Herbs and Nutrients for Healthy Aging

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Herbs and Nutrients for Healthy Aging Kerry Bone Co-Founder and Director Research and Development MediHerb Adjunct Associate Professor, University of New England, Australia

Key Herbs and Nutrients Japanese Knot Weed (Polygonum cuspidatum) St Mary s Thistle Korean Ginseng Ginkgo Green Tea Garlic Omega-3 fatty acids Folate, B12 Echinacea 2

Healthy Aging - Key Products HerbaVital Vitanox Garlic 5000mg Folic Acid B 12 Echinacea Premium Tuna Omega-3 Oil 3

Resveratrol as a CR Mimetic CR is not practical, so the search is on for other ways to activate the SIRT pathway Resveratrol has emerged as an important lead Resveratrol given to overfed middle-aged mice countered many of the adverse changes in metabolic pathways and improved survival These dramatic results provided worldwide attention and the observation that you can eat your cake and not have it Baur JA, Pearson KJ, Price NL et al. Nature 2006; 444(7117): 337-342 4

Resveratrol and Healthy Aging A PubMed search in March 2011 identified 3900+ publications on resveratrol. In contrast there are only around half this number on CR Resveratrol demonstrates an amazing array of health benefits 5

How Much Resveratrol? One bottle of red wine contains just 2 to 3 mg The human equivalent of the resveratrol dose used in the Nature mice study was around 140 mg/day 1 1 Reagan-Shaw S, Nihal M, Ahmad N. FASEB J 2008; 22(3): 659-661 6

How Much Resveratrol? A recent clinical trial in 19 overweight/obese men and women examined resveratrol s impact on endothelial function and cardiovascular health at doses of 30, 90 and 270 mg/day Resveratrol showed significant benefit, but there was only a small additional benefit between the 90 and 270 mg dose 1 1 Wong RHX, Howe PRC, Buckley JD et al. Acute resveratrol supplementation improves flow-mediated dilatation in overweight/obese individuals with mildly elevated blood pressure. Nutr Metab Cardiovasc Dis 2010; [Epub ahead of print] 7

Other Phytochemical SIRT1 Activators While the intense focus has been on resveratrol, other phytochemicals have been shown to activate SIRT1 or the SIRT1 pathway in various in vitro models Silymarin and its components are active in protecting cells from various stressors by activating SIRT1 pathways 1,2 1 Li LH, Wu LJ, Tashiro SI et al. Activation of the SIRT1 pathway and modulation of the cell cycle were involved in silymarin's protection against UV-induced A375-S2 cell apoptosis. J Asian Nat Prod Res 2007; 9(3-5): 245-252 2 Zhou B, Wu LJ, Li LH et al. Silibinin protects against isoproterenol-induced rat cardiac myocyte injury through mitochondrial pathway after upregulation of SIRT1. J Pharmacol Sci 2006; 102(4): 387-395 8

Silymarin and Insulin Support A recent placebo-controlled clinical trial assessed the effects of Silymarin extract (200 mg TDS) for 4 months The trial reported on blood glucose and cholesterol levels in the study subjects Huseini H, et al. The efficacy of Silybum marianum (L.) Gaertn. (silymarin) in the treatment of type II diabetes: a randomized, doubleblind, placebo-controlled, clinical trial. Phytother Res 2006; 20(12): 1036-1039 9

Korean Ginseng & Insulin Support Korean Ginseng caused no change in HbA 1C or fasting plasma glucose in a placebo-controlled clinical trial However, normal fasting plasma insulin was significantly supported for Korean Ginseng (by 34%) whereas it increased in the placebo group (by 10%) Vuksan V, Sung MK, Sievenpiper JL, et al. Korean red ginseng (Panax ginseng) improves glucose and insulin regulation in well-controlled, type 2 diabetes: results of a randomized, double-blind, placebocontrolled study of efficacy and safety. Nutr Metab Cardiovasc Dis 2008; 18(1): 46-56 10

Korean Ginseng and Good Health Health promoting effects have been demonstrated in numerous pharmacological studies for whole root extracts and various components of Korean Ginseng 1 Korean epidemiological studies have found improved health rates (50%) in Ginseng users 1 The protective effect increased with rising duration and frequency of Ginseng intake 1 1 Mills S, Bone K. Principles and Practice of Phytotherapy: Modern Herbal Medicine. Churchill Livingstone, Edinburgh, 2000, p 428 11

Adaptogens and DHEA After oral administration of 6 g of Korean Red Ginseng for 30 days to postmenopausal women, DHEAS was increased by around 13% Tode T, Kikuchi Y, Hirata J et al. Effect of Korean red ginseng on psychological functions in patients with severe climacteric syndromes. Int J Gynaecol Obstet 1999; 67(3): 169-174 12

Adaptogens and DHEA Ashwaganda (Withania somnifera) significantly increased DHEAS by 30% in a placebo-controlled clinical trial (p<0.001) Auddy B, Hazra J, Mitra A et al. A Standardized Withania Somnifera Extract Significantly Reduces Stress-Related Parameters in Chronically Stressed Humans: A Double-Blind, Randomized, Placebo- Controlled Study. J Am Nutra Assoc 2008; 11(1): 50-56 13

Ginkgo, Longevity and Good Health In investigating whether Ginkgo might help prevent support cognitive function, it was found that regular users of the extract had a significantly improved health outcomes in old age 1 Perhaps related to this, regular use of Ginkgo was also linked to improved ovarian health 1 Dartigues JF, Carcaillon L, Helmer C et al. Vasodilators and nootropics as predictors of dementia and mortality in the PAQUID cohort. J Am Geriatr Soc 2007; 55(3): 395-399 2 Ye B, Aponte M, Dai Y et al. Ginkgo biloba and ovarian cancer prevention: epidemiological and biological evidence. Cancer Lett 2007; 251(1): 43-52 14

Ginkgo Supports DNA In an uncontrolled trial conducted in 1995, Ginkgo extract supported DNA in Chernobyl workers 1 More recently the same dose of extract (120mg/day) supported DNA in patients needing thyroid support 2 This was in a more solid randomized, controlled clinical trial, so the evidence for benefit is quite good 1 Emerit I, Oganesian N, Sarkisian T et al. Radiat Res 1995; 144(2): 198-205 2 Dardano A, Ballardin M, Ferdeghini M et al. J Clin Endocrinol Metab 2007; 92(11): 4286-4289 15

Ginkgo and CV Health Ginkgo extract, 240 mg/day, for 2 months The effect of Ginkgo on quantity amounted to 11.9% (p<0.008) and size was reduced by 24.4% (p<0.023) More significantly, the Ginkgo treatment had beneficial effects on lipids Superoxide dismutase (SOD) was increased and oxidized LDL was significantly lowered Rodríguez M, Ringstad L, Schäfer P et al. Reduction of atherosclerotic nanoplaque formation and size by Ginkgo biloba (EGb 761) in cardiovascular high-risk patients. Atherosclerosis 2007; 192(2): 438-444 16

alliin alliinase allicin Important points: Need enteric-coating because enzyme is inactivated by stomach acid Need to test enzyme activity in every batch 17

Is Garlic Nature s Most Powerful Antioxidant? Thirteen elderly volunteers in Turkey were advised to take Garlic in their diet at a daily dose of 0.1 g/kg of body weight (7 g/day for a person weighing 70 kg) for 1 month 1 Before and after this period, fasting blood samples were taken to check the effect on antioxidant measures in red blood cells and plasma 1 Avci A, Atli T, Erguder IB et al. Effects of Garlic consumption on plasma and erythrocyte antioxidant parameters in elderly subjects. Gerontology 2008; 54(3): 173-176 18

Is Garlic Nature s Most Powerful Antioxidant? Garlic significantly lowered plasma and red blood cell malondialdehyde (MDA) levels and increased the activities of key antioxidant enzymes such as the all-important superoxide dismutase, which was increased by about 25% MDA measures the amount of oxidation of your body fats, quite literally how rancid you are 19

Omega-3 Fatty Acids The omega-3 fatty acid index is now recommended by some cardiologists as an independent cardiovascular risk factor. 1 The evidence for DHA+EPA in supporting triglycerides is extremely robust 2 A meta-analysis found that fish oil supplementation was associated with a significant cardiac benefits 1 Harris WS. The omega-3 index: clinical utility for therapeutic intervention. Curr Cardiol Rep 2010; 12(6): 503-508 2 Mattar M, Obeid O. Fish oil and the management of hypertriglyceridemia. Nutr Health 2009; 20(1): 41-49 3 León H, Shibata MC, Sivakumaran S et al. Effect of fish oil on arrhythmias and mortality: systematic review. BMJ 2008; 337: a2931 20

Folate, B12 and Aging The OPTIMA group recently found that the homocysteine-supporting B vitamins (folic acid 0.8 mg/day, B12 0.5 mg/day and B6 20 mg/day) significantly supported the brain in a randomized, double blind placebo-controlled trial over 2 years 1 Reduced telomere length in lymphocytes has been associated with higher homocysteine and lower folate in older men 2,3 1 Smith AD, Smith SM, de Jager CA et al. PLoS One 2010; 5(9): e12244 2 Bull CF, O Callaghan NJ, Mayrhofer G et al. Rejuvenation Res 2009; 12(5): 341-349 3 Paul L, Cattaneo M, D Angelo A et al. J Nutr 2009; 139(7): 1273-1278 21

Echinacea and Immunosenescence One of the persistent controversies about Echinacea is whether it is safe to be taken consistently for long periods of time Mice were fed Echinacea purpurea root from 7 weeks of age to 13 months at equivalent normal human doses. 1 Long-term use of Echinacea was not only not detrimental, but distinctly beneficial 1 Brousseau M, Miller SC. Enhancement of natural killer cells and increased survival of aging mice fed daily Echinacea root extract from youth. Biogerontology 2005; 6(3): 157-163 22

Echinacea and Immunosenescence By 13 months of age, 46% of the control mice fed the standard chow were still alive compared to 74% of those consuming Echinacea The NK cell levels and function in the Echinaceafed mice were considerably elevated compared to controls In other words this and other studies by Miller found that Echinacea reverses the aging effects observed on innate immunity and prolongs lifespan in a meaningful manner Miller SC. Echinacea: a Miracle Herb against Aging and Cancer? Evidence In vivo in Mice. ecam 2005; 2(3): 309-314 23

Echinacea Root and HSPs Parameter Before After % Heat Shock Protein Males 2.69 4.36 62% Females 1.65 2.24 36% White Cell Count (x10 9 /L) Males 7.0 7.5 7% Females 6.2 7.0 13% Echinacea Premium was given at 2 tablets per day for 2 weeks in an open-label clinical trial Agnew LL, Guffogg SP, Matthias A, Bone KM et al. Echinacea intake induces an immune response through altered expression of leukocyte hsp70, increased white cell counts and improved erythrocyte antioxidant defences. J Clin Pharm Ther 2005; 30(4), 363-369

Key Products for Healthy Longevity HerbaVital tablets (2 to 4 per day) Vitanox tablets (1 to 2 per day) Garlic 5000mg tablets (1 to 2 per day) Folic Acid B 12 tablets (1 per day) Echinacea Premium tablets (2 to 3 per day) Tuna Omega-3 Oil capsules (2 to 4 per day) 25

HerbaVital Each tablet contains: Japanese Knot Weed root extract 100:1 from Polygonum cuspidatum root 8.0 g Containing resveratrol 36 mg Milk Thistle seed extract 70:1 from Silybum marianum seed 4.2 g Containing flavanolignans calc. as silybin 48 mg Korean Ginseng root extract 5:1 from Panax ginseng root 250 mg Containing ginsenosides calc. as Rg 1 and Rb 1 4.2 mg 80 mg 60 mg 50 mg 26

HerbaVital (continued) Masson Pine bark extract 100:1 from Pinus massoniana bark 5.0 g Containing proanthocyanidins 37.5 mg Ginkgo leaf extract 50:1 from Ginkgo biloba leaf 1.5 g Containing ginkgo flavonglycosides 7.2 mg Containing ginkgolides and bilobalide 1.8 mg 50 mg 30 mg Dosage: 2 to 4 tablets per day 27

Vitanox Each tablet contains: Rosemary leaf 5:1 extract from Rosmarinus officinalis leaf 1.0 g Green Tea 25:1 extract from Camellia sinensis leaf 4.2 g Containing catechins 83.35 mg Turmeric rhizome 25:1 extract from Curcuma longa rhizome 2.0 g Containing curcuminoids 70.4 mg 200 mg 166.7 mg 80 mg Grape seed 120:1 extract 50 mg from Vitis vinifera seed 6.0 g Containing procyanidins 42.5 mg 28 Dosage: 2 to 3 tablets per day

Garlic 5000mg Each tablet contains: Garlic bulb 6.5:1 extract from Allium sativum bulb 1.04 g Containing alliin 4.3 mg Garlic (Allium sativum) bulb powder Containing alliin 1.4 mg 160 mg 100 mg Dosage: 1 to 2 tablets per day The fresh weight of Garlic in each tablet is approximately 5.0 g, total alliin 5.7 mg 29

Echinacea Premium Each tablet contains: Echinacea root 4:1 extract from Echinacea angustifolia root 600 mg Containing alkylamides 2.0 mg Echinacea root 6:1 extract from Echinacea purpurea root 675 mg Containing alkylamides 2.1 mg 150 mg 112.5 mg Dosage: 1 tablet 2 to 3 times per day 30

Key Products for Healthy Longevity HerbaVital tablets (2 to 4 per day) Vitanox tablets (1 to 2 per day) Garlic 5000mg tablets (1 to 2 per day) Folic Acid B 12 tablets (1 per day) Echinacea Premium tablets (2 to 3 per day) Tuna Omega-3 Oil capsules (2 to 4 per day) 31