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Synergistic (POWERFUL) Nutrients for Adrenal Support – Part 1

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Level Up Your Stress Management Routine #Beast Mode

We often think of supplements as vitamins and minerals that need to be taken only as needed for potential nutrient deficiencies or inadequacies. However, supplements can offer much more and manifest powerful synergistic benefits that go far beyond simply replacing the vitamins and minerals that could be missing from your diet.

Indeed, it is true that supplements do fill nutrient gaps in your diet, and there are numerous reasons why you might need extra vitamins and minerals. As thoroughly discussed in our previous blog, modern agriculture and food processing methods, dietary restrictions, unhealthy eating habits, life stages that require extra nutrients, certain health conditions, and several lifestyle factors, especially chronic stress, could contribute to nutrient depletion and increase the need for certain nutrients.

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Chronic stress is a frequent underlying cause of both nutrient insufficiencies and health concerns. In fact, according to figures from the World Health Organization (WHO), nearly 450 million people worldwide are affected by stress-related disorders. Research indicates stress could be responsible for an estimated 70% of visits to primary care providers, which is shocking. People who live in countries with higher income levels tend to suffer from more stress-related disorders than those who live in countries with lower income levels. Higher-income modern societies require individuals not only to strive for physical survival but also simultaneously manage job stress, adverse and uncontrollable life events, environmental challenges, financial strain, relationship difficulties, and ongoing time pressure.1

Chronic stress can wreak havoc on your health long before you realize it. Fortunately, consistent use of a potent synergistic blend of vitamins, minerals, and herbal extracts could provide profound health benefits, especially during stressful times.2 Truly, adrenal support supplements that nourish the adrenal glands are a fundamental and indispensable part of an effective stress management program.

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What are adrenal glands and where are the adrenal glands located?

You have two adrenal glands, which are located on each side of your spine, just above your kidneys. Your adrenal glands are part of your endocrine system. The endocrine system includes several glands that secrete hormones to regulate blood pressure, metabolism, blood sugar, reproduction, stress responses, immune responses, and many other essential functions.3

Each adrenal gland has an outer adrenal cortex and an inner adrenal medulla, and these two regions secrete different hormones.3 The adrenal glands are a key component of the specific system the body uses to respond to stress. The overall stress response system in your body is known as the hypothalamic-pituitary-adrenal (HPA) axis, and the HPA axis is a connection between your brain and your adrenal glands. The HPA axis is composed of the hypothalamus and pituitary in your brain and the adrenal glands.4

While responsible for the production of lots of hormones, the adrenal glands are quite small. Each adrenal gland weighs only 3 to 10 grams, which is equivalent to the weight of 3-10 paper clips!5

Stress responce system - InterPlexus Blog Adrenal Support

What does the adrenal gland do?

The adrenal glands produce dozens of different hormones. Cortisol, DHEA, norepinephrine, and adrenaline are the main stress hormones secreted by the adrenal glands. Responding to and recovering from stress are two of the most significant functions performed by the adrenal glands.3

The hormones released by the adrenal glands regulate blood sugar, blood pressure, heart rate, kidney function, immune system function, and many other physiologic processes.4

The purpose of the hormones released by the adrenal glands is homeostasis, or balance, in the body. But, when faced with unrelenting chronic stress, the adrenal glands can falter and release abnormally high or low amounts of hormones. If this occurs, it is possible for the insufficient or excessive hormones released by the adrenal glands to contribute to the development of several health concerns.3

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What is adrenal support?

Adrenal support includes vitamins, minerals, botanical extracts, and other nutrients that support the balanced function of the adrenal glands by supplying the nutrients required by the adrenal glands and optimizing the adrenal response. The nutraceuticals mentioned below are evidence-based options that can support adrenal function and alleviate stress to prevent adrenal fatigue.6

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What is adrenal fatigue?

Chronic stress may lead to a conceptual condition known as adrenal fatigue, which is similar to burnout syndrome.6,7 Adrenal fatigue is not a medical diagnosis but rather a general term for a great number of symptoms that indicate the body could be struggling to cope with stress. The first person to define the term “adrenal fatigue” was a Naturopathic Doctor (ND) and Chiropractor named Dr. James Wilson.7

Screening for the presence of adrenal fatigue requires a panel of saliva tests that assesses adrenal function and its impact on other systems. Chronic stress and sub-optimal adrenal function are associated with many conditions and symptoms including, but not limited to:8

  • Low or high blood pressure
  • Heart disease
  • Diabetes
  • Obesity
  • Insulin resistance
  • Depression
  • Anxiety
  • Skin problems, such as acne or eczema
  • Menstrual problems
  • Diarrhea
  • Constipation
  • Forgetfulness
  • Frequent aches and pains
  • Headaches
  • Lethargy or low energy levels
  • Lack of concentration and focus
  • Osteoporosis
  • Sexual problems
  • Insomnia or sleeping too much
  • Upset stomach
  • The use of alcohol or drugs to relax
  • Unexplained weight loss
  • Abnormal weight gain8

Evidence-Based Adrenal Support

Organic Ashwagandha (Withania somnifera)

Ashwagandha (Withania somnifera) is a botanical medicine prescribed for more than 3000 years in Ayurvedic medicine. Ayurvedic practitioners prescribe Ashwagandha for improving cognitive health, stress management, energy support, anxiety, insomnia, and other health concerns.9,10 The withanolides in Ashwagandha are the compounds responsible for the beneficial and relaxing adrenal restorative effects.11 Based on the traditional use of Ashwagandha, a concentrated organic Ashwagandha extract with at least 5% withanolide content could powerfully support the body during chronic stress.

Ashwagandha superfood powder and root - InterPlexus Blog Adrenal Support

Let's look at the scientific evidence for the benefits of Ashwagandha.

In a well-designed clinical trial by Chandrasekhar et al., Ashwagandha extract administered to individuals under chronic stress significantly reduced their serum cortisol levels compared to the study participants who received a placebo. Study participants that received the Ashwagandha extract also showed substantial improvements on four additional stress assessments.

After only 60 days of supplementation, the Ashwagandha extract:

  • Reduced the “Anxiety and Insomnia” score on the General Health Questionnaire (GHQ-28) by an astounding 69.7%
  • Reduced the “Stress” score on the Depression Anxiety Stress Scale (DASS) by a whopping 64.2%
  • Reduced the “Anxiety” score on the DASS by an impressive 75.6%
  • Significantly reduced the score on the Perceived Stress Scale (PSS) by 44%12

Administering Ashwagandha in animal models also significantly improves cortisol output and depression- and anxiety-associated behavior triggered by social isolation.11

Furthermore, animal studies suggest Ashwagandha offers anti-inflammatory, antioxidant, immunomodulatory, neuro-regenerative, nootropic, neuroprotective, liver-protective, heart-protective, kidney-protective, cholesterol-lowering, anti-bacterial, antifungal, and antiviral benefits. In addition, Ashwagandha has been shown to raise active thyroid hormone levels and could be an antidote for arsenic toxicity.13,14

According to a clinical trial by Wankhede et al., Ashwagandha supplementation in humans is also associated with significant increases in muscle mass and strength, which suggests that Ashwagandha supplementation could be highly valuable when taken during a resistance training program.15

Happy athletic woman exercising with hand weights in a gym - InterPlexus Blog Adrenal Support

Vitamin B-6 (Pyridoxine HCl)

Nutrients are the foundational support for the adrenal glands since they are needed for the production of hormones.16 As a coenzyme involved in over 150 biochemical reactions in your body, vitamin B6 is a fascinating molecule. It is required for the metabolism of carbohydrates, lipids, amino acids, and nucleic acids; and for optimal cellular signaling.17 Recent evidence shows vitamin B6 protects the body from free radicals and other environmental stressors.18

Moreover, research shows a deficiency of vitamin B6 reduces the production of nicotinamide adenine dinucleotide, which is also known as NAD+ or NAD. NAD is required for cellular energy, an optimal circadian rhythm, and resistance to metabolic stress.17,19 In addition, vitamin B6 is necessary for the metabolism of several important neurotransmitters associated with stress, most notably GABA, 5-HTP, serotonin, and dopamine.11

Human brain illustration with hormone biochemical concept - InterPlexus Blog Adrenal Support


Biotin is involved in the regulation of genes that control glucose metabolism, and clinical studies demonstrate improvement in blood sugar control with biotin supplementation. Because of biotin's effects on regulating blood sugar, biotin is most supportive to the adrenal glands when cortisol levels are abnormal due to blood sugar problems or insulin dysregulation, such as insulin resistance.16

A study that included over 7000 adults found that a higher intake of biotin is associated with a lower prevalence of depression, anxiety, and stress.20 An animal study demonstrated increased life span and improved stress resiliency with biotin supplementation. Reports also suggest biotin supplementation improves energy levels.16

Senior Woman Running - InterPlexus Blog Adrenal Support

Vitamin B-5 (Calcium-D-Pantothenate)

In the research literature, pantothenic acid has been shown to raise cortisol levels when needed, improve stress resiliency, improve the acute stress response, and act as a modulating agent for adrenal function. Pantothenic acid is a precursor for the production of acetyl coenzyme A (acetyl-CoA), a compound that is essential for the production of steroid hormones.16 Therefore, the adrenal glands require pantothenic acid to produce several adrenal hormones.16,21

Acetyl-CoA and pantothenic acid are also required to generate ATP and ketones in the mitochondria. ATP and ketones are the primary sources of energy for your body.22 (Learn more about mitochondria and ATP in our previous blog post!) Pantothenic acid, via acetyl-CoA, also contributes to the structure and function of brain cells since acetyl-CoA is involved in the synthesis of cholesterol, amino acids, phospholipids, and fatty acids; and is needed to create multiple neurotransmitters.23

Futuristic mitochondria eukaryotic organelle - InterPlexus Blog Adrenal Support

Zinc (Zinc Ascorbate)

Zinc is an essential trace mineral required for the activity of over 300 crucial enzymes in your body, so a zinc deficiency could significantly impair health.24 Zinc is critical for optimal adrenal function since zinc plays a role in cortisol release by your adrenal glands, and adequate zinc levels stabilize serum cortisol levels over time. Indeed, a zinc deficiency impairs the healthy stress response, exacerbates hormone imbalances, and contributes to the onset of adrenal fatigue.8

In humans, research shows an optimal zinc level after surgery helps maintain a stable cortisol level and prevents the sharp increase in cortisol that tends to occur post-op.16 Research studies on the effect of zinc metabolism in athletes show that alterations in zinc metabolism due to increased zinc excretion and higher stress levels lead to latent fatigue with decreased endurance.8

Zinc is also required to make several neurotransmitters and hormones, including serotonin and melatonin; therefore, a zinc deficiency could affect the circadian rhythm and sleep-wake cycle via mechanisms other than its effect on cortisol production. Prolonged stress depletes zinc concentrations in the blood. Therefore, given that the body has no specialized zinc storage system, regular daily zinc intake is required to prevent the many health problems that could be caused by a zinc deficiency.8

Highlight on chemical element Copper in periodic table of elements

Copper (Copper Citrate)

Similar to zinc, copper is an essential trace element that serves many important functions in the body.8 Copper acts as a cofactor and structural component of many enzymes, including those required for energy production in the mitochondria, as well as serotonin and norepinephrine metabolism.8,25 A copper deficiency can cause many symptoms, including fatigue.8

Wooden bowl filled with whole dried rosmary - InterPlexus blog Adrenal Support

Rosemary (Rosmarinus officinalis)

An animal study that evaluated the effect of rosemary extract on the stress response system, including the HPA axis and brain neurotransmitters, discovered the inhalation of rosemary essential oil lowered the serum corticosterone level and beneficially regulated neurotransmitter levels in the brain to alleviate stress.26

Additional research suggests that rosemary offers anti-inflammatory, analgesic, anti-anxiety, memory boosting, antimicrobial, antioxidant, anti-tumorigenic, and neuroprotective benefits. Historically, rosemary has been used in folk medicine to treat many stress-related health concerns, including nervous agitation, headaches, depression, physical exhaustion, memory concerns, and mental fatigue.27

Chemical formulas and of ascorbic acid vitamin C - InterPlexus Blog Adrenal Support

Vitamin C

Excessive stress leads to the increased use of vitamin C; therefore, increasing your intake of vitamin C during stressful times is necessary to maintain optimal health. Vitamin C acts as an antioxidant in the brain and is a co-factor for the synthesis of adrenaline and other neurotransmitters.1 Vitamin C plays a role in the modulation of dopamine, norepinephrine, serotonin, acetylcholine, and glutamate levels in the brain. A vitamin C deficiency can even directly affect brain function since collagen type IV, which requires vitamin C for synthesis, is essential for healthy nerve cell structure and electrical activity in the brain.28

Vitamin C is also directly required by the adrenal glands and offers a modulatory effect on the HPA axis. Vitamin C is necessary for cortisol synthesis since it is a co-factor for the enzymes present in the adrenal glands. Animal studies suggest that, while vitamin C is required for cortisol production, an optimal vitamin C level reduces the amount of cortisol released due to stress. In fact, vitamin C acts like the brakes on a car with regard to the stress response and can halt an excessive stress response. A vitamin C deficiency can even be an underlying cause of elevated cortisol levels, according to animal studies.28

In clinical trials, supplementation with vitamin C was effective in reducing anxiety, decreasing stress levels, improving recovery from mental stress, boosting mood, and improving blood pressure levels in stressed participants.1,28

Citrus fruits in the basket on the rustic table - InterPlexus Blog Adrenal Support

Organic Citrus Bioflavonoid Complex

Bioflavonoids are a broad class of health-promoting compounds found in numerous plants. Many bioflavonoid-rich plants have been shown to have beneficial effects on adaptation to stress and the stress response.16

Citrus bioflavonoids exert brain-protective (neuroprotective) effects in animal studies. These animal studies also showed bioflavonoid compounds and their metabolites readily cross the blood-brain barrier, which prompted researchers to initiate several clinical trials in humans. The results of these clinical trials demonstrate intake of citrus bioflavonoids improves cognitive function and reduces disease risk in both unhealthy and healthy subjects.29

Specifically, bioflavonoid intake may reduce the risk of depression, anxiety, abnormal blood glucose levels, and abnormal cholesterol levels. Citrus bioflavonoids have also been shown to positively impact the HPA axis via their regulation of the biological clock and circadian rhythms.28

Daily supplementation with a citrus bioflavonoid complex also improves athletic performance. Clinical trials showed that bioflavonoids significantly increase average power by 2.3% to 5%, maximum speed by 3.2%, peak power by 3.7%, and total energy by 2.6% without increasing the maximum heart rate (HR). Furthermore, bioflavonoids may exert other intracellular effects that support mitochondrial function and induce the biogenesis of new mitochondria, which could then produce additional energy for further gains. Learn more about the effects of organic citrus bioflavonoid complex on athletic performance here.24

Accumulating evidence from clinical and epidemiological research suggests that consumption of an organic citrus bioflavonoid complex supports adrenal function, metabolic health, athletic performance, and brain health.24,29*

Woman doing a box squat at the gym - InterPlexus Blog Adrenal Support

It is common for chronic stress to lead to adrenal dysfunction that could result in health concerns. When taken regularly, nutrients and herbs support the optimal function of the HPA axis and help alleviate the symptoms of chronic stress, including insomnia, depression, anxiety, and fatigue.16

A comprehensive stress management protocol could also reduce the risk of developing stress-related diseases, including dementia, heart disease, high blood pressure, insulin resistance, obesity, diabetes, osteoporosis, and other chronic conditions.8 Restoring and optimizing adrenal function is truly a priority for those who wish to level up their health and achieve their long-term wellness goals.*

Organic Ashwagandha, Vitamin B5, Vitamin B6, Biotin, Zinc, Copper, Rosemary Extract & Organic Bioflavonoid Complex, are available as a synergistic blend in the popular AdaptTM dietary supplement.

Bioflavonoids and vitamin C are available in Flavo PlexCTM, a formulation that supports healthy immunity and optimal adrenal function.*

Stay tuned for more information about evidence-based adrenal support in our next blog, which will be posted just in time to help you manage holiday stress!

* This statement has not been evaluated by the Food and Drug Administration. This product is not intended to diagnose, treat, cure or prevent any disease.



The common cold is the most frequent human illness. Genetics, stress, smoking, nutrient deficiencies, and strenuous physical training can increase the risk of catching a cold. Modern research now confirms that supplemental vitamins, minerals, botanicals, and other natural remedies can decrease the severity and duration of the common cold.*


It’s that time of year! Are you suffering from a runny nose, itchy eyes, sneezing, nasal congestion, or other symptoms of seasonal allergies? If so, you are not alone! Over 40% of the US population has allergies. According to the National Health and Nutrition Examination Survey (NHANES), 44.6% of the US population has detectable Immunoglobulin E (IgE) antibodies in their blood, and we know IgE antibodies play a central role in instigating the symptoms associated with allergies...


While many of us know that daily supplementation with probiotics supports health, research is now beginning to teach us about the fascinating world of POSTbiotics!


Think you don’t need supplements? Think again! You may want to reconsider your thoughts about supplements to improve your health and well-being since your body requires a certain amount of each of the essential nutrients daily to function optimally!


  1. McCabe D, Lisy K, Lockwood C, Colbeck M. The impact of essential fatty acid, B vitamins, vitamin C, magnesium and zinc supplementation on stress levels in women: a systematic review. JBI Database System Rev Implement Rep. 2017;15(2):402-453. doi:10.11124/JBISRIR-2016-002965
  2. Speers AB, Cabey KA, Soumyanath A, et al. Effects of Withania somnifera (Ashwagandha) on Stress and the Stress- Related Neuropsychiatric Disorders Anxiety, Depression, and Insomnia. Curr Neuropharmacol. 2021;19(9):1468-1495. doi:10.2174/1570159X19666210712151556
  3. Adrenal glands. Johns Hopkins Medicine. Published August 8, 2021. Accessed August 3, 2022.
  4. Kanczkowski W, Sue M, Bornstein SR. The adrenal gland microenvironment in health, disease and during regeneration. Hormones (Athens). 2017;16(3):251-265. doi:10.14310/horm.2002.1744
  5. Lam KY, Chan AC, Lo CY. Morphological analysis of adrenal glands: a prospective analysis. Endocr Pathol. 2001;12(1):33-38. doi:10.1385/ep:12:1:33
  6. Feldt M. Neurological health – stress and adrenal support. Fullscript. Published May 27, 2022. Accessed August 3, 2022.
  7. Sjörs Dahlman A, Jonsdottir IH, Hansson C. The hypothalamo-pituitary-adrenal axis and the autonomic nervous system in burnout. Handb Clin Neurol. 2021;182:83-94. doi:10.1016/B978-0-12-819973-2.00006-X
  8. Trimnell A, Canar L, Firetag L. CHRONIC STRESS - The Physical & Emotional Tolls. July 2020. Accessed August 4, 2022.
  9. Sarris J, McIntyre E, Camfield DA. Plant-based medicines for anxiety disorders, part 2: a review of clinical studies with supporting preclinical evidence. CNS Drugs. 2013 Apr; 27(4): 301-19. doi:10.1007/s40263-013-0059-9.
  10. Dutta R, Khalil R, Green R, et al. Withania Somnifera (Ashwagandha) and Withaferin A: Potential in Integrative Oncology. Int J Mol Sci. 2019;20(21):5310. doi:10.3390/ijms20215310
  11. Head KA, Kelly GS. Nutrients and botanicals for treatment of stress: adrenal fatigue, neurotransmitter imbalance, anxiety, and restless sleep. Altern Med Rev. 2009 Jun;14(2):114-40.
  12. 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(3):255-262. doi:10.4103/0253-7176.106022
  13. Saleem S, Muhammad G, Hussain MA, et al. Withania somnifera L.: Insights into the phytochemical profile, therapeutic potential, clinical trials, and future prospective. Iran J Basic Med Sci. 2020;23(12):1501-1526.
  14. Panda S, Kar A. Changes in thyroid hormone concentrations after administration of ashwagandha root extract to adult male mice. J Pharm Pharmacol. 1998 Sep;50(9):1065-8. doi:10.1111/j.2042-7158.1998.tb06923.x
  15. Wankhede S, Langade D, Joshi K, et al. Examining the effect of Withania somnifera supplementation on muscle strength and recovery: a randomized controlled trial. J Int Soc Sports Nutr. 2015;12:43. doi:10.1186/s12970-015-0104-9
  16. Buesing, A Foundational Approach to Adrenal Restoration. Chronobiology. 2015;3(20):1-3,6. Accessed August 8, 2022.
  17. Stach K, Stach W, Augoff K. Vitamin B6 in Health and Disease. Nutrients. 2021;13(9):3229. doi:10.3390/nu13093229
  18. Mooney S, Leuendorf JE, Hendrickson C, et al. Vitamin B6: a long known compound of surprising complexity. Molecules. 2009;14(1):329-351. doi:10.3390/molecules14010329
  19. Groth B, Venkatakrishnan P, Lin SJ. NAD+ Metabolism, Metabolic Stress, and Infection. Front Mol Biosci. 2021;8:686412. doi:10.3389/fmolb.2021.686412
  20. Mahdavifar B, Hosseinzadeh M, Salehi-Abargouei A, et al. Dietary intake of B vitamins and their association with depression, anxiety, and stress symptoms: A cross-sectional, population-based survey. J Affect Disord. 2021;288:92-98. doi:10.1016/j.jad.2021.03.055
  21. Pan L, Jaroenporn S, Yamamoto T, et al. Effects of pantothenic acid supplement on secretion of steroids by the adrenal cortex in female rats. Reprod Med Biol. 2011;11(2):101-104. doi:10.1007/s12522-011-0113-6
  22. Pietrocola F, Galluzzi L, Bravo-San Pedro JM, et al. Acetyl coenzyme A: a central metabolite and second messenger. Cell Metab. 2015;21(6):805-821. doi:10.1016/j.cmet.2015.05.014
  23. Kennedy DO. B Vitamins and the Brain: Mechanisms, Dose and Efficacy--A Review. Nutrients. 2016;8(2):68. doi:10.3390/nu8020068
  24. Summertime Nutrition for Men. Interplexus. June 2022. Accessed August 10, 2022.
  25. Lutsenko S, Washington-Hughes C, Ralle M, et al. Copper and the brain noradrenergic system. J Biol Inorg Chem. 2019;24(8):1179-1188. doi:10.1007/s00775-019-01737-3
  26. Villareal MO, Ikeya A, Sasaki K, et al. Anti-stress and neuronal cell differentiation induction effects of Rosmarinus officinalis L. essential oil. BMC Complement Altern Med. 2017;17(1):549. doi:10.1186/s12906-017-2060-1
  27. Ghasemzadeh Rahbardar M, Hosseinzadeh H. Therapeutic effects of rosemary (Rosmarinus officinalis) and its active constituents on nervous system disorders. Iran J Basic Med Sci. 2020;23(9):1100-1112. doi:10.22038/ijbms.2020.45269.10541
  28. Moritz B, Schmitz AE, Rodrigues ALS, et al. The role of vitamin C in stress-related disorders. J Nutr Biochem. 2020;85:108459. doi:10.1016/j.jnutbio.2020.108459
  29. Matsuzaki K, Nakajima A, Guo Y, et al. A Narrative Review of the Effects of Citrus Peels and Extracts on Human Brain Health and Metabolism. Nutrients. 2022;14(9):1847. doi:10.3390/nu14091847

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