{"id":89176,"date":"2024-06-29T15:42:15","date_gmt":"2024-06-29T15:42:15","guid":{"rendered":"https:\/\/www.stress.org\/?post_type=news&p=89176"},"modified":"2024-06-29T16:08:43","modified_gmt":"2024-06-29T16:08:43","slug":"targeting-ptsds-inflammatory-biomarkers-resolving-inflammation-with-nutrition-based-nitric-oxide-supplementation","status":"publish","type":"news","link":"https:\/\/www.stress.org\/news\/targeting-ptsds-inflammatory-biomarkers-resolving-inflammation-with-nutrition-based-nitric-oxide-supplementation\/","title":{"rendered":"Targeting PTSD\u2019s Inflammatory Biomarkers: Resolving Inflammation with Nutrition-Based Nitric Oxide Supplementation"},"content":{"rendered":"

This article appeared in the Spring 2024 edition of Combat Stress magazine.<\/a><\/p>\n

By Stanford A. Graham, JD and Judy Mikovits, PhD<\/span>\u00a0<\/span><\/p>\n

Introduction<\/span><\/b>\u00a0<\/span><\/p>\n

Neurological dysfunctions are a profound health <\/span>burden among Veterans,<\/span> disrupting and debilitating their lives.<\/span>1<\/span> These dysfunctions are often caused by trauma. Consistent with the variety of ways trauma is experienced, neurological dysfunctions are also a varied complex of biological system dysregulation.<\/span>2<\/span> Unfortunately, even the U.S. Department of Veteran Affairs (VA) describes these neurological conditions within the unhelpful category of \u201cmental health problem[s].\u201d<\/span>3<\/span>\u00a0<\/span><\/p>\n

Fortunately, decades of research are slowly pealing back the layers of these disruptive dysfunctions and their causal complexities. We are learning that neurological dysfunctions are intimately connected with other malfunctioning body systems in a variety of ways. Moreover, recent science is also showing that, at a cellular level, these multi-system dysfunctions also share similar neurological pathways. For example, PTSD is experienced via pathways that are common to substance abuse, diabetes, arthritis, and Alzheimer\u2019s disease.<\/span>4<\/span> Would it surprise you to learn that PTSD symptoms regularly occur contemporaneously with chronic inflammatory symptom conditions such as obesity, type 2 diabetes, insulin resistance,<\/span> chronic pain, sexual dysfunction, and cardiovascular disease?<\/span>4-7<\/span> A 2020 study published in <\/span>Translational Psychiatry<\/span><\/i> emphasized our more complete understanding of neurological dysfunctions this way: \u201cPTSD is no longer classified among anxiety disorders; it is considered a trauma or stressor-related disorder… Because of the marked impact of stressors on the immune system, <\/span>it is not surprising that PTSD is associated with the immune state<\/span><\/i>. <\/span>Increased concentrations of pro-inflammatory factors were observed both within systemic circulation and in the brain in the context of PTSD… highlighting a close link between inflammation, stress, and PTSD.<\/span><\/i>\u201d<\/span>6<\/span> In fact, the more inflammation we experience, the more severe PTSD symptoms become.<\/span>7<\/span>\u00a0<\/span><\/p>\n

\"\"In short, neurological disorders are causally intertwined with immune system dysregulation and its consequent impact on many other biological systems,<\/span>6<\/span>\u00a0including the cardiovascular and nervous systems, the digestive, circulatory,<\/span>8<\/span>\u00a0and the hepatic and endocrine systems, to name a few.<\/span>4<\/span>\u00a0These multi-system malfunctions induce recurring cell-level dysregulation as well, including redox stress, disruption of telomere homeostasis, mitochondrial activity, vitamin D activation, and endothelial nitric oxide (NO) production.<\/span>9,10<\/span>\u00a0These factors cause us to age more quickly, to lose our ability to metabolize our food, negatively affect our ability to think and sleep, and decrease our ability to recover from injury and illness. All these issues weaken the brain and body, making us more susceptible to illness and infection.<\/span>10<\/span>\u00a0<\/span><\/p>\n

What are these \u201cpro-inflammatory factors\u201d that link chronic inflammation, stress, and PTSD?<\/span>\u00a0\u00a0<\/span>They are molecules produced by a dysregulated immune system. They inflame the body, its organs, blood, and tissues, including precise brain regions. They commonly proliferate in groups, including this particular set in PTSD cases: interleukin-1 (IL-1\u03b2), interleukin-6 (IL-6),<\/span>1<\/span>\u00a0tumor necrosis factor (TNF-\u03b1), interferon (INF-<\/span>\u05e5<\/span>), and C-reactive protein (CRP).<\/span>7<\/span>\u00a0This same cytokine group is not only at the heart of PTSD, but at the foundation of XMRV, COVID 19, and Acquired Immune Deficiency\/Dysfunction. Indeed, these cytokines are the biological origins of both body and brain disease and dysregulation.<\/span>5<\/span>\"\"<\/span><\/p>\n

So, the question becomes how can the chronic production of these dangerous cytokines be naturally decreased while simultaneously fortifying and increasing human health? The available data suggest that targeting chronic inflammation \u201cmay serve as a potential therapeutic target for treating neuroimmune disease.\u201d<\/span>4<\/span>\u00a0The good news is that there is both hope and progress. Recent research is exploring ingredient-complex nutraceuticals that act systemically throughout the human body to target these bad-acting molecules while supporting cell health.<\/span>9<\/span>\u00a0<\/span><\/p>\n

Comprehensive research analysis reveals that a deficiency of the amino acid L-arginine (\u201carginine\u201d) is a primary contributor to chronic inflammation and neuroimmune diseases.<\/span>11<\/span>\u00a0So, now you likely have a few questions:\u00a0 What is arginine and how can you safely get what your body needs? What functions does arginine help your body perform to reduce inflammation? What is the relationship between arginine and NO production, and how does NO support vibrant health?<\/span>10<\/span>\u00a0<\/span><\/p>\n

What is Arginine?<\/span><\/b>\u00a0<\/span><\/p>\n

Arginine is a non-essential amino acid, meaning under optimal conditions, the body can produce its own supply. It is derived from body protein breakdown or endogenous de novo arginine production in the kidneys.<\/span>11<\/span>\u00a0When cells are healthy, they also synthesize arginine<\/span>\u00a0from the amino acid L-citrulline (\u201ccitrulline\u201d).<\/span>10<\/span>\u00a0However, when cells are under catabolic stress or trauma, the body\u2019s arginine requirements dramatically increase to help address and resolve injuries and improve biological and neurological functions. Therefore, during injury and healing periods, arginine must be obtained from food intake, making arginine \u201cconditionally\u201d essential.<\/span>11<\/span>\u00a0Arginine is abundant in seeds, nuts, meats, seafood, and soy protein isolate. Yet, despite arginine\u2019s seemingly high availability in non-genetically modified foods, the fluctuating rate at which the human body uses arginine influences its bioavailability and likely deficiency.<\/span>12,13<\/span>\u00a0For example, the small intestines and kidneys collaborate in the whole-body synthesis of arginine.<\/span>14<\/span>\u00a0Consequently, when these organs are dysregulated or injured, arginine deficiency is inevitable. This emphasizes the general need for nutrition-based arginine supplementation.<\/span>15<\/span>\u00a0<\/span>\u00a0<\/span><\/p>\n

Arginine\u2019s Function and Purpose<\/span><\/b>\u00a0<\/span><\/p>\n

Arginine plays a vigorous and versatile role in the human body. It is necessary for cell division, immune system function, ammonia disposal, reparative response to trauma, and wound healing.<\/span>16<\/span>\u00a0It also supports hormone biosynthesis, including stimulating the release of insulin, growth hormone, and endogenous production of vitamin D3.<\/span>9<\/span>\u00a0Arginine is also necessary for T-cell maturation and activation. One of arginine\u2019s most important functions is nitric oxide production. Arginine is the\u00a0<\/span>sole fuel<\/span><\/i>\u00a0specialized cells use to make nitric oxide, often referred to as the \u201cmiracle molecule.\u201d Those specialized cells are called endothelial cells. They compose the interior lining of the entire vascular system.<\/span>17<\/span>\u00a0NO is a primary signaling molecule that facilitates\u00a0<\/span>hundreds of cellular, organ, and biological system functions. This is why arginine deficiencies inevitably result in NO deficiencies. In turn, NO deficiencies invariably lead to immune system dysfunction, blood dysregulation, and the spiraling proliferation of dangerous cytokines and inflammatory diseases, including PTSD.\u00a0\u00a0<\/span>\u00a0<\/span><\/p>\n

PTSD and Global Arginine Bioavailability Ratio<\/span><\/b>\u00a0<\/span><\/p>\n

Recent research shows that solving arginine deficiency and inadequate NO production helps resolve PTSD symptoms and associated inflammation-caused comorbidities.<\/span>10<\/span>\u00a0In 2016, an international research team was the first to measure arginine levels in Veterans with PTSD who had inflammatory levels of IL-1\u03b2, Il-6, TNF\u03b1 and IFN<\/span>\u05e5<\/span>.<\/span>10<\/span>\u00a0Their purpose was to explore the causes of, and possible new therapeutics for, neurological and biological aspects of PTSD.<\/span>7<\/span>\u00a0The team discovered a surprising and direct connection: The inflammatory molecules proliferated when the Veterans had low blood serum levels of arginine. With this observation, the team\u2019s understanding of PTSD expanded \u201cfrom a purely mental illness to an illness with important somatic manifestations\u201d which could \u201clead to novel treatment options for both the psychiatric and somatic aspects of the condition.\u201d<\/span>7<\/span>\u00a0<\/span><\/p>\n

The research team called their diagnostic tool the \u201cglobal arginine bioavailability ratio\u201d (GABR). This ratio identifies the amount of bioavailable arginine in blood serum compared to the combined amounts of two other amino acids, ornithine and citrulline. The research team found that higher levels of bioavailable arginine, with consequent higher levels of bioavailable NO, predictably resulted in lowered PTSD symptom severity. They emphatically concluded: \u201cThe present study provides the first evidence that the global arginine bioavailability [ratio], a marker of NO synthetic capacity in vivo, is decreased in Veterans with PTSD and is negatively associated with markers of inflammation as well as with measures of PTSD symptom severity.\u201d<\/span>7<\/span>\u00a0In short, Veterans with PTSD symptoms were experiencing arginine and NO deficiencies. Thus, increasing both arginine and NO bioavailability decreased inflammatory bio-marker levels and PTSD symptom severity.\u00a0<\/span>\u00a0<\/span><\/p>\n

\"\"Nitric Oxide and its Functions<\/span><\/b>\u00a0<\/span><\/p>\n

As previously stated, endothelial cells are the engine of endothelial NO production. NO creates both good outcomes and prevents bad ones. First, adequate supplies of NO regulate and optimize blood flow, blood viscosity, blood speed, blood oxygenation, vessel flexibility, insulin production, cell cleansing (autophagy), and much more. Additionally, NO maintains the cleanliness of blood vessels, blocking adhesion of blood platelets, lipids, bacteria, and other matter to the inner vascular wall. Hence, NO helps prevent strokes, unwanted blood clotting, hypoxia, and inflammation.<\/span>10<\/span>\u00a0NO deficiency, on the other hand, leads to strokes, atherosclerosis, and the proliferation of oxidative reactive oxygen species (\u201cROS\u201d) throughout the body. In fact, NO deficiency is also the common denominator of many chronic inflammatory diseases, including hypertension, diabetes, aging, heart attack, Alzheimer\u2019s disease, Parkinson\u2019s disease, epilepsy, migraine, and other neurodegenerative diseases.<\/span>10<\/span>\u00a0Maintaining healthy NO production is, therefore, key to sustained functional health. So, how do we prevent NO deficiency?<\/span>\u00a0<\/span><\/p>\n

Mechanisms of Arginine and Nitric Oxide Deficiency<\/span><\/b>\u00a0<\/span><\/p>\n

Arginine deficiency is created in two major ways. First, it results from an unhealthy diet. Second, stress, trauma, and inflammation cause the over-production of arginase, an enzyme that ravenously consumes arginine, resulting in too much ornithine.<\/span>18<\/span>\u00a0\u201cOverly active arginase can reduce the supply of arginine needed for the production of NO, leading to an over-supply of ornithine. Too much\u00a0<\/span>l<\/span>-ornithine can lead to structural problems in the vasculature, neuronal toxicity, and abnormal growth of tumor cells.\u201d<\/span>18\u00a0<\/span>An increase in ROS and inflammatory molecules promote pathological elevations of arginase activity.<\/span>\u00a0<\/span><\/p>\n

Arginine metabolism by arginase, which lowers NO production in PTSD sufferers, is a function of commonly experienced and repeated fact patterns in the lives of Veterans:<\/span>\u00a0<\/span><\/p>\n