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Synergistic Nutrients for Adrenal Support - Part 2

Young Woman Showing Muscle - InterPlexus Blog Synergistic Nutrients for Adrenal Support Part 1


Level Up Your Stress Management Routine This Holiday Season #Beast Mode

It is official - the holiday season is here, and so is the stress that comes with it!

The American Psychological Association performed a survey about holiday stress and discovered that 44% of women report an increased stress level during the holidays, while 31% of men suffer from holiday stress. The survey also determined many people affected by holiday stress often resort to overindulging in food or drinking alcohol to cope with the stress.1

Fortunately, there are healthier options for stress management this holiday season, including nutritional supplements.

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

Specially formulated synergistic blends could not only replace the nutrients depleted by stress but also support stress management, even during the holidays! Truly, adrenal support supplements that nourish the adrenal glands are a fundamental and indispensable part of an effective stress management program at any time of year.

Part 1 of this blog series reviewed many evidence-based options for adrenal support, and we will delve into several more below.

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Evidence-Based Adrenal Support (Continued from Part 1)


Magnesium is required for the optimal function of over 600 enzymes in your body. Magnesium is involved in DNA synthesis, RNA expression, muscle and nerve cell signaling, glucose metabolism, energy production, stress hormone production and release, blood pressure control, and more.2

Magnesium deficiency is common in the modern world and increases the risk of developing many health concerns. The symptoms of magnesium deficiency and stress are surprisingly similar. The most common symptoms of magnesium deficiency include fatigue, irritability, and anxiety.3 Additional symptoms of and conditions associated with a magnesium deficiency include insulin resistance, muscle weakness, increased inflammation, oxidative stress, stomach cramps, high blood pressure, metabolic syndrome, headaches, sleep disorders, and nausea.2,3

Fatigue is a common symptom of magnesium deficiency because all processes in your body that require energy also require magnesium. Magnesium is needed to shuttle adenosine triphosphate (ATP) out of the mitochondria after it is produced. ATP is the energy that powers your cells.4,5 Learn more about energy, magnesium, and ATP HERE.

Excessive stress during the holiday season could increase the need for magnesium in several ways. Extra magnesium is required for the increased demand for cellular energy production and stress hormone synthesis when experiencing holiday stress. Furthermore, holiday stress boosts the need for magnesium because the presence of stress hormones increases the amount of magnesium that leaves the body via urination.6,7

As magnesium leaves the body, a low magnesium level can then reduce the body’s resistance to stress by increasing the secretion of stress hormones, including cortisol. The stress hormones then further deplete magnesium levels, creating a vicious cycle of increased stress and dysfunction.8 When a healthy diet is not enough to maintain an adequate magnesium status, magnesium supplementation tends to be well-tolerated and beneficial.4

So, stress increases the need for magnesium and depletes magnesium, but does supplementation with magnesium decrease stress levels?

Yes! Research confirms magnesium supplementation significantly reduces stress in severely stressed people.8

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Synergistic Stress-Relieving Effects of Magnesium PLUS B-6*

Research also suggests an additional synergistic effect when magnesium is combined with vitamin B6. 8 We already discussed the importance of vitamin B6 for optimal adrenal function in Part 1 of this blog series. But, the combination of vitamin B6 and magnesium enhances the positive effects of magnesium supplementation in severely stressed people.8

The mechanism by which combining magnesium and vitamin B6 leads to reduced stress remains to be defined, but; vitamin B6 may offer direct and indirect effects on stress and the function of the HPA axis. Researchers suspect vitamin B6 may play a role in the entry of magnesium into nerve cells and the distribution of magnesium in the brain.8

They also suggest that vitamin B6 may directly reduce brain noradrenaline levels and modulate gamma-amino butyric acid (GABA) synthesis, resulting in stress relief that complements the effects of magnesium.8 Overall, research shows the combination of vitamin B6 and magnesium could be a powerful component of a comprehensive stress management program.*

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Phosphatidylserine (PS) is an essential phospholipid. Up to 10% of the phospholipid content present in your cell membranes is phosphatidylserine. PS is necessary for proper cell-to-cell recognition and communication. PS is known to enhance cellular metabolism and the transfer of biochemical messages by regulating the function of membrane proteins and influencing the fluidity of the cell membrane. PS regulates cell receptors, enzymes, ion channels, and signaling molecules to directly affect the function of your hormones and intellectual abilities.

According to medical research, supplemental PS also enhances mood, immunity, and the capacity to cope with stress. Many consider supplementing with PS to modulate aspects of the stress response and improve stress adaptation, especially those with circadian rhythm disorders.

One clinical trial determined a supplement with a combination of PS, essential fatty acids, and antioxidants was effective at improving mood, balancing high cortisol levels, and normalizing the daily circadian rhythm in a subset of elderly patients with major depression. Additional clinical studies in middle-aged and younger adults note similar benefits of supplemental PS in reducing perceived stress and optimizing the cortisol response during demanding mental tasks.

Several additional clinical trials confirm supplemental PS modulates the stress response during strenuous exercise training. In an early study, PS effectively blunted the rise of cortisol in response to strenuous exercise in healthy young men. Likewise, PS supplementation decreased the cortisol response to intensive resistance training by 20 percent, reduced muscle soreness, and improved the perception of well-being in young male athletes participating in intensive exercise training.

Another recent study confirmed and elaborated on these results, finding that soy-derived PS lowers resting cortisol levels before exercise, reduces overall cortisol output during physical activity, and increases the testosterone to cortisol ratio after exercise. So, supplementation with PS may improve exercise capacity, antioxidant protection, cognitive function, hormone balance, and overall performance related to athletic training.

Overall, phosphatidylserine supplements appear to effectively improve memory, support adaptability to stress, moderate the perception of stress load and enhance actual performance and recovery in a variety of stressful situations, including intensive exercise training and demanding mental and emotional tasks.9*

For more information about phosphatidylserine, check out our unique blog series about phospholipids and their components HERE!

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Thyroid Support

Hypothyroidism is one of the most common chronic diseases worldwide, and it causes low levels of the thyroid hormones thyroxine (T4) and triiodothyronine (T3).10 Hypothyroidism can lead to adrenal dysfunction. Specifically, hypothyroidism is associated with a reduction in the weight of the adrenal glands, decreased production of cortisol, and an abnormal circadian rhythm.11

Therefore, thyroid support could provide adrenal support when thyroid function is not optimal. Nutrients and botanicals that support optimal thyroid function include L-tyrosine, iodine, Commiphora mukul, L-cysteine, and Ashwagandha.

L-tyrosine is an amino acid that is the precursor of T4, T3, and the adrenal medullary hormones epinephrine and norepinephrine. The tyrosine level in the blood tends to be lower in individuals with hypothyroidism.12 Research shows supplementation with tyrosine does increase thyroid hormone levels.13

The essential trace mineral iodine is required for the synthesis of thyroid hormones. The average adult body contains around 15 to 20 mg of iodine, and most of it is stored in the thyroid gland. Iodine supplementation in individuals who do not consume or absorb enough iodine is beneficial. It is possible to consume too much iodine, so always follow the guidance of your healthcare provider when supplementing with iodine.14

Research suggests the guggulsterones extracted from Commiphora mukul support thyroid function by enhancing the concentration of triiodothyronine (T3) and improving the T3/T4 ratio in the body. Administration of isolated guggulsterones to animal models significantly increases all thyroid function parameters, including:

  • The uptake of iodine by the thyroid
  • The activity of the enzymes involved in the synthesis of thyroid hormones
  • Oxygen uptake by thyroid tissue15

L-cysteine is an amino acid that is required for the production of glutathione (GSH). GSH is critical for optimal thyroid hormone metabolism since it is necessary for the function of an enzyme that converts the T4 thyroid hormone to the active T3 thyroid hormone. Furthermore, GSH affects the uptake of the active T3 thyroid hormone into cells. Animals fed a cysteine-deficient diet suffered from decreased thyroid function and impaired peripheral metabolism of the thyroid hormones.16

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Ashwagandha, which we discussed in Part 1 of this blog series about evidence-based adrenal support, also supports healthy thyroid function.

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.17,18 The withanolides in Ashwagandha are the compounds responsible for the beneficial and relaxing adrenal restorative effects.19 An organic Ashwagandha concentrated extract with at least 5% withanolide content could powerfully support the body during chronic stress, but what does the evidence show?

In a well-designed clinical trial by Chandrasekhar et al., an 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 for 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%20

Several clinical trials and animal studies confirm treatment with Ashwagandha supports thyroid function in those with hypothyroidism.21-24

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It is very common for holiday stress to lead to adrenal dysfunction that could result in new or worsening health concerns. When taken regularly, nutrients, herbs, and other compounds can support stress management and help alleviate the symptoms of chronic stress, including insomnia, depression, anxiety, and fatigue.15

A comprehensive stress management protocol could also reduce the risk of developing other stress-related diseases, including dementia, heart disease, high blood pressure, insulin resistance, obesity, diabetes, and osteoporosis.7 Restoring and optimizing adrenal function is truly a priority for those who wish to level up their health, achieve long-term wellness goals, and enjoy the spirit of the holiday season.*

Hands holding Christmas Gift - InterPlexus Blog

The combination of SeriphosTM, B-KalmPlexusTM, and Flavo PlexCTM could be ideal to support the management of holiday stress. Consider Thyro-DyneTM to also support healthy adrenal function if thyroid function is suboptimal.*

Bioflavonoids and vitamin C are available as a synergistic blend in the popular Flavo PlexCTM dietary supplement.*

B-KalmPlexusTM also offers a synergistic blend that includes magnesium, vitamin B6, vitamin C, and Organic Ashwagandha to support optimal adrenal function.*

SeriphosTM includes the building blocks required to produce phosphatidylserine, which supports a healthy stress response.*

* 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.



Chronic stress is a frequent underlying cause of low nutrient levels and health issues. In fact, according to the World Health Organization (WHO), approximately 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. Fortunately, the consistent use of a synergistic blend of vitamins, minerals, and herbal extracts that nourish the adrenal glands could support a healthy stress response.*


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.*


Phospholipids, including phosphatidylserine and phosphatidylethanolamine, sound like scary toxic chemicals, but every single cell in your body requires phospholipids to function. Phospholipids are present in nearly all food too, so you eat them daily!


Arsenic is the “king of poisons” and the “poison of kings.” Throughout history, Machiavellian villains carried out assassinations for personal gain using this odorless, tasteless, and perfect poison.


  1. APA survey shows Holiday stress putting women's health at risk. American Psychological Association. Accessed September 27, 2022.
  2. Dominguez L, Veronese N, Barbagallo M. Magnesium and Hypertension in Old Age. Nutrients. 2020;13(1):139. doi:10.3390/nu13010139
  3. Pickering G, Mazur A, Trousselard M, et al. Magnesium Status and Stress: The Vicious Circle Concept Revisited. Nutrients. 2020;12(12):3672. doi:10.3390/nu12123672
  4. Barbagallo M, Veronese N, Dominguez LJ. Magnesium in Aging, Health and Diseases. Nutrients. 2021;13(2):463. doi:10.3390/nu13020463
  5. Firetag L. Upgrade your energy this summer! InterPlexus. Published July 8, 2022. Accessed September 27, 2022.
  6. Nayyar M, Yusuf J, Khan MU, et al. K+ and Mg2+ Dyshomeostasis in Acute Hyperadrenergic Stressor States. Am J Med Sci. 2017;353(5):422-424. doi:10.1016/j.amjms.2017.01.001
  7. McCabe D, Lisy K, Lockwood C, et al. 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
  8. Noah L, Pickering G, Mazur A, et al. Impact of magnesium supplementation, in combination with vitamin B6, on stress and magnesium status: secondary data from a randomized controlled trial. Magnes Res. 2020;33(3):45-57. doi:10.1684/mrh.2020.0468
  9. Firetag L. Everything you need to know about the safety and benefits of Phospholipids. InterPlexus. Published September 22, 2022. Accessed September 26, 2022.
  10. Chiovato L, Magri F, Carlé A. Hypothyroidism in Context: Where We've Been and Where We're Going. Adv Ther. 2019;36(Suppl 2):47-58. doi:10.1007/s12325-019-01080-8
  11. Tohei A. Studies on the functional relationship between thyroid, adrenal and gonadal hormones. J Reprod Dev. 2004;50(1):9-20. doi:10.1262/jrd.50.9
  12. Rivlin R, Asper SP. Tyrosine and the thyroid hormones. Am J Med. 1966;40(6):823-827. doi:10.1016/0002-9343(66)90198-7
  13. Tahara Y, Hirota M, Shima K, et al. Primary hypothyroidism in an adult patient with protein-calorie malnutrition: a study of its mechanism and the effect of amino acid deficiency. Metabolism. 1988;37(1):9-14. doi:10.1016/0026-0495(88)90022-4
  14. Knezevic J, Starchl C, Tmava Berisha A, et al. Thyroid-Gut-Axis: How Does the Microbiota Influence Thyroid Function?. Nutrients. 2020;12(6):1769. doi:10.3390/nu12061769
  15. Sarup P, Bala S, Kamboj S. Pharmacology and Phytochemistry of Oleo-Gum Resin of Commiphora wightii (Guggulu). Scientifica (Cairo). 2015;2015:138039. doi:10.1155/2015/138039
  16. Suberville C, Higueret P, Taruoura D, et al. Glutathione deficiency and peripheral metabolism of thyroid hormones during dietary cysteine deprivation in rats. Br J Nutr. 1988;59(3):451-456. doi:10.1079/bjn19880054
  17. 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.
  18. 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
  19. 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.
  20. 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
  21. Sharma AK, Basu I, Singh S. Efficacy and Safety of Ashwagandha Root Extract in Subclinical Hypothyroid Patients: A Double-Blind, Randomized Placebo-Controlled Trial. J Altern Complement Med. 2018;24(3):243-248. doi:10.1089/acm.2017.0183
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  24. Hosny EN, El-Gizawy MM, Sawie HG, et al. Neuroprotective Effect of Ashwagandha Extract against the Neurochemical Changes Induced in Rat Model of Hypothyroidism. J Diet Suppl. 2021;18(1):72-91. doi:10.1080/19390211.2020.1713959

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