support the health of the mitochondria, the power plants of each cell. Nutrients such as lipoic acid and acetyl-L-carnitine have been shown to improve mitochondrial function and boost diminished energy levels. A derivative of acetyl-L-carnitine, acetyl-L-carnitine arginate, has demonstrated additional benefits in supporting brain health and fighting senescence.
Other nutritional and plant-based remedies offer complementary support in the fight against age-related degeneration. Carnosine helps to prevent glycation reactions that are associated with the dysfunction of proteins and enzymes, and can lead to wrinkles, vision changes, and kidney disease. Benfotiamine, a powerful cousin of vitamin B1, helps promote healthy blood glucose levels, a critically important aspect of optimal aging. Plants such as rhodiola, and plant extracts such as luteolin and wheat sprout enzymes, help improve the body’s resistance to stressors, relieving fatigue and promoting well being.
Together, these nutrients and plant remedies offer great protection from the wear and tear of time and stress, while supplying the age-defying energy needed for optimal health.
1. Dufour E, Larsson NG. Understanding aging: revealing order out of chaos. Biochim Biophys Acta. 2004 Jul 23;1658(1-2):122-32.
2. Alexeyev MF, Ledoux SP, Wilson GL. Mitochondrial DNA and aging. Clin Sci (Lond). 2004 Oct;107(4):355-64.
3. Gadaleta MN, Cormio A, Pesce V, Lezza AM, Cantatore P. Aging and mitochondria. Biochimie. 1998 Oct;80(10):863-70.
4. Liu J, Atamna H, Kuratsune H, Ames BN. Delaying brain mitochondrial decay and aging with mitochondrial antioxidants and metabolites. Ann NY Acad Sci. 2002 Apr;959:133-66.
5. Hagen TM, Liu J, Lykkesfeldt J, et al. Feeding acetyl-L-carnitine and lipoic acid to old rats significantly improves metabolic function while decreasing oxidative stress. Proc Natl Acad Sci USA. 2002 Feb 19;99(4):1870-5.
6. Zhang WJ, Frei B. Alpha-lipoic acid inhibits TNF-alpha-induced NF-kappaB activation and adhesion molecule expression in human aortic endothelial cells. FASEB J. 2001 Nov;15(13):2423-32.
7. Suh JH, Shigeno ET, Morrow JD. et al. Oxidative stress in the aging rat heart is reversed by dietary supplementation with (R)-(alpha)-lipoic acid. FASEB J. 2001 Mar;15(3):700-6.
8. Hagen TM, Ingersoll RT, Lykkesfeldt J, et al. (R)-alpha-lipoic acid-supplemented old rats have improved mitochondrial function, decreased oxidative damage, and increased metabolic rate. FASEB J. 1999 Feb;13(2):411-8.
9. Scorziello A, Meucci O, Calvani M, Schettini G. Acetyl-L-carnitine arginine amide prevents beta 25-35-induced neurotoxicity in cerebellar granule cells. Neurochem Res. 1997 Mar;22(3):257-65.
10. 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.
11. Horvathova K, Novotny L, Vachalkova A. The free radical scavenging activity of four flavonoids determined by the comet assay. Neoplasma. 2003;50(4):291-5.
12. Virmani A, Binienda Z. Role of carnitine esters in brain neuropathology. Mol Aspects Med. 2004 Oct;25(5-6):533-49.
13. McDaniel MA, Maier SF, Einstein GO. “Brain-specific” nutrients: a memory cure? Nutrition. 2003 Nov;19(11-12):957-75.
14. Bianchetti A, Rozzini R, Trabucchi M. Effects of acetyl-L-carnitine in Alzheimer’s disease patients unresponsive to acetyl cholinesterase inhibitors. Curr Med Res Opin. 2003;19(4):350-3.
15. Brooks JO, III, Yesavage JA, Carta A, Bravi D. Acetyl L-carnitine slows decline in younger patients with Alzheimer’s disease: a reanalysis of a double-blind, placebo-con- trolled study using the trilinear approach. Int Psychogeriatr. 1998 Jun;10(2):193-203.
16. Montgomery SA, Thal LJ, Amrein R. Meta-analysis of double blind randomized controlled clinical trials of acetyl-L-carnitine versus placebo in the treatment of mild cog- nitive impairment and mild Alzheimer’s disease. Int Clin Psychopharmacol. 2003 Mar;18(2):61-71.
17. Tanaka Y, Sasaki R, Fukui F, et al. Acetyl-L-carnitine supplementation restores decreased tissue carnitine levels and impaired lipid metabolism in aged rats. J Lipid Res. 2004 Apr;45(4):729-35.
18. Aureli T, Di Cocco ME, Capuani G, et al. Effect of long-term feeding with acetyl-L-carnitine on the age-related changes in rat brain lipid composition: a study by 31P NMR spectroscopy. Neurochem Res. 2000 Mar;25(3):395-9.
19. Sharman EH, Vaziri ND, Ni Z, Sharman KG, Bondy SC. Reversal of biochemical and behavioral parameters of brain aging by melatonin and acetyl-L-carnitine. Brain Res. 2002 Dec 13;957(2):223-0.
20. Hagen TM, Ingersoll RT, Wehr CM, et al. Acetyl-L-carnitine fed to old rats partially restores mitochondrial function and ambula- tory activity. Proc Natl Acad Sci USA. 1998 Aug 4;95(16):9562-6.
21. 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 USA. 2002 Feb 19;99(4):2356-61.
22. Seidman MD, Khan MJ, Bai U, Shirwany N, Quirk WS. Biologic activity of mitochondrial metabolites on aging and age-related hearing loss. Am J Otol. 2000 Mar;21(2):161-7.
23. Swamy-Mruthinti S, Carter AL. Acetyl-L-carnitine decreases glycation of lens pro- teins: in vitro studies. Exp Eye Res. 1999 Jul;69(1):109-15.
24. 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 NY Acad Sci. 2002 Apr;959:491-507.
25. Binienda ZK. Neuroprotective effects of L-carnitine in induced mitochondrial dysfunction. Ann NY Acad Sci. 2003 May;993:289-95.
26. Kuratsune H, Yamaguti K, Lindh G, et al. Brain regions involved in fatigue sensation: reduced acetylcarnitine uptake into the brain. Neuroimage. 2002 Nov;17(3):1256-65.
27. Pettegrew JW, Levine J, McClure RJ. Acetyl- L-carnitine physical-chemical, metabolic, and therapeutic properties: relevance for its mode of action in Alzheimer’s disease and geriatric depression. Mol Psychiatry. 2000 Nov;5(6):616-32.
28. Vaswani M, Linda FK, Ramesh S. Role of selective serotonin reuptake inhibitors in psychiatric disorders: a comprehensive review. Prog Neuropsychopharmacol Biol Psychiatry. 2003 Feb;27(1):85-102.
29. Bourin M, David DJ, Jolliet P, Gardier A. Mechanism of action of antidepressants and therapeutic perspectives. Therapie. 2002 Jul;57(4):385-96.
30. Westlund KN, Lu Y, Werrbach-Perez K, et al. Effects of nerve growth factor and acetyl- L-carnitine arginyl amide on the human neuronal line HCN-1A. Int J Dev Neurosci. 1992 Oct;10(5):361-73.
31. Ames BN. Delaying the mitochondrial decay of aging. Ann NY Acad Sci. 2004 Jun;1019:406-11.
32. 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):1895-1903.
33. Smith AR, Hagen TM. Vascular endothelial dysfunction in aging: loss of Akt-dependent endothelial nitric oxide synthase phosphory- lation and partial restoration by (R)-alpha- lipoic acid. Biochem Soc Trans. 2003 Dec;31(Pt 6):1447-9.
34. Smith AR, Shenvi SV, Widlansky M, Suh JH, Hagen TM. Lipoic acid as a potential therapy for chronic diseases associated with oxida- tive stress. Curr Med Chem. 2004 May;11(9):1135-46.
35. Thurich T, Bereiter-Hahn J, Schneider M, Zimmer G. Cardioprotective effects of dihydrolipoic acid and tocopherol in right heart hypertrophy during oxidative stress. Arzneimittelforschung. 1998 Jan;48(1):13-21.
36. Wollin SD, Jones PJ. Alpha-lipoic acid and cardiovascular disease. J Nutr. 2003 Nov;133(11):3327-30.
37. Packer L, Tritschler HJ, Wessel K. Neuroprotection by the metabolic antioxidant alpha-lipoic acid. Free Radic Biol Med. 1997;22(1-2):359-78.
38. Morini M, Roccatagliata L, Dell’Eva R, et al. Alpha-lipoic acid is effective in prevention and treatment of experimental autoimmune encephalomyelitis. J Neuroimmunol. 2004 Mar;148(1-2):146-53.
39. Ziegler D, Nowak H, Kempler P, Vargha P, Low PA. Treatment of symptomatic diabetic polyneuropathy with the antioxidant alpha- lipoic acid: a meta-analysis. Diabet Med. 2004 Feb;21(2):114-21.
40. Evans JL, Heymann CJ, Goldfine ID, Gavin LA. Pharmacokinetics, tolerability, and fructosamine-lowering effect of a novel, controlled-release formulation of alpha-lipoic acid. Endocr Pract. 2002 Jan;8(1):29-35.
41. No author. Thioctic acid. Notes Undergr. 1995 Apr;(no 30):2.
42. Duby JJ, Campbell RK, Setter SM, White JR, Rasmussen KA. Diabetic neuropathy: an intensive review. Am J Health Syst Pharm. 2004 Jan 15;61(2):160-73.
43. Melhem MF, Craven PA, Liachenko J, DeRubertis FR. Alpha-lipoic acid attenuates hyperglycemia and prevents glomerular mesangial matrix expansion in diabetes. J Am Soc Nephrol. 2002 Jan;13(1):108-16.
44. Sell DR, Monnier VM. Conversion of argi- nine into ornithine by advanced glycation in senescent human collagen and lens crystallins. J Biol Chem. 2004 Oct 15.
45. Sztanke K, Pasternak K. The Maillard reaction and its consequences for a living body. Ann Univ Mariae Curie Sklodowska [Med.] 2003;58(2):159-62.
46. Wautier JL and Schmidt AM. Protein glycation: a firm link to endothelial cell dysfunction. Circ Res. 2004 Aug 6;95(3):233-8.
47. Loeser RF, Jr. Aging cartilage and osteoarthritis—what’s the link? Sci Aging Knowledge Environ. 2004 Jul 21;2004(29):e31.
48. Seidler NW, Yeargans GS, Morgan TG. Carnosine disaggregates glycated alpha-crystallin: an in vitro study. Arch Biochem Biophys. 2004 Jul 1;427(1):110-15.
49. Wang AM, Ma C, Xie ZH, Shen F. Use of carnosine as a natural anti-senescence drug for human beings. Biochemistry (Mosc.) 2000 Jul;65(7):869-71.
50. Dukic-Stefanovic S, Schinzel R, Riederer P, Munch G. AGES in brain ageing: AGE- inhibitors as neuroprotective and antidementia drugs? Biogerontology. 2001;2(1):19-34.
51. Rofina JE, Singh K, Skoumalova-Vesela A, et al. Histochemical accumulation of oxidative damage products is associated with Alzheimer-like pathology in the canine. Amyloid. 2004 Jun;11(2):90-100.
52. Stuerenburg HJ, Kunze K. Concentrations of free carnosine (a putative membrane-protective antioxidant) in human muscle biopsies and rat muscles. Arch Gerontol Geriatr. 1999 Sep;29(2):107-13.
53. Boldyrev AA, Gallant SC, Sukhich GT. Carnosine, the protective, anti-aging peptide. Biosci Rep. 1999 Dec;19(6):581-7.
54. Kantha SS, Wada S, Tanaka H, et al. Carnosine sustains the retention of cell morphology in continuous fibroblast culture subjected to nutritional insult. Biochem Biophys Res Commun. 1996 Jun 14;223(2):278-82.
55. Gallant S, Semyonova M, Yuneva M. Carnosine as a potential anti-senescence drug. Biochemistry (Mosc.) 2000 Jul;65(7):866-8.
56. Hipkiss AR, Brownson C, Bertani MF, Ruiz E, Ferro A. Reaction of carnosine with aged proteins: another protective process? Ann NY Acad Sci. 2002 Apr;959:285-94.
57. Brownson C, Hipkiss AR. Carnosine reacts with a glycated protein. Free Radic Biol Med. 2000 May 15;28(10):1564-70.
58. Horning MS, Blakemore LJ, Trombley PQ. Endogenous mechanisms of neuroprotection: role of zinc, copper, and carnosine. Brain Res. 2000 Jan 3;852(1):56-61.
59. Hipkiss AR, Brownson C. Carnosine reacts with protein carbonyl groups: another possible role for the anti-ageing peptide? Biogerontology. 2000;1(3):217-23.
60. Victoroff J. Saving Your Brain: The Revolutionary Plan to Boost Brain Power, Improve Memory and Protect Yourself Against Aging and Alzheimer’s. New York: Bantam Books; 2002.
61. Flier JS. Diabetes. The missing link with obe- sity? Nature. 2001 Jan 18;409(6818):292-3.
62. Ott A, Stolk RP, van Harskamp F, et al. Diabetes mellitus and the risk of dementia: The Rotterdam Study. Neurology. 1999 Dec 10;53(9):1937-42.
63. Hammes HP, Du X, Edelstein D, et al. Benfotiamine blocks three major pathways of hyperglycemic damage and prevents experi- mental diabetic retinopathy. Nat Med. 2003 Mar;9(3):294-9.
64. Hammes HP, Hoerauf H, Alt A, et al. N(epsilon)(carboxymethyl)lysin and the AGE receptor RAGE colocalize in age-related macular degeneration. Invest Ophthalmol Vis Sci. 1999 Jul;40(8):1855-9.
65. Stitt AW. Advanced glycation: an important pathological event in diabetic and age related ocular disease. Br J Ophthalmol. 2001 Jun;85(6):746-53.
66. Bacher S, Schmitz ML. The NF-kappaB pathway as a potential target for autoimmune disease therapy. Curr Pharm Des. 2004;10(23):2827-37.
67. No authors. Rhodiola rosea. Monograph. Altern Med Rev. 2002 Oct;7(5):421-3.
68. Abidov M, Grachev S, Seifulla RD, Ziegenfuss TN. Extract of Rhodiola rosea radix reduces the level of C-reactive protein and creatinine kinase in the blood. Bull Exp Biol Med. 2004 Jul;138(1):63-4.
69. De Bock K, Eijnde BO, Ramaekers M, Hespel P. Acute Rhodiola rosea intake can improve endurance exercise performance. Int J Sport Nutr Exerc.Metab. 2004 Jun;14(3):298- 307.
70. 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.
71. Darbinyan V, Kteyan A, Panossian A, et al. Rhodiola rosea in stress induced fatigue—a double blind cross-over study of a standard ized 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.
72. Spasov AA, Wikman GK, Mandrikov VB, Mironova IA, Neumoin VV. 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 peri- od with a repeated low-dose regimen. Phytomedicine. 2000 Apr;7(2):85-9.
73. Brown RP, Gerbarg PL, Graham B. The Rhodiola Revolution: Transform Your Health with the Herbal Breakthrough of the 21st Century. Emmaus, PA: Rodale Books; 2004.
74. Kelly GS. Rhodiola rosea: a possible plant adaptogen. Altern Med Rev. 2001 Jun;6(3):293-302.
75. Hirano T, Higa S, Arimitsu J, et al. Flavonoids such as luteolin, fisetin and apigenin are inhibitors of interleukin-4 and interleukin-13 production by activated human basophils. Int Arch Allergy Immunol. 2004 Jun;134(2):135-40.
76. Shi RX, Ong CN, Shen HM. Luteolin sensitizes tumor necrosis factor-alpha-induced apoptosis in human tumor cells. Oncogene. 2004 Oct 7;23(46):7712-21.
77. Choi JS, Choi YJ, Park SH, Kang JS, Kang YH. Flavones mitigate tumor necrosis factor-alpha-induced adhesion molecule upregulation in cultured human endothelial cells: role of nuclear factor-kappa B. J Nutr. 2004 May;134(5):1013-9.
78. Kim SH, Shin KJ, Kim D, et al. Luteolin inhibits the nuclear factor-kappa B transcriptional activity in Rat-1 fibroblasts. Biochem Pharmacol. 2003 Sep 15;66(6):955-63.
79. Das M, Ram A, Ghosh B. Luteolin alleviates bronchoconstriction and airway hyperreactivity in ovalbumin sensitized mice. Inflamm Res. 2003 Mar;52(3):101-6.
80. Yi L, Li Z, Yuan K, et al. Small molecules blocking the entry of severe acute respiratory syndrome coronavirus into host cells. J Virol. 2004 Oct;78(20):11334-9.
81. Bae SC, Kim SJ, Sung MK. Inadequate antioxidant nutrient intake and altered plasma antioxidant status of rheumatoid arthritis patients. J Am Coll Nutr. 2003 Aug;22(4):311- 5.
82. Maier CM, Chan PH. Role of superoxide dismutases in oxidative damage and neurodegenerative disorders. Neuroscientist. 2002 Aug;8(4):323-34.
83. Fattman CL, Schaefer LM, Oury TD. Extracellular superoxide dismutase in biology and medicine. Free Radic Biol Med. 2003 Aug 1;35(3):236-56.
84. Chung JM. The role of reactive oxygen species (ROS) in persistent pain. Mol Interv. 2004 Oct;4(5):248-50.
85. Flohe L. Superoxide dismutase for therapeu- tic use: clinical experience, dead ends and hopes. Mol Cell Biochem. 1988 Dec;84(2):123-31.
86. Marsili V, Calzuola I, Gianfranceschi GL. Nutritional relevance of wheat sprouts containing high levels of organic phosphates and antioxidant compounds. J Clin Gastroenterol. 2004 Jul;38(6 Suppl):S123-6.
87. Calzuola I, Marsili V, Gianfranceschi GL. Synthesis of antioxidants in wheat sprouts. J Agric Food Chem. 2004 Aug 11;52(16):5201-6.
88. Peryt B, Szymczyk T, Lesca P. Mechanism of antimutagenicity of wheat sprout extracts. Mutat Res. 1992 Oct;269(2):201-15.
89. Peryt B, Miloszewska J, Tudek B, Zielenska M, Szymczyk T. Antimutagenic effects of sev- eral subfractions of extract from wheat sprout toward benzo[a]pyrene-induced mutagenicity in strain TA98 of Salmonella typhimurium. Mutat Res. 1988 Oct;206(2):221-5.
90. Burchett KM. SAS Release 32.3 at the University of Hawaii (01335001) by Environmental Health Associates.