Sleep, Stress and the Adrenal Glands

Lifestyles Are Compromising Immune Function; Part 4 of Our Immune Health Series

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Your customers have one thing in common; they want to feel good. As we’ve learned throughout our editorial series on immune health, there are a variety of approaches when it comes to supporting one’s immune health, but perhaps the most obvious and least explored impacts are lack of sleep and chronic stress.

Vicious Cycle of Poor Sleep and Chronic Stress
Sleep is paramount. While we all understand the value of a good night’s sleep, it may be rare that one actually gets the recommended eight hours of sleep per night. Our society has developed a culture that prides itself on working hard while sacrificing luxuries such as sleep to accomplish our goals. This is especially true of the young and ambitious. Unfortunately, a lack of sleep doesn’t make us better in any way.

“When I’m working with patients, if they tell me they are also not sleeping, sleep gets moved to the top of that list because I know I’m only going to get so far with people when they’re not sleeping, that’s going to be an obstacle to reaching their other goals,” explains Aimée Gould Shunney, ND, licensed naturopathic doctor, and medical adviser for CV Sciences, based in San Diego, CA. “If we’re not sleeping well, we’re more likely to be overweight, depressed, to have inflammation in our bodies — which is the root cause for all chronic illness. So I think there is a deep relationship between general health, immune health, self care and sleep being an extremely important part of that.”

Unfortunately, people are often reactive instead of proactive. It is those feelings of exhaustion and sluggishness that make one turn to caffeine, the same way the onset of illness brings us to the drug store for a heavy dose of vitamin C or an over-the-counter cough syrup. Sleep as it turns out is one of our best defenses.

“Specific to the immune system, the circadian rhythm drives an increase in the circulation (resting) and tissue recruitment (wakefulness) of critical white blood cells and is accompanied by enhanced ability to fight off inflammatory damage and infection,” says Jennifer Cooper, VP R&D and quality for Twinlab Consolidated Corp., based in Hauppauge, NY. For example, she explains that exposure to bacteria at the end of a sleep cycle is less likely to result in disease than if the exposure occurs at the beginning.

While poor sleep may be a bad lifestyle choice, it may also be the result of chronic stress. On a daily basis, we are all subject to a variety of stressors that make us anxious. This could range from nearly avoiding a collision on the morning commute to  anticipating a tight deadline for a project at work. Of course, the body’s stress response is a normal and important function. “A short-term, intense burst of tension or anxiety is considered ‘good stress’ because it would provide a temporary extra boost of energy or alertness, which in turn may be helpful in increasing performance,” says Shaheen Majeed, president, Sabinsa Corp., based in East Windsor, NJ. However, when stress becomes prolonged and consistent, this can become a real problem. “People who experience high levels of stress will have dysregulation of the immune system; consequently they become vulnerable to infectious diseases,” adds Majeed.

If you don’t sleep enough at night, your body boosts its levels of stress hormones.

To understand how chronic stress affects the body, it’s important to understand the function of adrenal glands. These are two glands resting on top of the kidneys that are in direct communication with the brain, specifically the pituitary gland at its base.

A part of the endocrine system, the adrenal glands are responsible for what is known as “fight or flight.” Shunney explains, “The hypothalamus is a part of your brain that basically decides if you’re safe or in danger… So you’ve got this loop between the hypothalamus and the endocrine organs via the pituitary. When your brain is perceiving that there’s lots of stress, danger, fight or flight, it’s telling the pituitary gland to make more stress hormones so the pituitary gland makes the precursor hormones that then go and talk to the adrenals and say ‘make cortisol’ or ‘make adrenaline,’ also called epinephrine.”

This loop is also known as the HPA axis and the mechanism dates back to our earliest ancestors who depended on “fight or flight” to fight off or flee from predators. In those times, however, humans had more opportunity to burn off stress hormones because they had greater physical activity and were more in tune with their circadian rhythm. Now, stimuli that activate an adrenal response are different, certainly less intense than predators (most of the time), but can also be much more persistent, keeping one on edge throughout the day. Surely it’s not unusual to experience irritability after a long day at work, which then extends into the night preventing the desired restful sleep.

Physiologically, explains Virender Sodhi, MD (Ayurveda), ND, CEO of Ayush Herbs Inc, this is because “when your body is producing too much cortisol your body is not producing enough melatonin and serotonin, the normal hormones of repair as well as good sleep. So when you’re not creating enough of these hormones your body is not repairing on a regular basis.”

Where it becomes a vicious cycle, says Hank Cheatham, VP marketing and sales, Daiwa Health Development, Inc. Gardena, CA, is “if you don’t sleep enough at night, your body boosts its levels of stress hormones. The brain chemicals connected with deep sleep are the same ones that tell the body to stop the production of stress hormones. As a result, when you don’t sleep well, your body keeps pumping out those hormones. The next day, you feel more stressed, the following night you find it harder to fall asleep, and so on.”

Cooper agrees. “Studies have shown that sleep deprivation mildly activates the HPA axis,” she states. “This collaborative balance between the endocrine and central nervous system is responsible for the body’s ability to adapt to stress. Both adrenocorticotropic hormone and corticosterone concentrations rise in conjunction with sleep deprivation.”

This overactivity of the adrenal glands has become known as “adrenal fatigue,” though Holly Lucille, ND, RN and member of the Science and Advisory Board for EuroPharma, based in Greenbay, WI, prefers to frame this in a different way. “I don’t think the adrenals ever get fatigued and I think it’s important that we talk about it that way because what’s really happening is that our body has this ability to adapt, so I would say it’s an overadaptation, or an adrenal disregulation that’s happening more,” she explains.

The “fatigue” is our own, a result of this adaptation. “Those stress hormones stay elevated for long periods of time so that constant feeling of being ‘stressed out’ [and] poor sleep start to become a pattern and can over time actually create a disconnect with the way the brain communicates with adrenals so that we stop really responding to the same message anymore and instead of being anxious and having insomnia all the time, we get really tired,” explains Shunney.

Natural Solutions
Supporting one’s immune health is so much more than taking dietary supplements. This is particularly true regarding sleep and stress. Lifestyle factors need lifestyle solutions. “What I certainly see in my practice, the more that people are able to take care of themselves, the less they get sick,” says Shunney. “Looking across the board at lifestyle, a lot of what those people have in common is that they’re watching what they eat, they’re moving their bodies, they are sleeping and they have some mechanism in their life for management of stress.”

However, dietary supplements are an important tool to help achieve these goals. While they cannot cure or treat disease and customers should always consult a doctor when contemplating a new supplement regimen, many are turning toward natural solutions. This is particularly true of sleep because people are wary of sleep medications for fear of developing a dependence.

“There is great interest in the market for ingredients that have more elegant and gentler mechanisms of action than just ‘knock you out, but don’t necessarily result in better sleep quality’ pharmaceuticals,” says Cooper. “Just getting sleep is only half the battle. We need deep, restful sleep.”

Josh Stanley, director of new business development for CW Hemp, based in Boulder, CO, agrees. “The problem with these drugs is that you’re not sleeping,” he says. “You have to go through your perfect waves of sleep…They rob you of your REM sleep so you don’t go through your proper order of sleep to get to your delta wave. You wake up, you don’t feel refreshed and you have no idea what it is that you dreamt about.”

Natural sleep aids. This is a growing category in the dietary supplement industry. Though most may not frame it in terms of immune health, sleeping properly is the first step to a health immune system. Many of these products such as 5-hydroxytryptophan (5-HTP), Gamma-aminobutyric acid (GABA) and melatonin relate to the chemicals in the brain that control sleep. For example, 5-HTP is a chemical byproduct of the amino acid L-tryptophan, which synthesizes proteins and the neurotransmitter serotonin (1). Serotonin plays a significant role in sleep, mood and pain. In supplements, 5-HTP is derived from a woody African plant called Griffonia simplicifolia.

GABA is an amino acid that acts as an inhibitory neurotransmitter in the central nervous system (CNS) (2). Along with glutamate, its excitatory counterpart, GABA is among the most abundant neurotransmitters in the CNS, particularly in the cerebral cortex where thinking occurs and sensations are interpreted. As an inhibitory neurotransmitter, it prevents neurons from firing. When GABA levels are low — which has been attributed to conditions such as anxiety and insomnia — neurons fire too frequently, creating an over-stimulating effect. Supplementing with GABA in turn creates a calming effect that aids in sound, restful sleep. GABA is derived from glutamine, which is structurally similar to another amino acid called L-theanine notable for its calming effect without sedation (3). For example, L-theanine can work synergistically with caffeine by toning down the stimulating effects and aiding in mental acuity. This can be effectively translated into sleep support in that it calms the mind, making it ideal for the overthinker.

Loud noise can deplete magnesium.

Melatonin is a hormone released by the pineal gland located in the brain which helps regulate the circadian rhythm. According to the University of Maryland Medical Center, melatonin can be an effective tool for people travelling across five or more time zones in order to avoid jet lag (4). Planes are the epicenter for potential illness for a lot of reasons, but discomfort from sleeping in a seated position and the resulting sleep deprivation are a recipe for catching something as soon as you land. Melatonin may curb this.

There are also herbal options to support proper sleep. Kava Kava for example has been a go-to for centuries. “Native to Oceania, Kava Kava root has been used by native populations there for hundreds of years,” explains Dr. Mary Bove, the director of medical education for the firm for Gaia Herbs, based in Brevar, NC. “Kava supports emotional wellbeing, and it promotes a calm mood without inducing sleep. The roots of this herb are also used to promote natural muscle relaxation and support for occasional muscle tension.”

It should be noted that kava should not be consumed habitually or with alcohol or while on medications such as anti-depressants as it can cause long-term damage to the liver. Customers should therefore consult with a physician prior to using the herb.

What many of these sleep support products have in common is that they don’t induce sleep, but simply affect the body in a way that makes better sleep possible, either by enabling greater neurotransmitter production or by easing tension and calming the mind.

Vitamins and Minerals. “Research suggests that vitamins and minerals such as the B group of vitamins, vitamin C, magnesium, zinc, potassium, calcium, and iron are essential for a body to calm the nervous system, in relieving stress and in achieving good sleep,” says Majeed.

Indeed, Shunney recommends a vitamin B complex to her patients who experience stress. “B5 and B6 are known to be particularly important for adrenal health, though I like to make sure they’re getting a B complex including a highly absorbable B12 and methyl folate as well,” she says.

“Magnesium deficiency can cause insomnia, lack of potassium can lead to difficulty staying asleep throughout the night, and vitamin D deficiency has been linked to excessive daytime sleepiness,” says Jordyn Curtis, supply chain manager for Coral LLC, based in Carson City, NV.

Magnesium, a mineral required for more than 700 different enzyme systems, is crucial for both mind and body (5). Unfortunately, when suffering from chronic stress, magnesium is significantly depleted. For example, in her book “The Magnesium Miracle,” Carolyn Dean, MD, ND explains how stimuli such as loud noise can contribute to chronic stress and deplete magnesium (6). “Chronic loud noise in an industrial work setting induced a significant increase in serum magnesium (as magnesium was released from tissues) and significantly increased urinary excretion of magnesium, indicating a magnesium deficiency which lasted 48 hours after exposure,” she writes.

The mineral is also considered to support cognitive health. Dean states in her book that magnesium is a necessary element for the release and uptake of serotonin, but when stress depletes magnesium it affects the release of serotonin, creating an emotional imbalance and the potential for more serious issues such as depression.

Alan Rillorta, director of marketing AIDP, Inc., City of Industry, CA,­­­ describes his firm’s proprietary Magnesium L-Threonate (Magtein). “Animal studies and human clinical trials show that Magtein actively rejuvenates brain neuron cells and can support improved cognitive health and function,” he says. “The brain naturally undergoes gradual structural and functional changes as we age which leads to a natural decline in cognition. The good news is that the adult brain is still capable of a greater degree of plasticity than scientists had previously believed. Our animal studies show that old ‘lazy’ neurons were restored after taking Magtein, leading to an increase in synaptic density.” Improving cognitive function can better fortify a person against stress.

Antioxidants. Cooper also discusses neuroplasticity, specifically as a product of brain-derived neurotrophic factor (BDNF). This is a protein in the brain that helps certain nerve cells survive, grow and mature. BDNF protein is active in the synapses of neurons where cell-to-cell communication occurs. Synapses adapt and change in response to experience (synaptic plasticity) and BDNF regulates this function, crucial to learning and memory. It is found in the parts of the brain that control eating, drinking and body weight (7). BDNF has been shown to degrade as a result of aging, stress and sleep deprivation, says Cooper. “Emerging research on some proprietary lutein ester blends can promote BDNF levels in the brain,” she explains. “Additionally, patent pending, Lutemax 20:20 [by Omniactive Health Technologies, Morristown, NJ], like in Twinlab’s new Blutein products, supports healthy stress response and maintains healthy cortisol levels.”

In the central nervous system, BDNF is known to act upon not only the brain but also the eyes, and lutein is one of three macular carotenoids that also include zeaxanthin and meso-zeaxanthin.  These potent antioxidants are deposited in the eyes’ macula, the area responsible for high visual acuity. While this may not seem relevant, our technological habits and their effect on the eyes has an immediate impact on our ability to sleep. “Blue light is a component of the visible spectrum of light and plays a role in regulating circadian rhythms — our sleep/wake cycles — by inhibiting melatonin production and keeping us alert,” explains Lynda Doyle, MS human nutrition, Sr. VP, global marketing, OmniActive Health Technologies. “Therefore, it is possible that higher exposure to blue light or ‘checking in’ on our digital devices before bedtime may disrupt sleep quality.”

A recent randomized, double-blind, placebo-controlled study by researchers at the University of Georgia, published in Nutritional Neuroscience found that macular carotenoids can reduce stress as well as serum cortisol (8). Fifty-nine subjects between the ages of 18 and 35 were divided into three groups and given either placebo, 13 mg or 27 mg of macular carotenoids per day for 12 months. They were evaluated on blood cortisol, psychological stress ratings, behavioral measures of mood, and symptoms of sub-optimal health at baseline, six months and 12 months. Results showed that after six months of supplementation, the use of macular carotenoids at both doses significantly improved psychological stress, serum cortisol, and measures of emotional and physical health compared to placebo. These improvements were either maintained or improved further at 12 months.

Phytocannabinoids. The endocannabinoid system governs a multitude of functions in the human body including mood, sleep and hormone production. Author John Hicks, MD writes that the endocannabinoid system “interconnects all systems, organs and tissues and responds to changes in the internal and external environment…to keep our bodies functioning at their best by adapting to change” (9). Two types of cannabinoid receptors in the body, CB1 and CB2, are located in every organ system. However, CB1’s prominence in the brain is important for regulating our stress response.

“The CB1 receptor is the most densely distributed receptor type in the human brain,” explains Shunney. “There’s a lot of them in the hypothalamus and the limbic system in general which basically manages our emotional life.”

This is significant because the hypothalamus measures the environment and determines threats, commanding endocrine organs to release stress hormones. “What I see in patients that may use CBD symptomatically to help them get a better night’s sleep, is that over time they will tell me they are often less emotional when a stressful event comes up,” says Shunney.

For Stanley, because the endocannabinoid system is so important and has been neglected for so long, using phytocannabinoids is about achieving balance. “It’s about turning back and connecting our bodies with what we call homeostasis, which is getting our bodies back exactly where they need to be so that they can function properly,” he says.

Adaptogens. Lucille defines adaptogens as a “class of botanicals that help the body adapt to stress and exert a normalizing effect upon the processes.” Particularly effective at supporting adrenal function, adaptogenic herbs are a prominent component of Ayurveda, a form of traditional medicine practiced in India. Important adaptogenic herbs from the Ayurvedic tradition include ashwaghanda and tulsi (holy basil), among others.

Majeed cites a prospective randomized double-blind, placebo-controlled trial in which 64 individuals with a history of chronic stress were administered one 300 mg capsule of ashwaghanda twice daily or placebo for 60 days and assessed for stress by measuring serum-cortisol and taking a standard stress-assessment questionnaire (10). Results showed the experimental group experienced a significant reduction in serum cortisol and scored lower on stress-assessment scales compared to the placebo group.

Some have even evaluated the herb as a potential treatment for anxiety. One study assessed 75 subjects with moderate to severe anxiety who were placed in either a naturopathic care group (NC) or standardized psychotherapy intervention (PT) (11). The NC group consisted of dietary counseling, deep breathing relaxation techniques, a standard multi-vitamin and 300 mg of ashwaghanda. The PT group consisted of psychotherapy, matched deep breathing relaxation techniques and placebo. The intervention lasted a period of 12 weeks and results showed that final Beck Anxiety Inventory scores decreased by 56.5% in the NC group and 30.5% in the PT group, both significant improvements. What’s noteworthy is the significant difference between groups, with the NC group showing more positive results. Although it’s only one trial that requires further examination and replication, this certainly demonstrates ashwaghanda’s potential to mitigate stress in our daily lives so that we improve our health overall.

“Tulsi (Holy Basil) is known for its cortisol-mitigating action in the body,” says Amy Keller, director of education and training, Organic India USA, based in Boulder, CO. “Balanced cortisol levels are associated with healthy energy levels and help the body to maintain restful sleep at appropriate times, while ensuring proper hormonal support during waking hours.”

In the Ayurvedic tradition, the herb is revered as a sacred plant,  adds Majeed. “[Tulsi] is classified as ‘rasayana,’ which means ‘lengthening of lifespan,’” he explains. While we cannot verify this bold claim, research shows the herb has been shown effective in mitigating stress. Majeed cites one controlled trial in particular which explored how supplementation with tulsi would affect individuals with generalized anxiety disorder(GAD) (12). Thirty-five subjects with an average age of 38 years in a hospital-based clinical setting were administered tulsi in a fixed-dose regimen of 500 mg twice daily, after a meal. Measuring psychological rating scale at baseline, 30 days and 60 days, researchers observed that the herb significantly attenuated the subjects’ GAD as well as its correlated stress and depression.

While GAD is a disease state that tulsi is not legally qualified to treat, the research demonstrates the herb’s potential. A different randomized, placebo-controlled trial studying tulsi’s effect on managing general stress provides a picture that is closer to home for most people. In the trial 158 subjects were given either a placebo or 1,200 mg of tulsi per day for six weeks (13). To qualify, subjects had to suffer from at least three of fourteen stress symptoms that included: Quarrelsome behavior with later realization of mistake, frequent feeling of exhaustion or overwork, frequent sleep problems of recent origin and Avoidance of even familiar people.

Subjects self-evaluated the severity of stress symptoms at baseline, two weeks, four weeks and six weeks with results showing that those taking the tulsi had significantly improved scores. Symptoms such as forgetfulness, sexual problems of recent origin, frequent feeling of exhaustion, and frequent sleep problems of recent origin decreased significantly. Total symptom scores were also much lower compared to placebo, with 39% overall improvement of general stress symptoms.

Other herbs and formulations. Many herbal formulas utilize a variety of herbs that work synergistically to support a broader range of functions. Gaia Herbs, for example, has several adrenal health formulations that incorporate adaptogenic herbs and other botanicals along with mushrooms, such as cordyceps. “Modern herbalists use cordyceps to support healthy stamina and physical energy levels,” explains Bove. “It’s considered an immune modulator and adaptogen that promotes overall endocrine health, and it’s also used to support the liver and kidneys. Cordyceps’ diverse functions make it similar to a conductor within the body, supporting the communication between the adrenals and a number of aspects of the immune system.”

A variety of proprietary ingredients also exist targeting aspects of immune health. One ingredient containing Rice Bran Arabinoxylan Compound (PeakImmune4), derived from rice bran modified with the enzyme of shiitake mushroom extract has been proven in clinical research to enhance the activity of the Natural Killer cells, a direct response to our immune health. In terms of sleep and stress, the ingredient also applies.

“During sleep, the immune system releases proteins called cytokines, some of which help promote sleep,” explains Cheatham. “Certain cytokines need to increase when a person has an infection or inflammation, or when one is under stress. Sleep deprivation may decrease production of these protective cytokines. In addition, infection-fighting antibodies and cells are reduced during periods when an individual doesn’t get enough sleep. PeakImmune4 is a dietary supplement proven in extensive scientific research to enhance the activity of protective cytokines.”

Making a Change
Life can get the better of us sometimes, both emotionally and physically. Immune health is definitely influenced by our lifestyles and by emphasizing this to your customers, they will become more cognizant of the stressors in their own lives. Dietary supplements can be the first step to help ease the burden of stress, improve sleep habits and enable us to make the changes our immune system will thank us for.  WF

References

  1. M. Smith. “Sleep Cycle Support.” WholeFoods Magazine. 39(8): 40-42. 2016.
  2. Denver Naturopathic Clinic, “GABA: Gamma-Amino Butyric Acid,” http://www.denvernaturopathic.com/news/GABA.html,accessed July 3, 2017.
  3. “Theanine.” https://examine.com/supplements/theanine/, accessed July 3, 2017.
  4. University of Maryland Medical Center, “Melotonin.” http://www.umm.edu/health/medical/altmed/supplement/melatonin, accessed July 3, 2017.
  5. S. Krawiec. “A Sharp Mind is a Healthy Mind.” WholeFoods Magazine. 39(1): 31-36. 2016.
  6. C. Dean. The Magnesium Miracle (Ballantine Books, New York, NY 2007).
  7. Genetics Home Reference. “BDNF Gene.” https://ghr.nlm.nih.gov/gene/BDNF, accessed July 3, 2017.
  8. N.T. Stringham, et al. “Supplementation with macular carotenoids reduces psychological stress, serum cortisol, and sub-optimal symptoms of physical and emotional health in young adults.” Nutritional Neuroscience. http://www.tandfonline.com/doi/full/10.1080/1028415X.2017.1286445, accessed July 3, 2017.
  9. J. Hicks. The Medicinal Power of Cannabis (Skyhorse Publishing, New York, NY, 2015).
  10. K. Chandrasekhar. “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. 34(3):255-262. 2012.
  11. K. Cooley, et al. “Naturopathic Care for Anxiety: A Randomized Controlled Trial.” PLoS One.4(8). 2009.
  12. D. Bhattacharyya et al. “Controlled programmed trial of Ocimum sanctum leaf on generalized anxiety disorders.” Nepal Medical College Journal. 10(3):176–179. 2008.
  13. R. C. Saxena, et al. “Efficacy of an extract of ocimum tenuiflorum (OciBest) in the management of general stress: A Double-blind, Placebo-controlled Study.” Evidence-based Complementary and Alternative Medicine. 2012.

Sponsored by Daiwa Health Development

Published in WholeFoods Magazine August 2017

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