vitality at every stage in life - american academy of...
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Vitality at Every Stage in Life
Restoring Testosterone Testosterone Balance
James B. LaValle RPh,CCN, DHM, DHPh Metabolic Code® Nutri1on CEO, Integra?ve Health Resources
§ Copyright © 2013 James B. LaValle, Integrative Health Resources, LLC. All rights reserved. No part of this material may be used or reproduced in any manner whatsoever, stored in a retrieval system, or transmitted in any form, or by any means, electronic, mechanical, photocopying, recording or otherwise, without prior permission of the author.������This material is provided for educational and informational purposes only to licensed health care professionals. This information is obtained from sources believed to be reliable, but its accuracy cannot be guaranteed. Herbs and other natural substances are very powerful and can occasionally cause dangerous allergic reactions in a small percentage of the population. Licensed health care professionals should rely on sound professional judgment when recommending herbs and natural medicines to specific individuals. Individual use of herbs and natural medicines should be supervised by an appropriate health care professional. The use of any specific product should always be in accordance with the manufacturer's directions.���
Testosterone
§ Androgenic hormone; 10x more prevalent in men than women
§ Declining testosterone levels and testosterone/cor?sol ra?o common in aging and increased stress
§ Low levels of T reported in approximately 38.7% of men over 45
Mulligan T, Frick MF, Zuraw QC, Stemhagen A, McWhirter C. Prevalence of hypogonadism in males aged at least 45 years: the HIM study. Int J Clin Pract. 2006;60:762-‐9.
Testosterone
§ Declines in men and women can lead to: – Weight gain – Insulin signaling problems, Type 2 diabetes – Chronic inflamma?on – Decreased libido/erec?le dysfunc?on – Thyroid imbalances – Cardiovascular problems – Muscle loss – Memory loss and cogni?ve decline – Sleep problems – Increased risk of osteoporosis – All cause mortality in men
Potential Factors in Low Testosterone: – Deficiency of nutrients i.e. zinc, vitamin D
– Stress -‐ elevated cor?sol produc?on and reduced DHEA
– Overtraining – Gonadal Trauma – Head Trauma – Environmental Intoxica?on from Xeno-‐estrogens – Visceral Fat
Testosterone
§ 2013 study 809 men
§ Testosterone and SHBG (serum hormone binding globulin) levels correlated with biomarkers of inflamma?on including CRP (C-‐reac?ve protein)
§ Conclusion: – In men, higher testosterone to estrogen levels can lead to decreased CRP and an?-‐inflammatory effects
Tsilidis et al. Associa?on between endogenous sex steroid hormones and inflammatory biomarkers in US men. Andrology. 2013.
Testosterone
§ Measurements immediately and 5 min post-‐exercise show an age-‐dependent increase in T levels
§ Intense training/over-‐training reported to decrease testosterone levels – Also increases cor?sol levels and oxida?ve stress Kraemer et al. Hormonal Responses and Adapta?ons to Resistance Exercise and Training. Sports Medicine. 2005;35(4):339-‐361.
The Stress Factor
§ As inflammation or stress goes up, cortisol goes up § Increased cortisol blocks T4 conversion to T3 which causes
TRH to be up regulated to create more T4 § Increasing TRH will increase prolactin which in turn § Down regulates LH and FSH production which § Down regulates testosterone § As testosterone goes down, so does growth hormone
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Insulin Cortisol/DHEA
Testosterone
To Make Matters Worse: Multiple Hormonal Shifts
• Cortisol mobilizes glycogen from liver • Cortisol decreases insulin sensitivity • Cortisol increases TNF alpha directly
• Cortisol:Testosterone ratio • Catabolic/Anabolic Balance
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Bottom Line:
§ Higher testosterone to cor?sol ra?os are correlated to strength gains and ?ssue anabolism and improved performance and overall well-‐being in men and women
Testosterone Levels § Testosterone < 250 ng/dl is consistent with
health risk. Optimal is 500 to 700 § Always get a “morning” specimen § Assess FREE testosterone using the Carruthers
Nomogram. – 70 to 100 is borderline - Tx if symptomatic – <70 is abnormal
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Restosterone § Formulated to helps support testosterone balance in men and women
§ Helps balance cor?sol levels to improve testosterone/cor?sol ra?o
§ Helps maintain metabolic balance and improved body composi?on
Restosterone
§ 2 capsules contain: – Eurycoma (Eurycoma longifolia) root 200mg
– 50:1 (w/w) extract
– Zinc (as zinc mono-‐l-‐methionine) 25 mg
– Phosphatidylserine 200 mg
Eurycoma (Eurycoma longifolia) root § Tongkat ali or “Malaysian ginseng” -‐ used in
SE Asian cultures for improved testosterone levels, libido
§ Reported to improve testosterone levels (free and total) in men and women
§ Also improves testosterone/cor?sol ra?o
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Eurycoma (Eurycoma longifolia) root § Quassinoids - major phytochemical compounds
§ Laboratory studies: – Aromatase inhibition – At high concentration may also have phosphodiesterase
inhibiting properties
§ Helps stimulate osteoblast proliferation and osteoclast apoptosis
Eurycoma (Eurycoma longifolia) root § 2013 study (n=25; 13 men, 12 women; ages 52-72)
§ 400mg standardized water extract of Eurycoma QD x 5 weeks
§ Significant increases in total and free testosterone
§ Significant declines in SHBG
§ Improved muscular force Henkel RR, Wang R, Bassett SH, et al. Tongkat ali as a potential herbal supplement for physically active male and female seniors-A pilot study. Phytother Res. 2013;[Epub ahead of print].
Eurycoma (Eurycoma longifolia) root § 2013 clinical trial § N=63 men and women § 200 mg QD standardized water extract for 4 weeks § 37 % decrease in cor?sol levels § 16% increase in testosterone levels § Reduced symptoms:
– -‐11% stress – -‐15% confusion – -‐12% anger
Talbom SM, Talbom JA, George A, et al. Effect of Tongkat Ali on stress hormones and psychological mood state in moderately stressed subjects. J Int Soc Sports Nutr. 2013;10(1):28.
Eurycoma (Eurycoma longifolia) root § 2012 randomized, double-‐blind, placebo controlled parallel
group study (n=109 men; ages 30-‐55)
§ 300 mg QD Eurycoma root standardized water extract for 12 weeks
§ Reported improvements in erec?on, sexual libido, sperm mo?lity and semen volume
§ A significant improvement in fat mass was also reported in subjects with a BMI > 25.
Ismail SB, Wan Mohammad WM, George A, et al. Randomized Clinical Trial on the Use of Physta Freeze-‐dried Water Extract of Eurycoma longifolia for the Improvemetn of Quality of Life and Sexual Well-‐Being in Men. Evid Based Complement Alternat Med. 2012;2012:429268.
Zinc § Necessary for the func?oning of over 300 different
enzymes § Plays a vital role in a balanced metabolism § An?oxidant/Immune balance § Prostate epithelial cells contain high amounts of zinc § Helps maintain testosterone balance § Laboratory studies report zinc has 5 alpha-‐reductase and
aromatase ac?vity
Zinc § Na?onal Health and Nutri?on Examina?on Survey,
1988-‐94, adults 60 years and older
§ Analyzed in 2002 for dietary intake
§ Reported prevelance of dietary zinc intake was low in those over 60 years (males, 35-‐41%; females, 36-‐45%)
Ervin et al. Mineral intakes of elderly adult supplement and non-supplement users in the third national health and nutrition examination survey. J Nutr. 2002;132(11):3422-7.
Zinc
§ Zinc Deficiency directly effects T levels § Zinc acts as an aromatase inhibitor low zinc=high estrogen
§ Low iron and zinc go hand in hand so check Fe zinc status and serum testosterone levels of healthy adults, ferri?n pool and iron if you have trained hard
Prasad AS, Mantzoros CS, Beck FW, Hess JW, Brewer G; Jhmp://www.ncbi.nlm.nih.gov/pubmed/8875519#Milanov, S., E. Maleeva, M. Tashkov. Tribestan effect on the concentra?on of some hormones in the serum of healthy subjects (1981)
Zinc § Clinical study (n=40, aged 20-‐80 yrs) § 4 of younger men placed on zinc restric?on for 20 weeks § Others were marginally zinc-‐deficient normal elderly men
place on zinc supplementa?on for six months § Zinc restric?on was associated with a significant decrease
in serum testosterone concentra?ons § Zinc supplementa?on resulted in significant increases in
serum testosterone – Prasad et al, Zinc status and serum testosterone levels of healthy adults. Nutri?on. 1996;12(5):
344-‐8
Zinc § Some drugs can deplete Zince from the body, including:
– ACE Inhibitors – Clofibrate – Cor?costeroids – H2 Antagonists (Tagamet, Zantac, Pepcid, Axid) – Iron/Copper as nutrient replenishment – Loop Diure?cs (including Lasix/furosemide) – Oral Contracep?ves – PPIs (proton pump inhibitors, including Prilosec) – Tetracycline an?bio?cs – Thiazide Diure?cs (including hydrochlorothiazide) – Valproic Acid – Zidovudine
LaValle JB, Pelton R, Hawkins EB, et al. Drug Induced Nutrient Deple5on, 2nd ed. LexiComp:Hudson, OH;2001:498-‐511.
Phosphatidylserine
§ Phospholipid found in cell membranes
§ An?oxidant
§ Associated with improving brain and neurological func?on
§ Also reported to help balance testosterone to cor?sol ra?o in response to stressors
Phosphatidylserine
§ 2006 study in male cyclists
§ 750 mg PS QD for 10 days
§ PS significantly improved exercise time to exhaustion at 85% VO2max
Kingsley et al. Effects of phosphatidylserine on exercise capacity during cycling in active males. Med Sci Sports Exerc. 2006;38(1):64-71.
Phosphatidylserine § 10 healthy males § DB cross-over placebo controlled § 15 minute ergometer test at 65-85% VO2max § Compared to placebo, PS improved AUC for testosterone/
cortisol ratio
§ Conclusion: “These findings suggest PS is an effective supplement for combing exercise-induced stress and preventing the physiological deterioration that can accompany too much exercise. PS supplementation promotes a desired hormonal status for athletes by blunting increases in cortisol levels.”
Starks et al The effect of phosphaJdylserine on endocrine response to moderate intensity exercise. J Int Sports Nutr.2008;5:11.
Reward Reward Imbalances, Cravings and Weight Control James B. LaValle R.Ph.,CCN, DHM, DHPh Metabolic Code® Nutri1on CEO, Integra?ve Health Resources
Reward Cascade
§ Low serotonin and dopamine = Imbalances in Reward Cascade
§ Imbalances lead to weight gain
§ Increased cravings/addic?ons
Schweighofer N, Bertin M, Shishida K, et al. Low-serotonin levels increase delayed reward discounting in humans. J Neurosci. 2008 Apr 23;28(17):4528-32. Erratum in: J Neurosci. 2008 May 21;28(21):5619.
Dopamine and Reward § Gene?c predisposi?on lends toward addic?on
behavior
§ Studies report obesity associated with decreased number of dopamine D2 receptors
§ The higher the BMI, the lower # of receptors
S?ce E, Spoor S, Ng J, Zald DH. Rela?on of obesity to consummatory and an?cipatory food reward. Physiol Behav. 2009 Jul 14;97(5):551-‐60. Epub 2009 Mar 27. Review.
Barnard ND, Noble EP, Ritchie T, et al. D2 Dopamine receptor Tag1A polymorphism, body weight and dietary intake in type 2 diabetes..Nutri?on. 2009 Jan;25(1):58-‐65.
Dopamine and Reward § Hyperinsulinemia also interferes with
dopamine clearance
§ Leads to imbalances in mesolimbic dopaminergic reward circuitry
§ Leads to reward-‐cascade imbalance and sa?ety dysfunc?on
S?ce E, Spoor S, Ng J, Zald DH. Rela?on of obesity to consummatory and an?cipatory food reward. Physiol Behav. 2009 Jul 14;97(5):551-‐60. Epub 2009 Mar 27. Review.
Barnard ND, Noble EP, Ritchie T, et al. D2 Dopamine receptor Tag1A polymorphism, body weight and dietary intake in type 2 diabetes..Nutri?on. 2009 Jan;25(1):58-‐65.
Reward § Helps support dopamine and serotonin pools
§ Helps balance the reward cascade system
§ Helps improve blood glucose regula?on
§ Helps support fat u?liza?on and storage
§ Helps support thyroid hormone balance
§ Decreased cravings
Reward § 2 capsules contains:
– Mucuna (Mucuna pruriens) seed 150 mg Standardized to 95% L-Dopa – L-Tyrosine 200 mg – Evodia (Evodia rutaecarpa) fruit 40 mg Standardized to 98% evodiamine
– Green tea (Camellia sinensis) leaf 400 mg Standardized to 50% ECGC
– Guarana (Paullinia cupana) seed 200 mg Standardized to 22% caffeine
– Quatrefolate 1 mg
Mucuna (Mucuna pruriens) seed § Velvet bean – indigenous to tropical
regions in Africa, India, South America and the West Indies
§ Contains L-‐Dopa
§ L-‐Dopa drug therapy for Parkinson’s leads to dyskinesia in majority of pa?ents
§ Mucuna is reported to produce a very low incidence of dyskinesia
Lieu et al. A water extract of Mucuna pruriens provides long-‐term ameliora?on of parkinsonism with reduced risk for dykinesias. Parkinsonism Relat Disord. 2010;16(7):458-‐65.
Mucuna
§ Lab and Human studies: – An?oxidant – Improves dopamine pools – Neuroprotec?ve – An?parkinsonian
Manyam BV, Dhanasekaran M, Hare TA. Neuroprotec?ve effects of the an?parkinson drug Mucuna pruriens. Phytother Res. 2004 Sep;18(9):706-‐12. Katzenschlager R, Evans A, Manson A, et al. Mucuna pruriens in Parkinson's disease: a double-‐blind clinical and pharmacological study. J Neurol Neurosurg Psychiatry. 2004 Dec;75(12):1672-‐7.
Mucuna
§ Increased dopamine important in: – Behavior/mood – Cogni?on/amen?on – Voluntary movement – Supports reward cascade -‐ mo?va?on and reward – Reduces craving pamerns – Inhibi?on of prolac?n – Sleep regula?on
L-Tyrosine
§ Non-‐essen?al amino acid
§ Precursor for catecholamines (dopamine, norepinephrine, epinephrine)
§ Combines with iodine and forms thyroxine (T4)
§ Helps improve thermogenesis
§ Helps support dopamine pools Lehnert H, et al. Neurochemical and behavioral consequences of acute, uncontrollable stress: effects of dietary
tyrosine. Brain Res. Jun1984;303(2):215-‐23.
Evodia (Evodia rutaecarpa) fruit
§ Standardized to 98% evodiamin
§ Traditional medicine in Asian cultures for blood sugar, thermogenic/weight control properties
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Evodia
Lab studies:
§ Stimulates tryptophan hydroxylase 2 (THP2)
§ Converts tryptophan to 5-HTP
§ ↑ serotonin pools
Wang Y, et al. [Regulatory effects of Wuzhuyutang (Evodiae prescription) and its consisting herbs on TPH2 promoter]. Zhongguo Zhong Yao Za Zhi. 2009;34(17):2261-4.
Evodia
Lab studies:
§ Anti-inflammatory – COX-2
§ Helps improve insulin sensitivity
Ko HC, Wang YH, Liou KT, et al. An?-‐inflammatory effects and mechanisms of the ethanol extract of Evodia rutaecarpa and its bioac?ve components on neutrophils and microglial cells. Eur J Pharmacol. 2007 Jan 26;555(2-‐3):211-‐7. Epub 2006 Oct 17.
§ ↑ Adap?ve stress response
§ Lipoly?c
§ Inhibits adipogenesis via the EGFR-‐PKC alpha-‐ERK signaling pathway
§ Binds to vanilloid receptor TRPV1 (capsaicin receptor)
Moon TC, et al. A new class of COX-‐2 inhibitor, rutaecarpine from Evodia rutaecarpa. Inflamm Res 1999; 48: 621-‐5. Wang T, et al. Evodiamine inhibits adipogenesis via the EGFR-‐PKCalpha-‐ERK signaling pathway.
FEBS Lem. 2009 Nov 19;583(22):3655-‐9. Epub 2009 Oct 23.
Kobayashi Y, et al. Capsaicin-‐like an?-‐obese ac?vi?es of evodiamine from fruits of
Evodia rutaecarpa, a vanilloid receptor agonist. Planta Med. 2001 Oct;67(7):628-‐33.
Evodia
Evodia (Evodia rutaecarpa)
§ ↑ Uncoupling protein-1 (UCP1)
§ Improves insulin sensitivity
§ ↑Gastric motility Moon TC, et al. A new class of COX-2 inhibitor, rutaecarpine from Evodia rutaecarpa. Inflamm Res 1999; 48: 621-5. Wang T, et al. Evodiamine inhibits adipogenesis via the EGFR-PKCalpha-ERK signaling pathway. FEBS Lett. 2009 Nov 19;583(22):
3655-9. Epub 2009 Oct 23.
Adaptive Stress
Evodia
§ Clinical study in 125 obese women
§ Improved weight loss and BMI after evodia and diet changes over placebo
Kim H, et al. Effect of Herbal Ephedra sinica and Evodia rutaecarpa on Body Composition and Resting Metabolic Rate: A Randomized, Double-blind Clinical Trial in Korean Premenopausal Women. Journal of Acupuncture and Meridian Studies. 2008;1(2):128-138.
Green Tea (Camellia Sinensis) leaf
� Standardized to 50% (-)epigallocatechin-3-gallate (EGCG) � Antioxidant
– Up to 20 times more potent than vitamin E in reduction of peroxides
� Reported to help improve immunity, performance and endurance, mental clarity and fat metabolism
� Lab studies report decreased muscle inflammation and improved recovery times in exercise
Haramizu S, et al. Catechins suppress muscle inflammation and hasten performance recovery after exercise. Med Sci Sports Exerc. 2013;45(9):1694-702.
Green Tea
§ 35 males dbl blnd placebo controlled § Dose 640mg/day polyphenols § 4 wks supplementa?on with strength training
§ Hydroxyperoxides at 4 wk in P group § Crea?ne Kinase elevated in P group § Jaroslaw Sacharuk, Bozena Balasinska et al, Green Tea extract gives protec?on against
exercise induced oxida?ve damage in healthy men Nutri?on Research Volume 31 Issue 11 Pages 813-‐821, November 2011
Green Tea
§ Green Tea increases famy acid oxida?on during exercise
§ Average oxida?on rate 17% higher § 13% increase in insulin sensi?vity § Contribu?on of famy acid expenditure on 30 minute cycle ride at 60% max (12 Male)
§ Improved insulin sensi?vity and glucose tolerance
§ Venables, Michelle, Hulston, Carl J, et al: Green tea extract inges?on , fat oxida?on, and glucose tolerance in healthy humans Am J Clin Nutr March 2008 vol.87 no.3 778-‐784
§ Helps promote weight loss
§ Increases thermogenesis
§ Fat ?ssue oxida?on increased – PPAR driven
§ Used in many weight loss supplements (caffeine and aspirin also added many ?mes for synergis?c thermogenic proper?es).
Green Tea
Shixian Q, et al. Green tea extract thermogenesis-‐induced weight loss by epigallocatechin gallate inhibi?on of catechol-‐o-‐methyltransferase. J Med Food. 2006;9(4):451-‐8. Boschmann M, Thielecke F. The effects of epigallocatechin-‐3-‐gallate on thermogenesis and fat oxida?on in obese men: a pilot study. J Am Coll Nutr. 2007 Aug;26(4):389S-‐395S.
§ 2010 Meta analysis (15 studies, n=1,243)
§ Green tea had clinically significant reduc?ons in anthropometric variables
– BMI (-‐.55) – Body weight (-‐1.38 kg) – Waist circumference (-‐1.93 cm)
Phung et al. Effect of green tea catechins with or without caffeine on anthropometric measures: a systema?c review and meta-‐analysis. Am J Clin Nutr. 2010;91(1):73-‐81.
Green Tea
Guarana (Paullinia cupana) seed
§ Contains high amounts of caffeine – Some theophylline and theobromine
§ CNS s?mulant § Caffeine reported to be ergogenic § Clinical Studies -‐ Improves endurance and performance
Hodgson AB, et al. The metabolic and performance effects of caffeine compared to coffee during endurance exercise. PLoS One. 2013;8(4):e59561. Desbrow B, Biddulph C, Devlin B, Grant GD, Anoopkumar-‐Dukie S, et al. (2012) The effects of different doses of caffeine on endurance cycling ?me trial performance. Journal of sports sciences 30: 115–120. Jenkins NT, et al. Ergogenic effects of low doses of caffeine on cycling performance. Int J Sport Nutr Exerc Metab. 2008;18:328–342.
Guarana - Caffeine § 2004 Meta analysis § 40 double-‐blind, placebo-‐controlled studies reviewed
§ Effects of caffeine on exercise performance § Caffeine improves exercise tes?ng by 12.3% § Endurance exercise significantly improved vs. placebo
§ Decreased ?me to exhaus?on Doherty M, Smith PM. Effects of caffeine inges?on on exercise tes?ng: a meta-‐analysis. Int J Sport Nutr Exerc Metab. 2004;14(6):626-‐46.
Guarana - Caffeine § 2010 Meta analysis § 15 double-‐blind, placebo-‐controlled studies reviewed (n=1,243)
§ Effects of caffeine combined with green tea for weight loss
§ Sta?s?cally significant reduc?ons in BMI and waist circumference over green tea alone
Phung OJ, Baker WL, Mamhews LJ, et al. Effect of green tea catechins with or without caffeine on anthropometric measures: a systemic review and meta-‐analysis. Am J Clin Nutr. 2010;91(1):73-‐81.
Quatrefolate
§ 5-‐methyltetrahydrofolate § “ac?ve” form of folic acid, complexed with glucosamine for improved absorp?on and bioavailability
§ Improved methyla?on and decreased homocysteine forma?on
§ Reported to help improve neurochemical balance McCully KS. Homocysteine, vitamins, and vascular disease preven?on. Am J Clin Nutr. 2007;86(5):1563S-‐8S.
Quatrefolate § 2013 clinical study (n=14 high-‐performance handball players)
§ Subjects given 200mcg folic acid daily x 2 months, then no folic acid x 2 months
§ Significant increases in homocysteine correlate with decreased training ?me
§ Nega?ve correla?on in serum Hcy and supplemental folic acid reported
§ Authors concluded: – “Folic acid supplementa?on may protect athletes against altera?ons
that can lead to cardiovascular events related to exer?on during compe??on.”
Molina-‐Lopez J, et al. Effect of folic acid supplementa?on on homocysteine concentra?on and associa?on with training in handball players. J Int Sco Sports Nutr. 2013;10(1):10.