Nourishing the HPA Axis with Nutrients
Based on findings from the National Study of Mental Health and Wellbeing 2020 to 2021, 15% of Australians (aged 16 to 85 years) experienced high or very high levels of psychological distress.1 Acute stress activates the hypothalamic-pituitary-adrenal (HPA) axis, with the release of adrenocorticotropic hormone (ACTH) from the pituitary triggering the release of cortisol, epinephrine and norepinephrine from the adrenal glands. This results in alterations in neurotransmitter levels in the brain, including dopamine, serotonin, norepinephrine and epinephrine, gamma-aminobutyric acid (GABA), glutamate, and melatonin.2 Prolonged stress can manifest in symptoms of exhaustion or burnout,3,4 triggered by HPA axis dysregulation. Chronic stress also increases susceptibility to cardiometabolic diseases,5,6 neurodegenerative conditions,7 and immune dysfunction8 due to subsequent changes in underlying neural, endocrine and inflammatory mechanisms.
Replenishing specific nutrient precursors and cofactors that are involved in HPA axis regulation, including those typically depleted by stress, effectively supports the body in times of stress and increased nutritional demand.
Phosphatidylserine
Phosphatidylserine has been shown to normalise stress-induced dysregulation of the HPA axis, by decreasing ACTH and cortisol responses to acute stress.9,10 Two double-blind, randomised, placebo-controlled studies found that supplementation with phosphatidic acid and phosphatidylserine complex (PAS) decreased distress and serum ACTH, serum cortisol and salivary cortisol responses to the trier social stress test. 11,12
Research also suggests that phosphatidylserine supplementation increases dopamine and serotonin turnover,13 which may be useful to increase attention and enhance cognitive function,14 and counteract depression.15 In another double-blind trial, 48 young males were prescribed phosphatidylserine (300 mg/day) or placebo daily for 30 days, then subjected to a mental arithmetic stress test. Treatment was associated with less feelings of stress and better mood, indicating potential benefits from phosphatidylserine in those under academic stress. 16
L-Ornithine
L-ornithine acts as a precursor for GABA,17 and may exert anxiolytic18 and antifatigue effects.19 L-ornithine supplementation also favourably affects the cortisol response, relieving stress, improving sleep quality, and reducing stress-related mood disturbances in individuals living stressful lives.20 In a double-blind, placebo-controlled clinical study, 52 healthy stressed adults were randomised to take either L-ornithine or placebo daily for eight weeks. Results showed that serum cortisol levels and the cortisol/DHEA-S ratio significantly decreased in the L-ornithine group compared to the placebo group. Anger was reduced and perceived sleep quality also improved with treatment. Another study found that supplementation with L-ornithine after alcohol consumption improved various negative feelings including lassitude, fatigue, anger and hostility, improved sleep, and reduced
salivary cortisol levels the following morning.21
Tyrosine
The amino acid tyrosine plays a foundational role in catecholamine synthesis which, in turn, modulates the stress response. Catecholamine synthesis occurs within the adrenal medulla where tyrosine undergoes hydroxylation via tyrosine hydroxylase to form dihydroxyphenylalanine (DOPA). DOPA is then decarboxylated to dopamine before being secreted into the bloodstream, undergoing further hydroxylation to noradrenaline. Noradrenaline may be secreted into circulation or modified to form adrenaline. This occurs via the enzymatic action of phenylethanolamine N-methyltransferase (PNMT), which is stimulated by adrenal glucocorticoids.22 Tyrosine is therefore a key nutrient involved in HPA axis regulation.
A review of 15 trials found that tyrosine supplementation can counteract the cognitive deficits caused by physical and mental stress, as well as improving convergent thinking and improving mood during extreme conditions.23
Vitamin B5 and Vitamin B6
Vitamin B5 is a precursor for coenzyme A (CoA), which plays a vital role in steroidogenesis, including the production of cortisol.24 Animal studies have demonstrated that vitamin B5 directly influences the HPA axis by stimulating adrenal sensitivity to pituitary stimulus (i.e., ACTH) and increasing adrenal steroidogenesis of corticosterone and progesterone.25,26 Deficiency of B5 causes adrenal hypofunction and an inability to respond appropriately to stress.24
Vitamin B6 is required for monoamine (serotonin, dopamine and noradrenaline) synthesis.27 In addition, glutamate is decarboxylated in a P5P-dependent reaction to synthesise GABAError! Bookmark not defined. and is therefore involved in mood regulation.28,29
A meta-analysis of 16 randomised controlled trials found that supplementation with B vitamin complex significantly reduced symptoms of stress in both healthy and at-risk populations (p=0.03). In the at-risk populations, five of eight studies also found a beneficial effect on mood with B vitamin supplementation.30
Nourishing Support with Nutrients
Nourishing the HPA axis and adrenal glands with foundational nutrients can provide the support needed to help clients thrive in the face of stress.
References
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2. Kumar A, Rinwa P, Kaur G, Machawal L. Stress: Neurobiology, consequences and management. J Pharm Bioall Sci. 2013;5(2):91. DOI:10.4103/0975-7406.111818
3. HelpGuide. Burnout prevention and treatment [Internet]. Santa Monica: HelpGuide; 2021 [cited 2022 Jul 18]. Available from: https://www.helpguide.org/articles/stress/burnout-prevention-and-recovery.htm
4. Maslach C, Leiter MP. Understanding the burnout experience: recent research and its implications for psychiatry. World Psychiatry. 2016 Jun;15(2):103-111. DOI: 10.1002/wps.20311
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9. Monteleone P, Maj M, Beinat L, Natale M, Kemali D. Blunting by chronic phosphatidylserine administration of the stress-induced activation of the hypothalamo-pituitary-adrenal axis in healthy men. Eur J Clin Pharmacol. 1992;42(4):385-388. DOI: 10.1007/BF00280123
10. Monteleone P, Beinat L, Tanzillo C, Maj M, Kemali D. Effects of phosphatidylserine on the neuroendocrine response to physical stress in humans. Neuroendocrinology. 1990 Sep;52(3):243-248. DOI: 10.1159/000125593
11. Hellhammer J, Vogt D, Franz N, Freitas U, Rutenberg D. A soy-based phosphatidylserine/ phosphatidic acid complex (PAS) normalizes the stress reactivity of hypothalamus-pituitary-adrenal-axis in chronically stressed male subjects: a randomized, placebo-controlled study. Lipids Health Dis. 2014 Jul;13:121. DOI: 10.1186/1476-511X-13-121
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13. Nizzo MC, Tegos S, Gallamini A, Toffano G, Polleri A, Massarotti M. Brain cortex phospholipids liposomes effects on CSF HVA, 5-HIAA and on prolactin and somatotropin secretion in man. J Neural Transm. 1978;43(2):93-102. DOI: 10.1007/BF01579068
14. Nieoullon A. Dopamine and the regulation of cognition and attention. Prog Neurobiol. 2002 May;67(1):53-83. DOI: 10.1016/s0301-0082(02)00011-4
15. Delgado PL. Depression: the case for a monoamine deficiency. J Clin Psychiatry. 2000;61 Suppl 6:7-11.
16. Benton D, Donohoe RT, Sillance B, Nabb S. The influence of phosphatidylserine supplementation on mood and heart rate when faced with an acute stressor. Nutr Neurosci. 2001;4(3):169-178. DOI: 10.1080/1028415x.2001.11747360
17. Daune G, Seiler N. Interrelationships between ornithine, glutamate, and GABA. II. Consequences of inhibition of GABA-T and ornithine aminotransferase in brain. Neurochem Res. 1988 Jan;13(1):69-75. DOI:10.1007/bf00971857
18. Kurata K, Nagasawa M, Tomonaga S, Aoki M, Morishita K, Denbow DM, et al. Orally administered L-ornithine elevates brain L-ornithine levels and has an anxiolytic-like effect in mice. Nutr Neurosci. 2011 Nov;14(6):243-248. DOI: 10.1179/1476830511Y.0000000018
19. Sugino T, Shirai T, Kajimoto Y, Kajimoto O. L-ornithine supplementation attenuates physical fatigue in healthy volunteers by modulating lipid and amino acid metabolism. Nutr Res. 2008 Nov;28(11):738-743. DOI: 10.1016/j.nutres.2008.08.008
20. Miyake M, Kirisako T, Kokubo T, Miura Y, Morishita K, Okamura H, et al. Randomised controlled trial of the effects of L-ornithine on stress markers and sleep quality in healthy workers. Nutr J. 2014 Jun;13:53. DOI: 10.1186/1475-2891-13-53
21. Kokubo T, Ikeshima E, Kirisako T, Miura Y, Horiuchi M, Tsuda A. A randomized, double-masked, placebo-controlled crossover trial on the effects of L-ornithine on salivary cortisol and feelings of fatigue of flushers the morning after alcohol consumption. BioPsychoSocial Med. 2013;7(1):6. DOI:10.1186/1751-0759-7-6
22. Paravati S, Rosani A, Warrington SJ. Physiology, catecholamines [Internet]. Treasure Island: StatPearls; 2021 [cited 2022 Jul 14]. Available from: https://www.ncbi.nlm.nih.gov/books/NBK507716/
23. Hase A, Jung SE, aan het Rot M. Behavioral and cognitive effects of tyrosine intake in healthy human adults. Pharmacology Biochemistry and Behavior. 2015 Jun;133:1-6. DOI:10.1016/j.pbb.2015.03.008
24. Braun L, Cohen M. Herbs and natural supplements: an evidence-based guide volume 2. 4th ed. Chatswood AU: Churchill Livingstone Elsevier; 2015. pp. 1074-75.
25. Pan L, Jaroenporn S, Yamamoto T, Nagaoka K, Azumano I, Onda M, et al. Effects of pantothenic acid supplement on secretion of steroids by the adrenal cortex in female rats. Reprod Med Biol. 2012 Apr;11(2):101-104. DOI: 10.1007/s12522-011-0113-6
26. Jaroenporn S, Yamamoto T, Itabashi A, Nakamura K, Azumano I, Watanabe G, et al. Effects of pantothenic acid supplementation on adrenal steroid secretion from male rats. Biol Pharm Bull. 2008 Jun;31(6):1205-1208. DOI: 10.1248/bpb.31.1205
27. Sato K. Why is vitamin B6 effective in alleviating the symptoms of autism. Med Hypotheses. 2018 Jun;115:103-106. DOI: 10.1016/j.mehy.2018.04.007
28. Sarawagi A, Soni ND, Patel AB. Glutamate and GABA homeostasis and neurometabolism in major depressive disorder. Front Psychiatry. 2021;12:637863. DOI: 10.3389/fpsyt.2021.637863
29. Krystal JH, Sanacora G, Blumberg H, Anand A, Charney DS, Marek G, et al. Glutamate and GABA systems as targets for novel antidepressant and mood-stabilizing treatments. Mol Psychiatry. 2002;7 Suppl 1:S71-80. DOI: 10.1038/sj.mp.4001021
30. 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