Stress

 

How do you feel when I mention the word "stress"? It's possible the word itself might cause your shoulders to flex and your heart to race. Stress has been linked to poor health outcomes. Even for those who don't have serious health issues, stress can make life complicated and difficult. Today on the Integrated Pharmacist Podcast, I want to talk about what stress is and how we can manage it appropriately with complementary and alternative medicine.

Everybody deals with some level of stress. Whether it's from work or school demands, taking care of your home and loved ones, negative changes in your environment or traumatic events, stress can have mental, emotional, and even physical consequences. But not all stress is brought on by negative things. Even enjoyable experiences can bring on stress - weddings, family vacations, and financial gains can contribute to a person's stress.

But not all stress is bad! We actually need some stress. As a short term response to negative experiences, stress helps us get out of immediate dangers. If you encounter a bear in the woods, you need stress to get your muscles and brain oxygenated and functioning at peak capacity. Stress makes your vision focused and your responses heightened. In a more mundane setting, you benefit from a boost of stress when you are being tested at school, interview for a new position, or have a child who suddenly throws up.

Stress also keeps us motivated. It keeps us from being couch potatoes. Literally, the hero of every story faces some kind of stress that motivates them into their journey. Stress is inevitable. It's a part of life. It provides the motivation to get through life's experiences and take on adventures.

When we encounter chronic stress and we don't manage it well, that's when it starts interfering with our health. If you push the gas peddle of your car all the way down and keep it there, eventually you'll burn up the engine. The same goes for the human body. If we keep our bodies in fight-or-flight mode all day, it's going to have some major negative effects. Today, I hope to find some solutions that allow us to shift from fight-or-flight into rest-and-digest mode while still managing daily expectations.

There are several trials indicating the power of meditation. Published in the Journal of Occupational Health Psychology, one study looked at 238 employees from 2 large companies in the UK. They were randomized into using a mindfulness meditation smartphone app or a wait-list control group. Participants in the experimental arm were asked to use the Headspace app to listen to one session a day for 8 weeks (that's 40 work-days) among 45 prerecorded meditations lasting 10-20 minutes. They averaged 17 usages in that time. Interestingly, the older the participant was, the more sessions they were likely to have finished. Participants found benefit in self-reported measures of well-being, daily positive emotions, anxiety symptoms, depressive symptoms, job strain, and workplace social support. Interestingly, job strain was defined as the two factors of job demand and job control. Although demand remained stable, control improved which could be interpreted to mean the participants found that there was no change in how much work they had to do but there was a change in their perceptions of their ability to tackle the job. This demonstrates that even small amounts of time multiple times a week can have a significant impact on stress reduction.

My search for studies on stress led me to fascinating research looking at exercise' influence on stress and stress' influence on exercise. Seventy nine adults ages 20-40 were tracked for an entire year through survey administered by smartphone and through a Fitbit. Although participation varied across the year for each participant, some trends did emerge. The study found that generally speaking, perceived stress the night before tended to reduce the likelihood of exercising on a given day. Likewise, exercising tended to be followed by a period of reduced perceived stress. Because participation was so small, the researchers were able to look at data gathered for each individual. For some people, the opposite phenomenon emerged while others' stress and exercise were unaffected. Although the researchers gathered an extensive psychosocial background, they were unable to find any correlation to explain why the participants had unique experiences when it comes to exercise and stress.

To reinforce the benefit of both meditation and exercise, I'd like to draw your attention to another study published in April of 2019. This study measured specific inflammatory markers associated with stress in 413 participants split into 3 different groups: exercise, mindfulness meditation, and wait list. Their research came to the conclusion that exercise decreased serum interferon-gamma-inducible protein-10 while mindfulness reduced C-reactive protein. Significantly, there was no determination that the amount of either exercise or meditation had a baring on these decreases - which is to say, it's not dose dependent. The conclusion I draw from this is that it's important to use several methods to reduce stress in order to get a more complete benefit from a biochemical standpoint.

There is also a growing body of evidence that associates natural outdoor environments (or NOE) with positive mood and associated health benefits. NOEs can be defined as green or plant-rich environments and blue or water-rich environments. In 2017, additional research was published concerning 26 participants exposed to urban, green, or blue environments in the area of Catalonia, Spain. The goal of this study was to try to find why natural environments have the beneficial effects they do. The researchers used a multi-cross-over style procedure exposing each participant to each environment on different weekends. They measured a variety of physiological and psychological parameters including salivary cortisol levels at several points each day they were exposed to an environment. They found that exercise and air quality had effects on some of the biochemical readings, but some of the benefits remained unexplained. Interestingly, although both green and blue environments reduced perceived stress, green showed significant lowering of salivary cortisol, and green and blue modulated heart-rate variability in different ways. Again, it looks like we may benefit from a wide variety of stress-reducing activities.

Next, I'd like to bring up one of my favorite modes of de-stressing - massage. A study from Brazil published in 2016 looked at 101 participants split into 3 intervention groups - massage + rest, massage + reiki, and control group. Researchers for this study looked at subjective measures of stress and anxiety and the main massage intervention was Anma massage performed by students at a complementary health school. By using this method, it allows for similar interventions for each participant, because the student therapists are more likely to perform the intervention close to how it was taught. Participants were volunteers seeking ambulatory care and military personnel stationed near the school. They came in for interventions twice a week for 1 month. Although there was no statistical difference between the two intervention arms, both did demonstrate significant improvements over the control.

Now I'd like to shift into products one might buy to help with stress. First, I'd like to look at aromatherapy and music. I found a study performed at a nursing school with 98 participants split 3 ways into aromatherapy, music, or both treatments. Test-taking for nursing classes were used as stress-inducers. The aromatherapy chosen was marjoram and orange oil and the music selected was Beethoven's Moonlight Sonata. Both of these interventions do have clinical precedence. Exposure to treatment was via admittance to a room where the essential oil was infused into the air and/or music was played overhead for 20 minutes. Stress measures were evaluated before and after intervention. Although single interventions had equal efficacy, researchers did find statistical improvements with the combined therapy. Although measures were taken to blind participants and researchers, obviously participants became aware of which arm they were in with treatment perception. Also, most participants were young women, so external validity is limited.

There are several supplements and herbs that can help with stress as well. Green tea and L-theanine, a specific chemical found in green tea have both been studied for the reduction of stress in otherwise healthy adults. For L-theanine, 30 participants were randomized in a double blind crossover trial. The experimental arm received 200mg of the synthetically developed chemical while the control received a matching placebo for 4 weeks. There was a 2 week washout period which was determined by the 65-hour 1/2 life for blood L-theanine following which the participants crossed over to the opposite arm for 4 more weeks. Improvements were found in stress-related mood, cognitive function, sleep quality, and verbal fluency in the experimental arm. The subjects who had worse initial test results tended to have the most improvement in all areas. There are some concerns about the validity of this trial due to size and overall good health of participants. Similarly, green tea was studied in a 4 week crossover trial of two groups in Japan testing standard green tea against low-caffeine green tea. The low-caffeine green tea was prepared by washing fresh green tea leaves in hot water to pull out caffeine before standard tea leaf processing. Participants drank one or the other of the green tea preparations all day long for 1 week preceded by a washout week of drinking only water. At the conclusion of the study, it was found that when participants took low-caffeine green tea, they experienced lower stress and better sleep. Study researchers propose the mechanism is due to lower caffeine and a higher ratio of theanine compared to caffeine.

A meta analysis looking at the mood modulating effects of B complex vitamins found significance in stress reduction. Of the 10 studies they found, 6 of them showed significant difference based on 3 different stress-measuring tools. Heterogeneity was at 60% across studies and chi square was violated which means there was not enough appropriate data to completely trust the results of the analysis.

Hemp is another popular herb lately. A study published last year in the Journal of Dietary Supplements gave 65 overweight but otherwise healthy participants either 60mg hemp enhanced with an extra 15mg of CBD, or a matching placebo. Over the 6-week trial, participants were encouraged to maintain their regular lives. At the end of the trial, participants on the hemp oil reported better and longer sleep and improved perceptions of positivity to their life and ability to cope with stress.

Ayurvedic medicine brings a unique intervention in the form of adaptogens. An adaptogen is an herb that purports to help the body's systems back to homeostasis. Specifically, they are taken to deal with stresses from the environment of any kind - from temperature, to physical weight, to emotional attack. The Indian Journal of Psychological Medicine published research in 2012 studying the effects of twice daily dosing of 300mg full-spectrum high-concentration Ashwagandha root extract. In a randomized, placebo-controlled trial running 60 days, 64 study participants had blood cortisol levels and clinical psychological test results checked in 15 day intervals. Participants were screened for any clinical psychological illness, but experienced chronic stress. At the end of the study, highly significant differences were detected on both cortisol and test results in favor of the Ashwagandha root extract. The study found the intervention to be highly tolerable with minimal side effects beyond what the placebo arm experienced.

The last trial I'd like to address looks at the effects of valerian and kava. Fifty four university students volunteered for the study. The students were fitted for monitoring equipment and sat for 5 minutes to get a baseline. A 6-minute test was administered that was designed to induce stress. Vital signs were taken several times throughout the test and a questionnaire was performed before and after the test. After the first test, students were randomized to receive 1 tablet of Kava 120mg, 2 tablets of Valerian 600mg, or nothing - which would be a non-placebo. After a full week of those daily doses, the students returned to take the same test under the same conditions. Perceived pressure was significantly reduced after intervention for both experimental arms and several physiological measures were significantly impacted by both interventions. Participants in both groups reported calmer feelings before beginning the second test compared to the control group and rated the test as less stressful the second time around. The control group reported the second test equally stressful compared to the first. Interestingly, the Valerian group showed slower heart rate during the second test as compared to the first test while no change was detected for the other two arms.

To summarize, there are several methods we can use to reduce stress. Meditation, exercise, and getting into nature are free or inexpensive ways to modify how we perceive stressful situations. Specifically, the Headspace app has clinical evidence suggesting its usefulness in the workplace. It seems important to find a form of exercise that is enjoyable and works with your schedule and abilities. It also looks like we could benefit from a variety of different ways of reducing stress. Massage, music and aroma therapies (specifically marjoram and orange oil) could also be used to reduce stress. To be clear, Midnight Sonata has the clinical evidence for auditory stress reduction. I should also add, these specific modalities are anchored in 3 major senses. It's important to note that those who cannot hear well will not respond to music therapy very well and it is unclear whether aroma therapy will work for those without a sense of smell. The same could be said for those who are averse to touch in massage therapy. The question of whether reiki is effective for stress remains unanswered. Daily intake of L-theanine 200mg or the equivalent in low-caffeine green tea could be an enjoyable way of staying calm. B vitamins have also demonstrated their role in managing stress. If a patient is looking for something they can consume for short-term stress reduction, hemp oil 60mg daily, valerian 600mg twice a day, and kava 120mg daily all seem to be useful. If a more long-term option is being sought, concentrated ashwagandha 300mg twice a day might do the trick.

It's important to note that everyone experiences stress in their own way. Like pain, this is a self-reported experience. Therefore, it's likely highly influenced by the placebo effect. I think this is why it's so important to tailor the treatment to the individual and choose a variety of ways to reduce stress rather than going with just 1 method for everybody. For example, we know exercise and movement positively influence psychological and physiological measures of stress, but not everyone will benefit from a long cardio routine or pumping iron. On the other hand, not everyone will get full benefit from yoga or taichi, either. For patients dealing with chronic stress, I highly recommend finding an enjoyable exercise regimen that works with their schedule. Regular (though not necessarily daily) meditation and access to nature should be woven into their schedule, too. Based on sensory preferences, effort could be made in finding enjoyable touch, sound, and smell stimulation based on acute needs. To enhance these modalities, oral supplements can be added for acute and chronic stress management. It's good to know there are several options in oral treatments, so if one doesn't work due to allergy or ineffectiveness, there are other options.

This was an important episode for me. Stress is nearly ubiquitous and I've certainly had my fair share. The last 5 years especially, I have worked full-time while going to accelerated pharmacy school and had 2 out of 5 children born during that time. In the middle of that, I was in the building of a mass shooting and diagnosed with OCD. And of course the world crisis brought on by Covid-19 has affected everyone's lives. Despite my trials and reasons to harbor stress, I feel like I've dealt with it pretty well. Looking back, the few moments I did have for stress management were spent doing the activities I found in the research I brought to your attention today. Some of my fondest memories of that time were taking my family to Mt. Charleston outside Las Vegas to enjoy the trees and cooler weather. My home was filled with peaceful music and sweet fragrances due mostly to my knowledgeable and wise wife. Now that I have the clinical background to support how I got through my stressful times, I hope to help others like me do the same. If you or someone you know is a father who is looking for help with stress management, stay tuned. I am developing a program to do just that.

Thank you, as always for listening. I hope you enjoyed listening and I you found it useful. If you know someone who would be interested in listening, please pass along my podcast. It also helps me grow if you leave a positive rating and review on itunes. Thanks again and we'll see you next time on the integrated pharmacist podcast.

References:

Bostock, S., Crosswell, A. D., Prather, A. A., & Steptoe, A. (2019). Mindfulness on-the-go: Effects of a mindfulness meditation app on work stress and well-being. Journal of Occupational Health Psychology, 24(1), 127–138. https://doi.org/10.1037/ocp0000118

Matthew M. Burg, PhD, Joseph E. Schwartz, PhD, Ian M. Kronish, MD, Keith M. Diaz, PhD, Carmela Alcantara, PhD, Joan Duer-Hefele, MA, Karina W. Davidson, PhD, Does Stress Result in You Exercising Less? Or Does Exercising Result in You Being Less Stressed? Or Is It Both? Testing the Bi-directional Stress-Exercise Association at the Group and Person (N of 1) Level, Annals of Behavioral Medicine, Volume 51, Issue 6, December 2017, Pages 799–809, https://doi-org.roseman.idm.oclc.org/10.1007/s12160-017-9902-4

Meyer JD, Hayney MS, Coe CL, Ninos CL, Barrett BP. Differential Reduction of IP-10 and C-Reactive Protein via Aerobic Exercise or Mindfulness-Based Stress-Reduction Training in a Large Randomized Controlled Trial. J Sport Exerc Psychol. 2019 Apr 1;41(2):96-106. doi: 10.1123/jsep.2018-0214. Epub 2019 Apr 26. PMID: 31027457; PMCID: PMC6777863.

Young LM, Pipingas A, White DJ, Gauci S, Scholey A. A Systematic Review and Meta-Analysis of B Vitamin Supplementation on Depressive Symptoms, Anxiety, and Stress: Effects on Healthy and 'At-Risk' Individuals. Nutrients. 2019 Sep 16;11(9):2232. doi: 10.3390/nu11092232. PMID: 31527485; PMCID: PMC6770181.

Son HK, So WY, Kim M. Effects of Aromatherapy Combined with Music Therapy on Anxiety, Stress, and Fundamental Nursing Skills in Nursing Students: A Randomized Controlled Trial. Int J Environ Res Public Health. 2019 Oct 29;16(21):4185. doi: 10.3390/ijerph16214185. PMID: 31671873; PMCID: PMC6861884.

Kurebayashi LF, Turrini RN, Souza TP, Takiguchi RS, Kuba G, Nagumo MT. Massage and Reiki used to reduce stress and anxiety: Randomized Clinical Trial. Rev Lat Am Enfermagem. 2016 Nov 28;24:e2834. doi: 10.1590/1518-8345.1614.2834. PMID: 27901219; PMCID: PMC5172615.

Unno K, Noda S, Kawasaki Y, Yamada H, Morita A, Iguchi K, Nakamura Y. Reduced Stress and Improved Sleep Quality Caused by Green Tea Are Associated with a Reduced Caffeine Content. Nutrients. 2017 Jul 19;9(7):777. doi: 10.3390/nu9070777. PMID: 28753943; PMCID: PMC5537891.

Hidese S, Ogawa S, Ota M, Ishida I, Yasukawa Z, Ozeki M, Kunugi H. Effects of L-Theanine Administration on Stress-Related Symptoms and Cognitive Functions in Healthy Adults: A Randomized Controlled Trial. Nutrients. 2019 Oct 3;11(10):2362. doi: 10.3390/nu11102362. PMID: 31623400; PMCID: PMC6836118.

Hidese S, Ogawa S, Ota M, Ishida I, Yasukawa Z, Ozeki M, Kunugi H. Effects of L-Theanine Administration on Stress-Related Symptoms and Cognitive Functions in Healthy Adults: A Randomized Controlled Trial. Nutrients. 2019 Oct 3;11(10):2362. doi: 10.3390/nu11102362. PMID: 31623400; PMCID: PMC6836118.

Triguero-Mas M, Gidlow CJ, Martínez D, de Bont J, Carrasco-Turigas G, Martínez-Íñiguez T, Hurst G, Masterson D, Donaire-Gonzalez D, Seto E, Jones MV, Nieuwenhuijsen MJ. The effect of randomised exposure to different types of natural outdoor environments compared to exposure to an urban environment on people with indications of psychological distress in Catalonia. PLoS One. 2017 Mar 1;12(3):e0172200. doi: 10.1371/journal.pone.0172200. PMID: 28248974; PMCID: PMC5331968.

Nishida K, Sawada D, Kuwano Y, Tanaka H, Rokutan K. Health Benefits of Lactobacillus gasseri CP2305 Tablets in Young Adults Exposed to Chronic Stress: A Randomized, Double-Blind, Placebo-Controlled Study. Nutrients. 2019 Aug 10;11(8):1859. doi: 10.3390/nu11081859. PMID: 31405122; PMCID: PMC6723420.

Hector L. Lopez, Kyle R. Cesareo, Betsy Raub, A. William Kedia, Jennifer E. Sandrock, Chad M. Kerksick & Tim N. Ziegenfuss (2020) Effects of Hemp Extract on Markers of Wellness, Stress Resilience, Recovery and Clinical Biomarkers of Safety in Overweight, But Otherwise Healthy Subjects, Journal of Dietary Supplements, 17:5, 561-586, DOI: 10.1080/19390211.2020.1765941

Cropley, M., Cave, Z., Ellis, J. and Middleton, R.W. (2002), Effect of Kava and Valerian on human physiological and psychological responses to mental stress assessed under laboratory conditions. Phytother. Res., 16: 23-27. https://doi-org.roseman.idm.oclc.org/10.1002/ptr.1002

Chandrasekhar K, Kapoor J, Anishetty S. A prospective, randomized double-blind, placebo-controlled study of safety and efficacy of a high-concentration full-spectrum extract of ashwagandha root in reducing stress and anxiety in adults. Indian J Psychol Med 2012;34:255-62