Natural Medicine Journal Men's Health Supplement: Vol 9 No 81 by Diversified Communications

AUGUST 2017 SUPPLEMENT

SPECIAL ISSUE

Menâ&#x20AC;&#x2122;s Health

Health Effects of Anger in Men The Link Between Erectile Dysfunction and Cardiovascular Disease

Natural Substance Enhances Exercise Performance Current Approaches to Urinary Incontinence

SPECIAL ISSUE MEN’S HEALTH AUGUST 2017 VOL 9, NO. 81 (SUPPL)

Contents

ABSTRACTS & COMMENTARY

Informed Prostate Cancer Patients Have Less Regret Following Treatment

Betalain-rich Concentrate Improves Exercise Performance

Adding L-Citrulline Increases Plasma L-Arginine in Men

PEER-REVIEWED ARTICLE

Health Effects of Anger in Men

AUDIO INTERVIEWS

26 Addressing Male Urinary Incontinence Interview with Ronald A. Morton, MD, FACS 28 Erectile Dysfunction’s Clues About Cardiovascular Health Interview with Daniel Chong, ND

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Contributors GEO ESPINOSA, ND, LAc, CNS, RH (AHG), is a renowned naturopathic and functional medicine doctor recognized as an authority in urology and men’s health. Espinosa is the founder and director of the Integrative and Functional Urology Center at New York University Langone Medical Center Geo Espinosa, ND, LAc, CNS, RH (NYULMC) and lectures internationally on the (AHG) application of integrative urology in clinical settings. He has been recognized as one of the top 10 Health Makers for Men’s Health by sharecare.com created by Dr. Mehmet Oz and WebMD. Espinosa is the author of the popular book Thrive, Don’t Only Survive: Dr. Geo’s Guide to Living Your Best Life Before & After Prostate Cancer. On his time off from work, he enjoys writing on his popular blog, DrGeo.com and spending time with his family.

KAROLYN A. GAZELLA has been writing and publishing integrative health information since 1992. She is the publisher of the Natural Medicine Journal and the author or coauthor of hundreds of articles and several booklets and books including her latest book The Definitive Guide to Thriving After Karolyn A. Gazella Cancer that she wrote with Lise Alschuler, ND, FABNO. Gazella is the co-creator and Chief Executive Officer of the iTHRIVE Plan, an innovative online wellness program specifically for cancer survivors.

TINA KACZOR, ND, FABNO, is editor in chief of Natural Medicine Journal and a naturopathic physician, board certified in naturopathic oncology. She received her naturopathic doctorate from National College of Natural Medicine, Portland, Oregon, and completed her residency in naturopathic Tina Kaczor, ND, oncology at Cancer Treatment Centers of FABNO America, Tulsa, Oklahoma. Kaczor received undergraduate degrees from the State University of New York at Buffalo. She is the past president and treasurer of the Oncology Association of Naturopathic Physicians and secretary of the American Board of Naturopathic Oncology. She has been published in several peer-reviewed journals. Kaczor is based in Eugene, Oregon.

MATT MUMBER, MD, is a board certified radiation oncologist with the Harbin Clinic in Rome, Georgia. He received his medical doctorate from the University of Virginia and he also did a fellowship in integrative medicine with the University of Arizona. He is the coauthor of the book Sustainable WellMatt Mumber, MD ness and the editor of the textbook Integrative Oncology: Principles and Practice. Mumber is the director of medical affairs of the iTHRIVE Plan.

STEVE RISSMAN, ND, a graduate of Bastyr University, is a tenured professor in the Department of Health Professions at Metropolitan State University of Denver, teaching in the integrative health program. His focus centers on the health of men and boys and he has therefore developed an area Steve Rissman, of concentration teaching men’s health, men ND across cultures, men and anger, and men in recovery. He is also the lead teacher of clinical pathophysiology. Rissman has a private practice at his farm office, north of Denver, working specifically as a mentor for men and boys. Rissman has studied, taught and worked in the field of men’s health for over 20 years. He has committed his naturopathic medical practice to improving the lives of men and boys by working with those suffering with anxiety, compulsive behaviors, anger issues, and lack of motivation or direction. Rissman utilizes both face-to-face counseling and online video consults to lead men/boys through the abyss of disease. JACOB SCHOR, ND, FABNO, is a graduate of National College of Naturopathic Medicine, Portland, Oregon, and now practices in Denver, Colorado. He served as president to the Colorado Association of Naturopathic Physicians and is on the board of directors of the Oncology Association of Jacob Schor, ND, Naturopathic Physicians. He is recognized FABNO as a fellow by the American Board of Naturopathic Oncology. He serves on the editorial board for the International Journal of Naturopathic Medicine, Naturopathic Doctor News and Review (NDNR), and Integrative Medicine: A Clinician’s Journal. In 2008, he was awarded the Vis Award by the American Association of Naturopathic Physicians. His writing appears regularly in NDNR, the Townsend Letter, and Natural Medicine Journal, where he is the Abstracts & Commentary editor.

EDITOR IN CHIEF Tina Kaczor, ND, FABNO

MESSAGE FROM THE PUBLISHER

ABSTRACTS & COMMENTARY EDITOR Jacob Schor, ND, FABNO

An Integrative Approach to Men’s Health

PUBLISHER Karolyn A. Gazella ASSOCIATE PUBLISHER Kathi Magee VP, CONTENT & COMMUNICATIONS Deirdre Shevlin Bell DESIGN Karen Sperry

According to the Centers for Disease Control and Prevention (CDC), in 2014 the leading causes of death in men were heart disease, cancer, stroke, diabetes, and Alzheimer’s disease. All of these conditions lend themselves well to an integrative approach to prevention and/or treatment. In this issue, we’ve touched on a broad array of men’s health topics. Our main peer-reviewed feature is on the health ramifications of anger in men. Steve Rissman, ND, takes us through the various types of men’s anger and describes how it affects the cardiovascular system, the immune system, pain, and erectile dysfunction. The paper shines a light on the unique role integrative practitioners can play in addressing this detrimental aspect of men’s health.

PUBLISHED BY IMPACT Health Media, Inc. Boulder, Colorado

In this issue, we’re also featuring two audio interviews with experts: one discussing the links between erectile dysfunction and cardiovascular disease, and the other focusing on male urinary incontinence.

Natural Medicine Journal (ISSN 2157-6769) is published 14 times per year by IMPACT Health Media, Inc. Copyright © 2017 by IMPACT Health Media, Inc. All rights reserved. No part of this publication may be reproduced in whole or in part without written permission from the publisher. The statements and opinions in the articles in this publication are the responsibility of the authors; IMPACT Health Media, Inc. assumes no liability for any information published herein. Advertisements in this publication do not indicate endorsement or approval of the products or services by the editors or authors of this publication. IMPACT Health Media, Inc. is not liable for any injury or harm to persons or property resulting from statements made or products or services referred to in the articles or advertisements.

In our Abstracts & Commentary, we delve into exercise performance, prostate cancer, and the combination of citrulline and arginine for men’s health. We hope you find the information in this special issue to be insightful and important to your work with your male patients. We have an exceptional team of writers, reviewers, and editors here at Natural Medicine Journal. I extend my deep appreciation to all those involved in this special issue, as well as those involved with the production of our monthly regular issue. If you are not getting our regular issue in your email box each month, click here to sign up for free. http://eepurl.com/d6zXb Thank you for all you do to keep the men of this world healthy! In good health,

Karolyn A. Gazella Publisher, Natural Medicine Journal

ABSTRACT & COMMENTARY

Informed Prostate Cancer Patients Have Less Regret Following Treatment Knowing about risks and side effects may improve quality of life REFERENCE

Hoffman RM, Lo M, Clark JA, et al. Treatment decision regret among long-term survivors of localized prostate cancer: results from the Prostate Cancer Outcomes Study. J Clin Oncol. 2017;35(20):2306-2314. DESIGN

Follow-up survey data gathered from a large, population-based cohort study known as the Prostate Cancer Outcomes Study originally published in the Journal of the National Cancer Institute.1 STUDY POPULATION

934 men treated in various US cities between October 1994 to 1995 who were part of a cohort who filled out baseline and 15-year surveys. They were diagnosed with localized prostate cancer, 59% classified as having low risk disease, diagnosed before the age of 75. Of the 934 total, 696 were treated with initial radical prostatectomy, 146 had initial radiation therapy, and 92 were treated with either watchful waiting (no treatment) or androgendeprivation therapy within 1 year of diagnosis. OUTCOMES MEASURED

Multivariable logistic regression analyses were used to identify factors associated with regret. A 15-year followup survey was used to determine several key factors including: • Demographics • Socioeconomic status • Treatment decision regret • Informed decision-making • General- and disease-specific quality of life • Health worry • PSA concern • Life outlook KEY FINDINGS

Survey response rate at the 15-year follow-up period was 69.3%. Most of the respondents had undergone radical prostatectomy, with 10.8% of the survey responses coming from those who were treated conservatively with watchful waiting or androgen-deprivation therapy. Overall, less than 15% expressed treatment decision regret with the highest amount (16.6%) of regret coming from those who underwent radiotherapy. Also, the men who were older and felt they made an informed treatment decision had the least amount of regret. The men who reported having symptoms with bowel function, sexual function, and greater PSA scores had the most regret.

Matt Mumber, MD

PRACTICE IMPLICATIONS Interestingly, these same researchers surveyed the same Prostate Cancer Outcomes Study participants 2 years after treatment so there is now 2 sets of data points to consider: 2-years (2003 study)2 and 15-years (2017 study). In the 2-year follow up, 2,365 men were evaluated and 59.2% were delighted or very pleased with their treatment choice. At the time of the 2-year follow-up, a large percentage of the men were cancer free (66.4%) and did not have urinary (64.2%), bowel (60.5%), or sexual dysfunction (65.9%) issues. In the second 15-year follow up study, a validated instrument to more accurately measure regret was added. This demonstrated that regret actually increased over time. In both studies, self-reported treatment regret was fairly low, which is good news. But that’s not the only interesting data that comes from this most recent study. This study, as well as previous research, demonstrates that regret is highly associated with lack of knowledge regarding adverse treatment affects such as bowel, urinary, and sexual dysfunction that may negatively impact quality of life after treatment.3,4 In related research, Davison et al found that men who assumed a more active role in their treatment decisions felt less regret.5 Hacking et al demonstrated that men who used a navigator to help with the treatment decision-making process had significantly less regret 6 months after treatment compared to those who did not use navigation.6 In this study, men who treated their cancer more conservatively with watchful waiting, which is also called active surveillance, and had normalized PSA without recurrence experienced the

“

Regret is highly associated with lack of knowledge regarding adverse treatment affects such as bowel, urinary, and sexual dysfunction that may negatively impact quality of life after treatment.

ABSTRACT & COMMENTARY

least amount of regret potentially due to lack of treatment side effects and quality of life issues. These researchers see this as an opportunity to promote comprehensive information about the active surveillance option to men with localized prostate cancer. The research does, in fact, demonstrate that active surveillance had similar outcomes and mortality when compared to initial radiotherapy and surgery. Due to lack of treatment side effects, active surveillance has emerged as a standard management option for men with very low and low risk prostate cancer.7,8 The researchers in this present study feel their findings “are timely for men with low-risk cancers who are being encouraged to consider active surveillance.” As a radiation oncologist, it is important for me to note that toxicities of treatment can vary over time. For example, this cohort was treated before the advent of Intensity Modulated Radiation (IMRT) which radically improved both short- and long-term side effect profiles of radiation therapy. Surgical advances have also occurred over time, such as robotic prostatectomy. Additionally, active surveillance as a discrete protocol did not exist formally in 1994-95. Regardless of these therapeutic improvements, it is important to realize that sometimes the conventional treatments we administer may cause long-term quality of life issues, such as urinary incontinence or sexual and bowel dysfunction. It’s also challenging to anticipate long-term effects that may not resolve. I work with patients to determine their risk tolerance, personal and psychological values, and other quality of life considerations to help them determine the right path. A correct path for a 50-year-old healthy man is likely different than the path for an unhealthy 78-year-old. We go over the options and discuss factors that are completely under their control—like how they eat, move their bodies, and manage their stress. We discuss that there is good data that these controllable factors can influence prostate cancer progression rates.9 The clinical take home message is that all men deserve to be well-informed about the complexities and nuances associated with each prostate cancer treatment option. Patients must be counseled to make decisions based on many factors, including treatment side effects, quality of life issues, recurrence risk, healthy lifestyle practices, and other aspects of care to ensure

the final decision is congruent with the patient’s values and expectations.10 When we help men diagnosed with prostate cancer look at their treatment options through this lens, we can reduce regret in both the short-term and long-term. REFERENCES 1

Potosky AL, Harlan LC, Gilliland FD, et al. Prostate cancer practice patterns and quality of life: the Prostate Cancer Outcomes Study. J Natl Cancer Inst. 1999;91(20): 1719-1724. 2 Hoffman RM, Hunt WC, Gilliland FD, et al. Patients satisfaction with treatment decisions for clinically localized prostate carcinoma. Results from the Prostate Cancer Outcomes Study. Cancer. 2003;97(7):1653-1662. 3 Kinsella J, Acher P, Ashfield A, et al: Demonstration of erectile management techniques to men scheduled for radical prostatectomy reduces long-term regret: A comparative cohort study. BJU Int. 2012;109:254-258. 4 Lin YH: Treatment decision regret and related factors following radical prostatectomy. Cancer Nurs. 2011;34:417-422. 5 Davison BJ, So AI, Goldenberg SL: Quality of life, sexual function and decisional regret at 1 year after surgical treatment for localized prostate cancer. BJU Int. 2007;100: 780-785. 6 Hacking B, Wallace L, Scott S, et al: Testingthe feasibility, acceptability and effectiveness of a ‘decision navigation’ intervention for early stage prostate cancer patients in Scotland—A randomized controlled trial. Psychooncology. 2013;22:1017-1024. 7 Hamdy FC, Lane JA, Mason M, et al. 10-year outcomes after monitoring, surgery, or radiotherapy for localized prostate cancer. N Engl J Med. 2016;375:1415-1424. 8 Tosoian JJ, Loeb S, Epstein JI, et al. Active surveillance of prostate cancer: Use, outcomes, imaging, and diagnostic tools. Am Soc Clin Oncol Educ Book. 2016;35:e235e245. 9 Ornish D, Weidner G, Fair WR, et al. Intensive lifestyle changes may affect the progression of prostate cancer. J Urol. 2005;174(3):1065-1069. 10 Fowler FJ Jr, Gallagher PM, Drake KM, et al. Decision dissonance: Evaluating an approach to measuring the quality of surgical decision making. Jt Comm J Qual Patient Saf. 2013;39:136-144.

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ABSTRACT & COMMENTARY

Betalain-rich Concentrate Improves Exercise Performance It’s not the nitrates in beets that enhance athletic performance REFERENCE

Montenegro CF, Kwong DA, Minow ZA, Davis BA, Lozada CF, Casazza GA. Betalain-rich concentrate supplementation improves exercise performance and recovery in competitive triathletes. Appl Physiol Nutr Metab. 2017;42(2):166-172. DESIGN

Participants were supplemented with a beetroot concentrate for 6 days and then completed 2 double-blind, crossover, randomized exercise timed trials that started 7 days apart. The exercise trials consisted of 40 minutes of cycling (75 ± 5% maximal oxygen consumption), followed by a timed 10-km run. Participants returned 24 hours later to complete a timed 5-km run to assess recovery. PARTICIPANTS

Twenty-two (9 men and 13 women) triathletes (age, 38 ± 11 years) recruited from the University of California at Davis area; all participants exercised more than 5 hours a week, had completed a triathlon within the past year, and were nonsmokers in good health. STUDY MEDICATION AND DOSAGE

For 6 days prior to each exercise trial, participants consumed either a betalain-rich concentrate (BRC) of beetroots (100 mg/d) or placebo. On the seventh day, participants received half their dose of BRC (50 mg) or placebo and then began a series of exercise trials 2 hours later. This beet concentrate was notable because it contained no sugars or nitrate. OUTCOME MEASURES

Time to complete the 10-km and 5-km runs; serum creatine kinase; heart rate; and perceived exertion. KEY FINDINGS

Participants ran the 10-km distance faster after taking the BRC than they did after taking placebo (49.5 ± 8.9 vs 50.8 ± 10.3 min; P=0.03). Despite running faster, their average heart rate and ratings of perceived exertion remained the same. Seventeen of the 22 participants ran the 5-km distance, which was run the day after the 10-km trial, faster after BRC (23.2 ± 4.4 vs 23.9 ± 4.7 min; P=0.003). Creatine kinase, a muscle damage marker, increased less (40.5 ± 22.5 vs 49.7 ± 21.5 U/L; P=0.02) from baseline after the 10-km run and subjective fatigue increased less (-0.05 ± 6.1 vs. 3.23 ± 6.1; P=0.05) from baseline to 24 hours after the 10-km run following BRC.

Jacob Schor, ND, FABNO

PRACTICE IMPLICATIONS In this study, beetroot improved 10-km run performance in competitive male and female triathletes. It also improved 5-km run performances 24 hours after the initial 10-km run, and the attenuated increase of creatine kinase and fatigue suggest an increase in recovery while taking beetroot. These findings support the use of beetroot for enhanced athletic performance. Gretchen Casazza, the principal author of this study, had another very similar study published barely 6 months earlier that suggested similar benefits from beetroot supplementation. In the earlier study, 13 competitive runners (all male) completed the same double crossover supplementation protocol but with a slightly different and easier exercise routine. After the same 6-day routine of 100 mg per day of BRC, participants spent 30 minutes on a treadmill and then completed a 5-km time trial. While exercising at the same intensity, the runners had a 3% lower heart rate, a 15% lower rate of perceived exertion (RPE), and a 14% lower blood lactate concentration after taking BRC, compared to the control (P=0.05). Also compared to the control, 10 of the 13 runners had faster times in the 5-km time trial (23.0±4.2 vs 23.6±4.0 min) with lower RPE (P<0.05) after taking BRC. Lactate dehydrogenase, a marker of muscle damage, increased less from baseline to immediately and 30 minutes after the 5-km time trial after beetroot treatment, despite no differences in subjective measures of muscle soreness and fatigue.1 Suffice it to say that beetroot extract seems to be helpful for athletic performance. Given the earlier papers (one of which has been reviewed in this journal) on beet extracts and athletic performance, these current data come as no surprise. The surprise is that up until now the assumed mechanism of action of beets, which are high in nitrate, was related to the rapid conversion of nitrate to nitric acid. The beneficial effect of beets was thought to be due to the effects of a surge in nitric acid, but the beet concentrates used in both of these Casazza studies were nitrate-free. We need another explanation as to why beets help athletes.

http://www.naturalmedicinejournal.com/journal/2014-02/beet-juice-physical-performance-enhancer

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ABSTRACT & COMMENTARY

Casazza suggests the benefit comes from betalains. The earlier of her 2 studies appears to be the first published that looked at betalains alone, without nitrates, and how they impact exercise performance. All prior studies had looked at beetroot juice that contained nitrates. Lansley’s 2011 study on competitive cyclists used juice that contained 6.2 mmol of nitrates,2 and Cermak’s 2012 study used juice with 8 mmol of nitrates.3 Again, because these 2 recent studies by Casazza used nitrate-free beet concentrate, we need to rethink our earlier assumptions.

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A new double-blind, randomized trial yields expected results: beet juice improves athletic performance. But the proposed mechanism of action? Unexpected.

”

Betalains, commonly used as food colorants, are the watersoluble pigments that give beets their vivid red color. Betalains have a wide range of biological activities with potential health benefits: they counter inflammation, protect the liver, and have anticancer and antioxidant activity.4 Betanin and betanidin, the main antioxidant components of betalains, inhibit lipid peroxidation and heme decomposition even at very low concentrations. Betalains are now considered a “new class” of dietary antioxidants.5 Studies show that pigments in betalains inhibit the growth of several different types of malignant tumors, including breast, liver, colon, and bladder cancers. Betalains fight cancer through effects on apoptosis—the process of programmed cell death built into all normal cells, but altered in cancer

cells. Other potential mechanisms of action include negative effects on genes that promote cancer cell survival and genes that control blood vessel growth. The anticancer activity of betalains is enhanced by this multipronged attack on cancer cell growth.6 Given the evidence that betalains have a wide range of healthy effects in the body, it makes sense that betalains might be the active component of beets responsible for improved exercise performance. In recent years, because of the nitric oxide theory, some have promoted beet juice extract as an herbal substitute for synthetic phosphodiesterase type 5 inhibitors such as sildenafil (aka Viagra). Research suggests that few if any herbs actually provide the promised chemical effects and that if these products have effect it is secondary to adulteration with active drugs.7 On the other hand, although we have yet to find publications on the subject, one might argue that the betalains alone, because they are potent antioxidants that lower reactive oxygen damage, may, like other plant polyphenols, protect against damage that leads to erectile dysfunction.8 REFERENCES 1 2 3 4

5 6 7 8

Van Hoorebeke JS, Trias CO, Davis BA, Lozada CF, Casazza GA. Betalain-rich concentrate supplementation improves exercise performance in competitive runners. Sports. 2016;4(3):40. Lansley KE, Winyard PG, Bailey SJ, et al. Acute dietary nitrate supplementation improves cycling time trial performance. Med Sci Sports Exerc. 2011;43(6):1125-1131. Cermak NM, Res P, Stinkens R, Lundberg JO, Gibala MJ, van Loon LJ. No improvement in endurance performance after a single dose of beetroot juice. Int J Sport Nutr Exerc Metab. 2012;22(6):470-478. Georgiev VG, Weber J, Kneschke EM, Denev PN, Bley T, Pavlov AI. Antioxidant activity and phenolic content of betalain extracts from intact plants and hairy root cultures of the red beetroot Beta vulgaris cv. Detroit dark red. Plant Foods Hum Nutr. 2010;65(2):105111. Kanner J, Harel S, Granit R. Betalains--a new class of dietary cationized antioxidants. J Agric Food Chem. 2001;49(11):5178-5185. Ninfali P, Antonini E, Frati A, Scarpa ES. C-glycosyl flavonoids from Beta vulgaris cicla and betalains from Beta vulgaris rubra: antioxidant, anticancer and antiinflammatory activities-a review [published online ahead of print May 2, 2017]. Phytother Res. Campbell N, Clark JP, Stecher VJ, et al. Adulteration of purported herbal and natural sexual performance enhancement dietary supplements with synthetic phosphodiesterase type 5 inhibitors. J Sex Med. 2013;10(7):1842-1849. Eleazu C, Obianuju N, Eleazu K, Kalu W. The role of dietary polyphenols in the management of erectile dysfunction-mechanisms of action. Biomed Pharmacother. 2017;88:644-652.

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ABSTRACT & COMMENTARY

Adding L-Citrulline Increases Plasma L-Arginine in Men Human clinical trial affirms findings from animal studies REFERENCE

Suzuki T, Morita M, Hayashi T, Kamimura A. The effects on plasma L-arginine levels of combined oral L-citrulline and L-arginine supplementation in healthy males. Biosci Biotechnol Biochem. 2017;81(2):372-375. DESIGN

Double-blind, randomized, placebocontrolled trial PARTICIPANTS

Forty-two healthy, non-obese Japanese men aged 20-49; smokers and men who were taking medications or dietary supplements were excluded. The men were randomized to 1 of 4 groups: 1. Placebo (cornstarch) (n = 11) 2. L-citrulline alone, 2.0 g/day (n = 11) 3. L-arginine alone, 2.0 g/day (n = 10) 4. L-citrulline with L-arginine, 1.0 g/day of each (n = 10) PRIMARY OUTCOME MEASURE

Plasma levels of L-arginine after supplementation KEY FINDINGS

One hour after supplementation, all groups had increases in plasma L-arginine levels compared to placebo; however, levels were significantly higher in the combination L-citrulline, L-arginine group (placebo 5.4 ±16.3; combo 121.9 ±46.7; citrulline alone 66.3 ±33.6; arginine alone 72.3 ±31.5). Levels in the combination group were approximately 40% higher than the L-arginine alone group. None of the participants experienced side effects of any of the treatments during the study.

Geo Espinosa, ND, LAc, CNS

PRACTICE IMPLICATIONS While previous animal studies have shown that the combination of L-arginine with L-citrulline increases L-arginine plasma levels, to my knowledge this is the first human clinical trial to demonstrate this effect.1,2 This is clinically significant given the research demonstrating the diverse and important health benefits of L-arginine supplementation in men. Human clinical trials have shown that L-arginine supplementation can help improve erectile dysfunction (ED),3 insulin resistance,4 and sports performance.5 Specific to ED, research demonstrates that men with ED have low serum levels of L-citrulline and L-arginine.6 Reduced nitric oxide concentration is linked to increased risk of erectile dysfunction. Arginine is a nitric oxide precursor, so it makes sense that low levels of nitric oxide synthase substrates such as L-arginine and L-citrulline could positively influence ED.

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Human clinical trials have shown that L-arginine supplementation can help improve erectile dysfunction, insulin resistance, and sports performance.

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There is also evidence that supplemental L-arginine can help prevent and treat cardiovascular disease, which is likely due to its influence on endothelial-derived nitric oxide production.7,8 A 2016 review by Alyavi et al demonstrated clinical benefits of L-arginine supplementation specifically for ischemic heart disease and once again cited synthesis of nitric oxide production as a key mechanism of action.9 Because of past in vitro and in vivo research showing that L-citrulline suppresses arginase activity,10 the researchers of this present study speculate that this could be a potential mechanism that explains the significant increase with the combination of the 2 amino acids. Previous research has demonstrated that oral L-arginine has reduced bioavailability because it is degraded by arginase in the gastrointestinal tract (40%) and liver (15%) on the first pass.11,12 Historically, fairly large doses of L-arginine alone were needed to produce a therapeutic effect in humans. By inhibiting arginase activity via the addition of the L-citrulline, it’s

ABSTRACT & COMMENTARY

likely that more of the L-arginine can pass through the intestines and liver and into the bloodstream. As demonstrated in this study and previous studies, L-citrulline is a precursor of L-arginine and it alone can increase L-arginine levels.13 From a clinical perspective, because we know that L-arginine can positively influence a man’s health, it makes sense to explore this combination. It appears to enhance bioavailability of oral L-arginine supplementation. This was a small study; more research is needed to further confirm this effect.

3 4 5 6 7 8 9 10

REFERENCES

1 Hayashi T, Juliet PA, Matsui-Hirai H, et al. L-citrulline and L-arginine supplementation retards the progression of high-cholesterol-diet-induced atherosclerosis in rabbits. Proc Natl Acad Sci USA. 2005;102(38):1368113686. 2 Morita M, Hayashi T, Ochiai M, et al. Oral supplementation with a combination of L-citrulline and L-arginine rapidly increases plasma L-arginine

11 12 13

concentration and enhances NO bioavailability. Biochem Biophys Res Commun. 2014;454(1):5357. Chen J, Wollman Y, Chernichovsky T, Iaina A, Sofer M, Matzkin H. Effect of oral administration of high-dose nitric oxide donor L-arginine in men with organic erectile dysfunction: results of a double-blind, randomized, placebo-controlled study. BJU Int. 1999;83(3):269-273. Bogdanski P, Suliburska J, Grabanska K, Jablecka A. Effect of 3-month L-arginine supplementation on insulin resistance and tumor necrosis factor activity in patients with visceral obesity. Eur Rev Med Pharmacol Sci. 2012;16:816-823. Koppo K, Taes YE, Pottier A, Boone J, Bouckaert T, Derave W. Dietary arginine supplementation speeds pulmonary VO2 kinetics during cycle exercise. Med Sci Sports Exerc. 2009;41(8):16261632. Barassi A, Corsi Romanelli MM, Pezzilli R, et al. Levels of L-arginine and L-citrulline in patients with erectile dysfunction of different etiology. Andrology. 2017;5(2):256-261. Tousoulis D, Antoniades C, Tentolouris C, et al. L-arginine in cardiovascular disease: dream or reality. Vasc Med. 2002;7(3):203-211. Bahadoran Z, Mirmiran P, Tahmasebinejad Z, Azizi F. Dietary L-arginine intake and the incidence of coronary heart disease: Tehran lipid and glucose study. Nutr Metabol. 2016;13:23. Alyavi AL, Alyavi BA, Sayfiyev NY, et al. Clinical benefits of metabolic therapy of ischemic heart disease with L-arginine supplementation. Saudi J Med Pharm Sci. 2016;2(9):247-249. Romero MJ, Platt DH, Tawfik HE, et al. Diabetes-induced coronary vascular dysfunction involved arginase activity. Circ Res. 2008;102(1):95-102. Wu G. Intestinal mucosal amino acid catabolism. J Nutr. 1998;128(8):1249-1252. O’Sullivan D, Brosnan JT, Brosnan ME. Hepatic zonation of the catabolism of arginine and ornithine in the perfused rat liver. Biochem J. 1998;330(Pt 2):627-632. Schwedhelm E, Maas R, Freese R, et al. Pharmacokinetic and pharmacodynamics properties of oral L-citrulline and L-arginine: impact on nitric oxide metabolism. Br J Clin Pharmacol. 2008;65(1):51-59.

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Health Effects of Anger in Men Cardiovascular consequences, and beyond ABSTRACT The intent of this paper is to discuss the research on the health effects of anger in men. The paper will review studies on the effects of various types of men’s anger and anger expression on the cardiovascular system, which is the most well-studied system affected by anger, including acute coronary pathologies, as well as chronic conditions secondary to anger. Research studies on the effects of men’s anger on the immune system, pain, erectile dysfunction, and risky health behaviors will also be discussed. Understanding the many negative consequences of anger on a man’s body will highlight the importance of addressing this aspect of men’s health when caring for our male patients.

INTRODUCTION Since earliest known cultures, anger was believed to be a source of illness, whether by projection of anger onto supernatural beings or as a method for keeping “moral order.”1 Disease was purported to be the result of anger as a retribution for transgressions of unwanted behavior. In the early 20th century, research began to emerge on these speculations, and inquiry about the health effects of anger began. For example, in 1939 Franz Alexander, a psychoanalyst and a physician, looked at anger as a causative factor for hypertension.2 Subsequently, evidence has accumulated showing that anger has detrimental effects in the body. It is important that physicians know specifically the health risks of both inwardly directed anger and rage expression. An oft-used aphorism (often incorrectly attributed to the Buddha) says, “You will not be punished for your anger, you will be punished by your anger.” How might the body be taking the punishment of an angry temperament? As naturopathic medicine is rooted in understanding the cause of disease, importantly, it is necessary to understand the root of anger in men’s hearts. When a man’s masculinity is challenged he is more likely to act out in anger, which, in turn, makes him feel more masculine.3 Further, a perceived affront to his ability to “have control” versus “to be controlled” stimulates a response of anger.4

Steven M. Rissman, ND ANGER PATHWAYS Anger is simply an emotion, which in itself may not cause harm, if appropriately managed. The problem with anger seems to be in the expression or withholding of expression. Many studies discussed in this article look at trait anger vs state anger; in the former, anger is a character trait, in the latter, it is an acute emotional state.5 In other studies, the effects of anger are assessed based on how it is expressed by the individual experiencing it. When outwardly expressed toward another, anger is commonly referred to in the literature as “anger-out,”5 which is less socially acceptable because at its extreme it causes physical and emotional harm toward women, children, other men, animals, and so on. Angry feelings also get outwardly directed as criticism of others, blaming or shaming others, and preaching to others in the form of outrage. Conversely, anger may be directed inwardly toward the self, possibly even being suppressed or repressed, which is denoted commonly in research literature as “anger-in.”5 Anger-in is also known as enragement, which may take the form of obsessing or fixating on a thought, holding resentments, or an inability to “let go.”6 Self-medicating is another, more subtle articulation of anger-in, which may be germane to naturopathic medicine. Given the social stigma of anger-out, one might anticipate a rise in maladies resulting from non-expression or anger-in, so both anger pathways will be considered. The studies reviewed in this article look specifically at anger, hostility, and cynicism, but it is important to note that depression, anxiety, and anger are difficult to distinguish, especially in men. Some studies have found that anger was a significant indicator of depression in men,7 especially in men who uphold traditional masculine ideologies. Indeed, anger and hostility were found to be significant predictors of depressive symptoms in a 2015 study of college men who adhere to hegemonic or traditional masculine gender norms.8 CARDIOVASCULAR EFFECTS OF ANGER Most research on the health consequences of anger has focused on the cardiovascular system. Given that cardiovascular disease

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(CVD) is the leading cause of mortality in men,9 a thorough exploration of the relationship between anger and CVD is warranted, specifically including the manner in which angerout and anger-in acutely and chronically affect the multifarious cardiac and vascular pathologies. The Framingham Heart Study is a prospective, longitudinal cohort study that began in 1948 and was foundational in cardiovascular epidemiology. Among the findings of the study was the effect of psychosocial factors, including anger, on the cardiovascular system.10 The anger effects on the sympathetic nervous system include increased blood pressure, vasoconstriction of arterioles, and increased blood clotting mechanisms, all of which increase the risk of heart attack and stroke. In addition to increased sympathetic activation, it has been established that anger is associated with greater prothrombotic responses, including more platelet activation and less fibrinolysis, which increases likelihood of a thrombotic occlusion.11-14 In the 1970s, an offshoot of the Framingham Heart Study looked at offspring and spouses of those in the original longitudinal cohort in an attempt to make a predictive relation of anger and hostility to coronary heart disease (CHD), atrial fibrillation (AF), and total mortality risk.15 The study of 1,769 men and 1,913 women (mean age 48.5) found that for men but not women, hostility was positively associated with AF, especially premature AF (prior to age 70). Additionally, the authors found that trait anger was not related to incident CHD but was significantly correlated to total mortality in men, which contradicts some other studies.16,17 In other words, anger as a character trait didn’t increase acute coronary syndromes, but was a contributing factor in overall cardiovascular mortality. One limitation of the study was its predominantly white, middle-aged cohort. A 2015 study, however, at the University of Michigan’s Center for Research on Ethnicity, Culture and Health, showed significant interactions of race and anger.18 Specifically, anger-in, but not anger-out, was associated with cardiovascular mortality in both Blacks and Whites, but more strongly for Whites than Blacks. It was unclear from this study if the cause of the anger association was biological, cultural, or socioeconomic, or if outcomes were related to access to healthcare.

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The immune system is also affected by anger, especially suppressed anger… Given that anger is a common response to a cancer diagnosis, it may be useful to design studies to look at the potential immune system benefits of more effective anger expression in men with various cancers.

”

When looking at the issue of episodic anger explosions, while trait (chronic) anger may not increase the incidence of CHD, an older study (1995) found that anger was capable of triggering a myocardial infarction (MI) within 2 hours.19 Subsequently, a study at the University of Sydney found that there was an 8.5 times higher risk of a coronary event such as atypical pain, heart failure, ST elevation, T-wave inversion and unstable angina within 2 hours of an anger episode.20 The study was an evaluation of data from the National Israel Survey of Acute Coronary Syndromes, conducted in 2004 and completed by 1,849 participants, of whom 1,377 were men. Potential triggers were looked at as predictors of a coronary event, including triggers such as physical exertion, emotional stress, anger, and heavy meals prior to the coronary incident. It is possible that men of older generations would identify more with the term “emotional stress” than specifically with “anger,” which may have influenced the results. Anger was not found to have a significant effect on mortality or rehospitalization, though emotional stress did. Further, the results indicated that anger was a more frequent trigger in subjects younger than 65. Some criticized this study because of its case-crossover design, rather than a case-control design. The study design may have had recall bias, such that patients were trying to pin

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the coronary event to a specific external source such as an argument, rather than looking at long-term personal lifestyle choices such as dietary or exercise habits. What wasn’t included in the discussion was that looking for external causes of anger, rather than internal causes, is typical behavior in men, especially those adhering to traditional masculine norms.8 Perhaps the most comprehensive review and meta-analysis of studies, especially as associated with acute anger, was conducted by European researchers in 2014. The authors concluded that, compared to other periods of time, the risk of MI, acute coronary syndrome (ACS), ischemic and hemorrhagic stroke, and arrhythmia are higher in the 2 hours following outbursts of anger, although the magnitude of the association varied among the reviewed studies.21 This affirms a fairly convincing argument for the implication of acute anger as a risk factor for a cardiovascular event. With respect to mechanisms affecting the vasculature, suppressed anger (anger-in) has been implicated as a risk factor for the development of aortic (P<0.01) and carotid artery (P<0.05) stiffness due to increased intimal-media thickness. The Baltimore Longitudinal study, a small study of only 200 participants, 95 of whom were men, used the Spielberger Anger Expression Inventory to look at the effect of anger on intimal thickness.22 Findings demonstrated that the effects of anger contributed to increased vessel thickening. The likely cause of the thickness was secondary to hypertension, whereas neither trait anger nor outwardly expressed anger showed a correlation. A peculiar finding involves the physiologic acclimation of chronic trait anger, where individuals with high trait anger may actually be less susceptible to cardiovascular risks of an anger outburst because the body acclimates to the chronically heightened sympathetic nervous system. However, those with higher trait anger do have an increased frequency of rage outbursts and also may have greater absolute risk.19 Another pathway for greater cardiovascular mortality due to anger outburst is via increased cortisol levels.23 A 2000 study showed that anger (anger-out) secondary to job strain (high demand with low job control) increased salivary cortisol levels,

which has been shown to be a predictive marker for cardiovascular mortality.24 Although the impact of decreasing stress, increasing relaxation, and incorporating mindfulness are all valuable, job strain is inevitable for some. For these patients, it would be useful for physicians to know the mortality risks due to cardiovascular disease, and to provide naturopathic support for the cardiovascular system. Additionally, the intensity of anger correlated to greater risk for ventricular arrhythmia and MI, thus clinical support toward decreasing anger intensity would be paramount. Those with other known risk factors for cardiovascular disease are at greater risk with anger outbursts.19 Evidence from a 2009 study showed that anger and hostility not only affect healthy individuals, but also contribute to poorer prognosis in those with established CHD.25 In this review of 25 studies on healthy individuals and 19 studies on those with existing CHD, the latter showed a greater risk for the development of harmful effects due to anger. A 2013 review of the Nova Scotia Health Survey looked at anger, cynical distrust, and antagonistic behavior and CHD, and found that even after adjusting for traditional risk factors, men with low constructive anger scores and high destructive anger scores had increased 10-year incident CHD risks.26 Additionally, chronic hostility was found to be a chronic risk factor for the development of hyperlipidemia, hypertension, and heightened sympathetic activity—leading to atherosclerosis. Behavioral and pharmacological interventions were positively correlated with reductions in hostility and diastolic blood pressure, supporting the theoretical use of naturopathic interventions such as botanical medicines, nutritional supplements, and behavior/lifestyle counseling in the primary care setting. Several studies showed that lower levels of education were more commonly found in individuals with anger-associated cardiovascular events.15,19 According to Boylan and colleagues this may be due to greater stressors, along with decreased “cognitive flexibility,” in that those with higher education and higher ability to control their anger were “better able to look at the situation from a different perspective, more likely to

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communicate with the target of anger, and more likely to use active problem solving once angry.”27 All primary care clinicians should recognize that although education level can be a risk factor for cardiovascular events associated with anger, interventions can be crafted to include skills for working with anger, especially in boys and young men, regardless of education level. Many of the aforementioned studies have focused on the acute effects of anger/rage on cardiovascular health, especially in the aging population, but there are other studies that point to the importance of protecting our young men from future development of CVD. In a 2002 prospective study, Chang and colleagues followed 1,055 men for 32 to 48 years and found that a high level of anger in young men in response to stress is associated with premature (prior to age 55) CHD and MI.28 Cardiovascular disease is often associated with aging, but this study shows that prevention of CVD includes moderating anger expression at any age. Anger, in addition to having negative effects on the coronary vessels, can be a causative and an accelerating factor for microvascular disease such as retinal arteropathies.29 Anger, depression (which can be expressed as anger, hostility, and aggression in men), cynicism, and other psychosocial factors are associated with retinopathy, secondary to retinal vascular damage. Retinopathy includes hemorrhages, microaneurysms, ischemia of the retina, and necrosis of the endothelial cells. One study found that participants who had both depressive symptoms and hypertension had 60% greater odds of developing retinopathy, while depressed patients without hypertension had 30% greater odds, compared to controls. This finding does 2 things: it demonstrates the correlation of retinopathy and anger, and it shows that previous history increases the relationship between retinopathy and anger. Interestingly, men with less emotional support showed greater risk for developing retinopathy.27 This is noteworthy because some populations of men, especially those men who tend toward traditional hegemonic masculinities, tend to seek emotional support less frequently. Practitioners must be alert to these associations in male patients with current retinopathy,

diabetics who have increased risks for the development of retinopathy, and those with a tendency toward anger, hostility, depression, or social isolation. These studies affirm that anger is a threat to men’s cardiovascular system and provides evidence that there is much more than simply hypertension as a cause and effect of anger in men. IMMUNE SYSTEM EFFECTS OF ANGER The immune system is also affected by anger, especially suppressed anger. A 2006 study of 61 men with localized prostate cancer suggested a relationship between suppression of anger and natural killer cell cytotoxicity (NKCC).30 Natural killer cell cytotoxicity has been used as a prognostic indicator for cancer progression,31 and while other psychosocial factors have been considered in relationship to NKCC, this study was the first of its kind to look at the effect of anger expression on immune cells in older men. Results of the study showed that less anger suppression, as measured by The Courtauld Emotional Control Scale, was related to greater NKCC.28 Given that anger is a common response to a cancer diagnosis, it may be useful to design studies to look at potential immune system benefits of more effective anger expression in men with various cancers. Another study looked at inflammatory activity (interleukin [IL]-1, IL-6, and interferon gamma [IFN-gamma]) based on induced anxiety and anger. In this 2015 study, researchers found that anxiety, but not anger, increased IFN-gamma and IL-1ß levels in oral mucosal transudate samples following induction by writing about a situation that was anxietyproducing or anger-producing.32 The investigators made the distinction between anxiety as an “avoidant emotion” and anger as an “approach emotion.” However, because not all people experience anger as an approach emotion, and don’t feel “certain and relatively in control of a situation” when in an angry state, the investigators may have made an assumption bias such that anger as an avoidant emotion could also produce increases in proinflammatory cytokines. This may have skewed the results toward what they arbitrarily defined as “anxious” events.

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ANGER AND PAIN Many studies have affirmed a relationship between anger and pain, which over the course of years has become more nuanced, depending on the manner in which anger manifests (anger-in or anger-out). Those who express anger outwardly show greater pain sensitivity than those who express anger inwardly.33,34 In a 2014 study, Burns, Bruehl, and Chont looked more specifically at the physiologic mechanisms that may determine pain response to anger. The study of 146 participants (54% men) looked at the role of endogenous opioid system dysfunction in those with high trait anger, when induced into a state of acute anger. Results of this intricate and quite complex study indicated that people with high trait anger and anger-out tendencies, when induced into an acute episode of anger, actually show lower pain intensity.35 This is intriguing in that it may indicate that people with high trait anger have compromised endogenous opioid analgesia. An anger outburst may therefore be a way to moderate pain, albeit not the optimum way, given the totality of anger’s effects. ANGER AND RHEUMATOID ARTHRITIS/ ASTHMA An April 2016 study looked at anger expression styles and symptom severity in rheumatoid arthritis (RA; joint pain, stiffness, and physical limitation) and asthma (coughing and wheezing). The results showed that especially in men, those with high anger-in had increased frequency and intensity of momentary anger throughout the day.36 The authors also observed that high trait anger-in predicted increased physical limitations and asthma-specific symptoms in daily life, while high trait anger-out predicted reduced RA-specific symptoms. One clinical application of this study would be to employ therapies that encourage anger expression (eg, talk therapy, support groups) to moderate symptoms in men with RA. ANGER AND ERECTILE DYSFUNCTION Although psychosocial factors have correlated strongly with erectile dysfunction (ED) in many studies, a clear correlation has not been established. In a 1991 study, Bozman et al found that anger significantly caused negative

penile tumescence and sexual desire, especially during foreplay.37 Researchers suggested that anger may be the main mechanism responsible for the inhibition of desire and arousal in cases of hypoactive sexual desire. Incidence of impotence (ED) correlated with both increasing expression and suppression of anger. In 2000, an examination of the Massachusetts Male Aging Study found that neither anger-in nor anger-out predicted the occurrence of ED,38 contradicting the Bozman study. However, this study was also designed to look at dominant vs submissive personality and the correlation to ED. The aim of the study was to determine if the trait of dominance independently contributed to the risk of ED 8.8 years later. The results suggest that new cases of ED are much more likely to occur among men who exhibit a submissive personality. Again, this doesn’t correlate to anger, but given the link to masculine roles, it is worth mentioning. One could infer that the lack of a prospective relationship between ED and anger suggests the effects of anger may be more short-lived, an observation that could shed light on many of the acute cardiovascular effects of anger. In a 2010 Italian study of both men and women, trait anger was not found to significantly affect sexual motivation; however, trait anger was positively correlated to sexual interpersonal behavior, especially in men.39 These behavioral variants included neurotic sex, impersonal sex and aggressive sex (P<0.002 for all 3 variants). Another study, also Italian, found that anger-prone individuals are more interested in seeking sexual pleasure than committing to a deep relationship, aiming to satisfy their own needs and desires while neglecting their partners’, engaging in sex without emotional intimacy, commitment, or love.40 In other words, the study found that angry men are more egocentric sexually, are less interested in giving to their partner during sex, are more likely to take pleasure in humiliating their partner during sex, and lack desire for tenderness. Discussing sexual practices with male patients is a sensitive topic; while it may take years to develop such rapport, remaining open to the conversation and listening for clues may help identify anger as an issue to be addressed.

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RISKY HEALTH BEHAVIORS AND ANGER In 2004 Fessler et al established that anger increased risktaking in males, but not in females.41 Subsequently, a study originally published in 2016, in 3 experiments, as well as a meta-analysis, determined that incidental anger in men increased risky behavior. The authors hypothesized that men are more likely to respond to disasters and aggression with anger.42 Based on the experimental design, anger would also lead to real-world correlates such as smoking, substance and alcohol use, gambling, and risky sexual behavior, which carry their own serious health effects. Authors of a 2010 study offer another possible explanation for why men may have more risky behavior with aggression. They found that higher levels of testosterone led to an increase in aggression through a decrease in activity in the medial orbitofrontal cortex during a (non-risky) decision-making paradigm.43 CONCLUSION Over the course of history, research has shown a more clear connection of anger, not simply overt expression but inward expression as well, to a wide array of pathologies. Most of the research has been on cardiovascular pathologies and secondary

conditions of poor cardiovascular health. While the evidence is strongest for acute coronary vessel pathologies such as MI and the cardiovascular effects of increased sympathetic nerve stimulation, especially in the 2 hours following an anger episode, there is also convincing support for consequential effects of trait anger toward cardiovascular damage. As such, physicians would be well-advised to consider anger, hostility, and depressive symptoms as risk factors for the development of CVD, and especially for patients with established CVD. There is evidence for correlations of anger, in its diverse forms, to decreased immune function, specifically NKCC, and increases in pro-inflammatory cytokines. Also, angered patients who express outwardly have greater sensitivity to pain with the interesting finding that those with high trait anger may have dysfunctional endogenous opioid systems. Given the current focus on pain and addictions to opioid pain medications, this is another area that needs further large-scale research. Anger also increases symptomatic expression of RA and asthma, especially in men who tend to hold anger in, which may become increasingly common because of the current decrease in tolerance of men negatively expressing outward

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anger. There was sparse evidence for a strong connection of anger to ED, though more stirring data linked anger to variant sexual behavior in men. Finally, anger in men leads to risky health behaviors, possibly due to the effect of anger on decision-making areas of the brain. In conclusion, there is evidence that anger, in the form of acute anger explosions, chronic hostile anger, or various methods of anger expression, is detrimental to men’s health. Clinicians should heed the evidence on the ramifications of anger in the body and consider therapies that address this aspect of health in men. REFERENCES 1 2 3 4 5

6 7 8 9 10 11 12 13 14 15 16 17

Potegal M, Stemmler G, Spielberger CD, SpringerLink (Online service). International Handbook of Anger: Constituent and Concomitant Biological, Psychological, and Social Processes. New York: Springer; 2010. Alexander F. Psychoanalytic study of a case of essential hypertension. Psychosom Med. 1939;1(1):139-152. Dahl J, Vescio T, Weaver K. How threats to masculinity sequentially cause public discomfort, anger, and ideological dominance over women. Social Psychology. 2015; 46:242-254. Thomas SP. Men’s anger: a phenomenological exploration of its meaning in a middleclass sample of American men. Psychology of Men and Masculinity. 2003;4:163-175. Spielberger CD, Johnson EH, Russell SF, et al. The experience and expression of anger: construction and validation of an anger expression scale. In: Chesney MA, Rosenman RH, eds. Anger and Hostility in Cardiovascular and Behavioral Disorders. New York: Hemisphere/McGraw Hill; 1985:5-30. Lee JH. The Anger Solution: The Proven Method for Achieving Calm and Developing Healthy, Long-lasting Relationships. Boston, MA: Da Capo Press; 2009. Clark LA. The anxiety and depressive disorders: descriptive psychopathology and differential diagnosis. In: Kendall PC, Watson D, eds. Anxiety and Depression: Distinctive and Overlapping Features. San Diego, CA: Academic Press; 1989:83-129. Genuchi M. Anger and hostility as primary externalizing features of depression in college men. Int J Men’s Health. 2015;14:113. Center for Disease Control and Prevention. Leading Causes of Death in Males, 2014. https://www.cdc.gov/men/lcod/2014/race-ethnicity/index.htm. Updated June 27, 2017. Accessed August 2, 2017. Kannel WB, Feinleib M, McNamara PM, et al. An investigation of coronary heart disease in families: the Framingham offspring study. Am J Epidemiol. 1979;110(3):281-290. Steptoe A, Kivimaki M. Stress and cardiovascular disease. Nat Rev Cardiol. 2012; 9(6):360-370. Boltwood MD, Taylor CB, Boutte Burke M, Grogin H, Giacomini J. Anger report predicts coronary artery vasomotor response to mental stress in atherosclerotic segments. Am J Cardiol. 1993;72(18):1361-1365. Markowitz JH. Hostility is associated with increased platelet activation in coronary heart disease. Psychosom Med. 1998;60(5):586-591. Wenneberg SR, Schneider RH, Walton KG, et al. Anger expression correlates with platelet aggregation. Behav Med. 1997;22(4):174-177. Eaker ED, Sullivan LM, Kelly-Hayes M, D’Agostino S, Ralph B, Benjamin EJ. Anger and hostility predict the development of atrial fibrillation in men in the Framingham Offspring Study. Circulation. 2004;109(10):1267-1271. Kawachi I, Sparrow D, Spiro 3, A, Vokonas P, Weiss ST. A prospective study of anger and coronary heart disease. The Normative Aging Study. Circulation. 1996;94:20902095. Williams JE, Paton CC, Siegler IC, Eigenbrodt ML, Nieto FJ, Tyroler HA. Anger proneness predicts coronary heart disease risk: prospective analysis from the atherosclerosis risk in communities (ARIC) study. Circulation. 2000;101:2034-2039.

18 Assari S. Hostility, anger, and cardiovascular mortality among Blacks and Whites. Res Cardiovasc Med. 2016;6(1):e34029. 19 Mittleman MA, Maclure M, Sherwood JB, et al. Triggering of acute myocardial infarction onset by episodes of anger. Circulation. 1995;92(7):1720-1725. 20 Tofler GH, Kopel E, Klempfner R, Eldar M, Buckley T, Goldenberg I; National Israel Survey of Acute Coronary Syndrome Investigators. Triggers and timing of acute coronary syndromes. Am J Cardiol. 2017;119(10):1560-1565. 21 Mostofsky E, Penner EA, Mittleman MA. Outbursts of anger as a trigger of acute cardiovascular events: a systematic review and meta-analysis. Eur Heart J. 2014; 35(21):1404-1410. 22 Anderson DE, Metter EJ, Hougaku H, Najjar SS. Suppressed anger is associated with increased carotid arterial stiffness in older adults. Am J Hypertens. 2006;19(11):11291134. 23 Pahuja R, Kotchen TA. Salivary cortisol predicts cardiovascular mortality. Cur Hypertens Rep. 2011;13(6):404-405. 24 Steptoe A, Cropley M, Griffith J, Kirschbaum C. Job strain and anger expression predict early morning elevations in salivary cortisol. Psychosom Med. 2000; 62(2):286-292. 25 Chida Y, Steptoe A. The association of anger and hostility with future coronary heart disease: a meta-analytic review of prospective evidence. J Am Coll Cardiol. 2009; 53(11):936-946. 26 Suls J. Anger and the heart: perspectives on cardiac risk, mechanisms and interventions. Prog Cardiovasc Dis. 2013; 55(6):538-547. 27 Boylan JM, Ryff CD. Varieties of anger and the inverse link between education and inflammation: toward an integrative framework. Psychosom Med. 2013;75(6):566-574. 28 Chang PP, Ford DE, Meoni LA, Wang N, Klag MJ. Anger in young men and subsequent premature cardiovascular disease: the precursors study. Arch Int Med. 2002; 162(8):901-906. 29 Jensen RA, Shea S, Ranjit N, et al. Psychosocial risk factors and retinal microvascular signs: the multi-ethnic study of atherosclerosis. Am J Epidemiol. 2010;171(5):522-531. 30 Penedo FJ, Dahn JR, Kinsinger D, et al. Anger suppression mediates the relationship between optimism and natural killer cell cytotoxicity in men treated for localized prostate cancer. J Psychosom Res. 2006;60(4):423-427. 31 Levy EM, Roberti MP, Mordoh J. Natural killer cells in human cancer: from biological functions to clinical applications. J Biomed Biotechnol. 2011;2011:676198. 32 Moons WG, Shields GS. Anxiety, not anger, induces inflammatory activity: An avoidance/approach model of immune system activation. Emotion. 2015;15(4):463-476. 33 Bruehl S, Burns JW, Chung OY, Ward P, Johnson B. Anger and pain sensitivity in chronic low back pain patients and pain-free controls: the role of endogenous opioids. Pain. 2002; 99(1-2):223-233. 34 Bruehl S, Chung OY, Burns JW, Diedrich L. Trait anger expressiveness and paininduced beta-endorphin release: support for the opioid dysfunction hypothesis. Pain. 2007;130:208-215. 35 Burns JW, Bruehl S, Chont M. Anger regulation style, anger arousal and acute pain sensitivity: evidence for an endogenous opioid “triggering” model. J Behav Med. 2014; 37(4):642-653. 36 Russell MA, Smith TW, Smyth JM. Anger expression, momentary anger, and symptom severity in patients with chronic disease. Ann Behav Med. 2016;50(2):259-271. 37 Bozman AW, Beck JG. Covariation of sexual desire and sexual arousal: the effects of anger and anxiety. Arch Sex Behav. 1991;20(1):47-60. 38 Araujo AB, Johannes CB, Feldman HA, Derby CA, McKinlay JB. Relation between psychosocial risk factors and incident erectile dysfunction: prospective results from the Massachusetts Male Aging Study. Am J Epidemiol. 2000;152(6):533-541. 39 Muscatello MR, Bruno A, Scimeca G, et al. The relationship between anger and heterosexual behavior. An investigation in a nonclinical sample of urban Italian undergraduates. J Sex Med. 2010;7(12):3899-3908. 40 Iannuzzo G, Pandolfo G, Bonadonna A, et al. The relationship between anger and sexual behavior: a review of theories and research. MJCP. 2014;2(1). 41 Fessler DMT, Pillsworth EG, Flamson TJ. Angry men and disgusted women: an evolutionary approach to the influence of emotions on risk taking. Org Behav Hum Dec Proc. 2004;95:107-123. 42 Ferrer RA, Maclay A, Litvak PM, Lerner JS. Revisiting the effects of anger on risk-taking: empirical and meta-analytic evidence for differences between males and females. J Behav Dec Mak. 2017;30:516-526. 43 Mehta PH, Beer J. Neural mechanisms of the testosterone–aggression relation: the role of orbitofrontal cortex. J Cognitive Neurosci. 2010;22:2357-2368.

AUDIO INTERVIEW

Addressing Male Urinary Incontinence A conversation with men’s health expert Ronald A. Morton, Jr., MD, FACS Play Now http://www.naturalmedicinejournal.com/sites/default/files/media/nmj_ron_morton_podcast_audio_only.mp3 Approximate listening time: 14 minutes

ABOUT THE INTERVIEW Although urinary incontinence is not as common in men as it is in women, it is more prevalent than many people think. According to the Centers for Disease Control and Prevention, 1 in 4 men over the age of 65 suffers from it. The underlying causes are often similar in both genders: aging and weakening of the pelvic floor muscles. However, pelvic trauma or prostate disease or surgery can also contribute to the problem in men. Urinary incontinence creates significant quality-of-life issues, so finding effective treatments is very important. In this interview with urologist Ronald A. Morton, Jr., MD, FACS, Natural Medicine Journal’s publisher Karolyn A. Gazella discusses the prevailing treatment options for male urinary incontinence. For some men, pelvic floor exercises alone can provide relief. For others, diet and weight modification are necessary. Others may opt for more advanced interventions, including medical devices. Surgical medical device options range from minimally invasive to extensive. On the simpler end of the spectrum is the basic urinary sling. In this quick procedure, a sling is inserted to replicate the support lost in previous interventions or trauma. On the other end of the spectrum is an artificial urinary sphincter, which regulates urine flow through a pump. Of course, surgical interventions are not without risks and side effects. Morton addresses those and discusses how to determine whether a patient is a good candidate for surgery. Listen to this interview to learn more about the current treatment options for male urinary incontinence, as well as Morton’s predictions for the future of incontinence treatment.

ABOUT THE EXPERT RONALD A. MORTON, JR, MD, FACS, is the vice president of clinical sciences for the Urology and Pelvic Health division of Boston Scientific, a position that he has held since August 2015. Before joining Boston Scientific, via acquisition, Morton worked for Endo International plc as chief surgical officer, American Medical Systems. Previously, he worked for GTx, a biotech company in Memphis, TN, as chief medical officer. Prior to joining GTx, Morton was chief of urology at Robert Wood Johnson Medical School and director of urologic oncology for the Cancer Institute of New Jersey. He also held an endowed chair position as director of the General Clinical Research Center. Morton holds a BA in natural sciences from The Johns Hopkins University and received his medical doctorate from The Johns Hopkins University School of Medicine. He has board certification as a diplomat, American Board of Urology.

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AUDIO INTERVIEW

Erectile Dysfunction’s Clues About Cardiovascular Health Interview with Daniel Chong, ND Play Now http://www.naturalmedicinejournal.com/sites/default/files/media/dan_chong_on_2017-07-24_at_09.07.mp3 Approximate listening time: 30 minutes

ABOUT THE INTERVIEW It may seem counterintuitive to interview a cardiologist, and not a urologist, on the topic of erectile dysfunction (ED). But we now know that ED is a result of endothelial cell dysfunction and ED can be an early warning sign of systemic atherosclerosis. Looking at ED from a cardiovascular perspective is essential. That’s why we invited cardiovascular expert Daniel Chong, ND, to talk to us about ED’s connection to heart health. In this interview, Natural Medicine Journal’s editor-in-chief, Tina Kaczor, ND, FABNO, asks Chong about the complex interplay between vascular function and sexual function. According to Chong, cardiovascular disease always has some degree of contribution—potentially a major one—in ED. That’s in part because blood flow is the key facet to obtaining a full erection. Cardiovascular dysfunction, including plaque in the arteries that regulate that blood flow, can therefore have an impact on ED. Even before plaque development becomes a problem, endothelial dysfunction in the inside walls of the arteries can play a role in erectile function. In this enlightening interview, Chong explains the different issues that can contribute to ED, including anatomical, physiological, and psychological problems. It’s an important listen for any practitioner who sees men, since beyond being a problem in and of itself ED can be an early signal of other serious health concerns.

ABOUT THE EXPERT DANIEL CHONG, ND, has been

a licensed naturopathic physician, practicing in Portland, Oregon, since 2000 and focusing on risk assessment, prevention, and drug-free treatment strategies for cardiovascular disease and diabetes, as well as general healthy aging, and acute and chronic musculoskeletal injuries. Chong has also completed certificate training in cardio-metabolic medicine from the American Academy of Anti-Aging Medicine and is an active member of the Society for Heart Attack Prevention and Eradication (SHAPE). In addition to his clinical work, Chong serves as a clinical consultant for Boston Heart Diagnostics Lab.

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