1. Address inflammation and oxidative stress to restore neurotransmitter balance.
The Impact of Endotoxin LPS on Mental Health
An imbalance in gut flora, chronic body inflammation, stress, and unfavorable environmental factors trigger oxidative stress reactions. These reactions produce endotoxin LPS, which enters the human bloodstream. An excessive concentration of lipopolysaccharide (LPS) in the blood results in inflammation. When the blood-brain barrier becomes compromised, inflammation spreads to the central nervous system, causing disruptions in various neurotransmitters and, subsequently, contributing to mental health issues.
The Features of Inflammation in the Central Nervous System
Central nervous system inflammation is marked by specific attributes. Microglia, which act as the brain's immune cells and clean-up crew, play a pivotal role in determining the occurrence of brain inflammation. When microglia remain persistently "activated" due to factors like stress, the brain's equilibrium is disrupted. Inflammation doesn't only harm neurons it can lead to the demise of numerous nerve cells, but it also disturbs neurotransmitter function.
Based on the above knowledge about inflammation, we need to eliminate or reduce the damage of LPS to the brain, which can be dealt with from the following three aspects:
Step 1: Minimize LPS Entry into the Bloodstream
To achieve this, dietary adjustments and restoration of gut flora are necessary. This will help decrease LPS levels in the intestines and mitigate the body's oxidative stress response and inflammation.
Anti-inflammatory measures: Fish oil, Probiotics
Step 2: Supplement a large amount of antioxidants to regulate the immune system and reduce inflammatory cytokines
When the intestines cannot be repaired in a short period of time, a large amount of antioxidants need to be supplemented to neutralize the body's oxidative stress response, thereby reducing inflammation;
Antioxidant : VC, VE, β-carotene, polyphenols, flavonoids
Step 3: Rebalance neurotransmitters in the central nervous system and reduce symptoms of depression and anxiety
When inflammation cannot be effectively controlled, neurotransmitter nutrients can be supplemented in the short term. Neurotransmitters are chemicals responsible for transmitting messages between neurons, such as dopamine, norepinephrine, and serotonin. A decrease in neurotransmitters affects a person's mood. Today’s antidepressants modulate neurotransmitters
Nutrients that supplement neurotransmitters: 5-HTP, St John’s Wort, B vitamins, B9 and B12
2. Repair of the structure and function of the brain's prefrontal cortex-amygdala-thalamus
Irregularities in the structure and operation of the prefrontal cortex, amygdala, and thalamus are regarded as fundamental factors in the pathophysiology of anxiety disorders.
The brain houses an emotional regulation circuit encompassing the prefrontal cortex, amygdala, hippocampus, hypothalamus, and other interconnected regions. Neuroimaging and studies involving animal models have revealed that structural or functional irregularities in these brain regions are potentially linked to depression and anxiety [17][18].
Studies show that individuals suffering from depression undergo a reduction in specific brain regions. In the case of depressed patients, their hippocampus is notably smaller in comparison to those without depression. Remarkable alterations in hippocampal size become apparent between 8 months and 1 year into a depressive episode. Prolonged periods of depression, without prompt treatment, can result in further reductions in the hippocampal size. Conversely, timely treatment for depression can lead to a recovery in the volume of the hippocampus [19][20].
Pathological anxiety and long-term stress can lead to the reduction of BDNF neurotrophin in the hippocampus and prefrontal cortex, reducing neuroplasticity. The circuits in the prefrontal cortex, amygdala, and hippocampus cannot be properly activated and reorganized according to the environment, resulting in structural degradation. and functional impairment, thereby increasing the risk of mental disorders. [21][22][23]
But the damage is reversible and can be reversed through drug and non-drug treatments. [24]
We can take nutrients to increase BDNF levels, nourish brain nerves, prevent or reverse brain neuron atrophy and increase cell survival, so that brain function and structure can be repaired:
Brain cell: Omega-3, VB, choline, phosphatidylserine, PQQ
BDNF: Omega-3, polyphenols, prebiotics, coffee cherry extract
Cerebral blood flow: Ginkgo leaf extract
I
mportant nutrients for nerve cells. Figure from Oregon State University
3. Provide neuronutrient supplements to restore neurological conditions.
The HPA axis includes the hypothalamus-pituitary gland-adrenal glands and is an important mechanism of the body's response to stress. Under stress, the HPA axis releases the stress hormones cortisol, epinephrine and norepinephrine, leading to sympathetic changes, such as increased heart rate, blood pressure, and breathing. After the emergency has passed, the parasympathetic nervous system intervenes and the body stabilizes to a calm state. Long-term stress and traumatic events cause the nervous system to lose its ability to self-regulate and the nervous system function becomes disordered. Autonomic nerves are composed of sympathetic nerves and parasympathetic nerves. After disorder, these two nerves lose their original normal cooperation. Patients experience various physical symptoms, such as remaining aroused and even experiencing panic attacks. Or parasympathetic nervous excitement leads to fatigue, drowsiness, and depression. [25][26]
There is a lot of research on cortisol secreted in the HPA axis during times of stress.
In a prospective study published by Stanford University in 2015, [27]62 female subjects provided saliva cortisol samples from ages 9 to 14, roughly half of whom had depressed mothers and half of whom had non-depressed mothers, and followed them until age 18. The study found that not all people who experienced a traumatic event (parental divorce, bereavement, love loss, conflict with teachers or classmates...) Only subjects with a high baseline total daily cortisol (AUC) who also experienced trauma were more likely to develop depression.
In the absence of stress and traumatic events, why is cortisol different in humans?
In a clinical study published by Pennsylvania State University in November 2020,[28] 65 subjects underwent blood tests and found that the endotoxin LPS in the blood stimulated the secretion of cortisol. After the human immune system is stimulated by LPS, the secretion of inflammatory cytokines increases, and the secretion of cortisol also increases. Also reflecting significant increases in cortisol concentrations throughout the day.
A 2016 clinical study [29] found that sugary drinks such as soda not only increase visceral fat, but also increase cortisol levels.
Micronutrient deficiencies, such as magnesium deficiency, increase cortisol secretion, and supplementation of the relevant nutrients leads to a significant decrease in cortisol. [30]
We may not be able to control the stress that life causes us, but we can change our diet and supplement with the right nutrition to reduce excessive cortisol, so that overactive and sensitive nerves can return to normal function.
Nutrients that reduces cortisol secretion and restores the nervous system:
Reduce cortisol: Omega-3, VC, polyphenols, magnesium, probiotics
Nerve protection: Omega-3, VB, polyphenols
4, supplement nutrition and restore mitochondrial function in the body
Mitochondria - tiny factories in each of our cells that convert the food we eat and the oxygen we breathe into energy. These energy-related problems can affect the function of both the brain and the rest of the body, result in symptoms of depression, like fatigue and cognitive difficulties . [31]When the energy production process in mitochondria is disturbed, it can impact the growth and repair of nerve cells in the brain, which are fundamental components of the biology underlying depression.[32]
Nutrients that restore mitochondrial function in the body:
Omega-3，VB，alpha-lipoic acid, carnitine, PQQ (pyrroloquinoline quinone) , NAC
5. Supplement probiotics to improve mental health
In recent years, a large number of studies have found that our intestines are closely related to mental health:[33][34][35]
The nerves in our intestines are connected to the brain, so in reality many people have experienced gastrointestinal discomfort caused by stress.
In addition, most of the neurotransmitters are produced in the intestines, including serotonin, dopamine and other neurotransmitters that affect our mood.
An imbalance of intestinal bacteria can allow "bad" bacteria to enter the bloodstream, which may cause inflammation. This can lead to depression/anxiety.
Hence, adding probiotic supplements is a crucial component for preserving and revitalizing mental well-being, with particular consideration for individuals with digestive issues.
Ref:
[17]Electrical fingerprint of the amygdala guides neurofeedback training for stress resilience https://www.nature.com/articles/s41562-018-0484-3?proof=trueJulhttps://io9.gizmodo.com/how-scientists-discovered-the-fear-center-of-the-brai-5848960
[18]Daniela A Espinoza Oyarce, Marnie E Shaw, Khawlah Alateeq, et al. Volumetric brain differences in clinical depression in association with anxiety: a systematic review with meta-analysis, J Psychiatry Neurosci. 2020 Jul 29;45(5):190156.https://doi.org/10.1503/jpn.190156
[19]Xueyi Shen, Lianne M. Reus, Simon R. Cox, Mark J. Adams, David C. Liewald, Mark E. Bastin, Daniel J. Smith, Ian J. Deary, Heather C. Whalley, Andrew M. McIntosh. Subcortical volume and white matter integrity abnormalities in major depressive disorder: findings from UK Biobank imaging data. Scientific Reports, 2017; 7 (1) https://doi.org/10.1038/s41598-017-05507-6
[20]Wei Cheng, Edmund T. Rolls, Jiang Qiu, Wei Liu, Yanqing Tang, Chu-Chung Huang, XinFa Wang, Jie Zhang, Wei Lin, Lirong Zheng, JunCai Pu, Shih-Jen Tsai, Albert C. Yang, Ching-Po Lin, Fei Wang, Peng Xie, Jianfeng Feng. Medial reward and lateral non-reward orbitofrontal cortex circuits change in opposite directions in depression. Brain, 2016; aww255 http://dx.doi.org/10.1093/brain/aww255
[21]Manji HK, Drevets WC, Charney DS. The cellular neurobiology of depression. Nat Med. 2001 May;7(5):541-7. https://doi.org/10.1038/87865. PMID: 11329053.
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[23]Rahman MM, Islam MR, Supti FA, Dhar PS, Shohag S, Ferdous J, Shuvo SK, Akter A, Hossain MS, Sharma R. Exploring the Therapeutic Effect of Neurotrophins and Neuropeptides in Neurodegenerative Diseases: at a Glance. Mol Neurobiol. 2023 Aug;60(8):4206-4231. http://dx.doi.org/10.1007/s12035-023-03328-5 Epub 2023 Apr 13. PMID: 37052791.
[24]Mah L, et al. Can anxiety damage the brain? Current Opinion in Psychiatry： January 2016 - Volume29 - Issue 1 - p 56-63 http://dx.doi.org/10.1097/YCO.0000000000000223
[25]A review of neuroimaging studies in generalized anxiety disorder: "So where do we stand?"
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[27]LeMoult, J., Ordaz, S. J., Kircanski, K., Singh, M. K., & Gotlib, I. H. (2015). Predicting first onset of depression in young girls: Interaction of diurnal cortisol and negative life events. Journal of abnormal psychology, 124(4), 850–859. https://doi.org/10.1037/abn0000087
[28]Davis, Kristin & Engeland, Christopher & Murdock, Kyle. (2020). Ex vivo LPS-stimulated cytokine production is associated with cortisol curves in response to acute psychosocial stress. Psychoneuroendocrinology. 10.1016/j.psyneuen.2020.104863. http://dx.doi.org/10.1016/j.psyneuen.2020.104863
[29]Shearrer, G. E., Daniels, M. J., Toledo-Corral, C. M., Weigensberg, M. J., Spruijt-Metz, D., & Davis, J. N. (2016). Associations among sugar sweetened beverage intake, visceral fat, and cortisol awakening response in minority youth. Physiology & behavior, 167, 188–193. http://dx.doi.org/10.1016/j.physbeh.2016.09.020
[30]Abbasi, Behnood & Kimiagar, Masud & Sadeghniiat, Khosro & Shirazi, Minoo & Hedayati, Mehdi & Rashidkhani, Bahram. (2012). The effect of magnesium supplementation on primary insomnia in elderly: A double-blind placebo-controlled clinical trial. Journal of research in medical sciences : the official journal of Isfahan University of Medical Sciences. 17. 1161-9.https://pubmed.ncbi.nlm.nih.gov/23853635
[31]Rezin GT, Amboni G, Zugno AI, Quevedo J, Streck EL. Mitochondrial dysfunction and psychiatric disorders. Neurochem Res. 2009;34:1021. https://doi.org/10.1007/s11064-008-9865-8
[32] Filler K, Lyon D, Bennett J, McCain N, Elswick R, Lukkahatai N, et al. Association of mitochondrial dysfunction and fatigue: a review of the literature. BBA Clin. 2014;1:12–23 http://dx.doi.org/10.1016/j.bbacli.2014.04.001
[33]The Gut-Brain Axis: How Microbiota and Host Inflammasome Influence Brain Physiology and Pathology. https://www.frontiersin.org/articles/10.3389/fimmu.2020.604179/full
[34]Vagal modulation of responses to mental challenge in posttraumatic stress disorder
T Sahar,A Y Shalev,S W Porges PMID:11297721 https://doi.org/10.1016/S0006-3223(00)01045-3
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