BioGPS - The Kynurenine Pathway

Tryptophan Metabolites Blood Test

Through the Kynurenine Pathway, tryptophan contributes to immune modulation and the production of NAD+, a coenzyme essential for cellular energy production and longevity.

Tryptophan Metabolites Blood Test

Tryptophan, an essential amino acid, plays a multifaceted role in the regulation of various physiological processes, including protein synthesis, neurotransmitter production, immune function, and mood regulation. Tryptophan is involved in promoting healthy aging through the following mechanisms:

  1. Serotonin Production: Tryptophan is a precursor for serotonin, a neurotransmitter involved in mood regulation, sleep-wake cycles, appetite control, and cognitive function. Adequate serotonin levels are essential for maintaining emotional well-being and overall quality of life, factors that contribute to healthy aging.

  2. Melatonin Synthesis: Tryptophan is also a precursor for melatonin, a hormone that regulates the sleep-wake cycle and has antioxidant properties. Melatonin levels decline with age, and disturbances in circadian rhythms are associated with aging-related conditions such as insomnia and cognitive decline. Supplemental melatonin has been studied for its potential anti-aging effects and its ability to improve sleep quality and cognitive function in older adults.

  3. Immune Function: Tryptophan metabolism through the kynurenine pathway (KP) has immunomodulatory effects and plays a role in regulating immune responses. Dysregulation of the KP has been implicated in aging-related inflammation and immune dysfunction. Balancing tryptophan metabolism within the KP may contribute to healthy immune aging and longevity.

  4. Antioxidant Properties: Tryptophan metabolites, such as serotonin and melatonin, possess antioxidant properties and helps mitigate oxidative stress, which is a hallmark of aging and contributes to age-related cellular damage and degenerative diseases. By scavenging free radicals and reducing oxidative damage, tryptophan and its derivatives promote longevity and healthy aging.

  5. Gut Microbiota: Tryptophan is metabolized by gut microbiota into bioactive metabolites that influence host physiology and metabolism. The gut-brain axis, which involves bidirectional communication between the gut microbiota and the central nervous system, plays a role in aging-related processes, including cognitive decline and neurodegeneration. Tryptophan metabolism by gut bacteria impacts longevity by modulating host metabolism, inflammation, and brain function.

 

9 Tryptophan Metabolites tested: Tryptophan, Kynurenine, Tryptophan/Kynurenine Ratio, Kynurenic Acid, Quinolinic Acid, NAD+/NADH, 5-Hydroxytryptophan (5-HTP), Serotonin, Melatonin

Price: $235.00

Price includes convenient home collection kit for sample collection from the comfort of your home

The Kynurenine Pathway (KP)

The Kynurenine Pathway (KP) is the central route for the metabolism of the amino acid tryptophan. It is one of the most researched pathways in the context of both the immune and nervous systems due to its implication in various disease processes.

  1. Starting Point – Tryptophan: The amino acid tryptophan, which we primarily get from our diet, serves as the precursor for the kynurenine pathway. Only a small portion of dietary tryptophan goes to produce serotonin, while the majority enters the KP.
  2. Initiation of the Pathway: The conversion of tryptophan to kynurenine is the first and rate-limiting step. This conversion is catalyzed by enzymes such as indoleamine 2,3-dioxygenase (IDO) and tryptophan 2,3-dioxygenase (TDO). The activity of these enzymes can be influenced by various factors, including inflammatory cytokines.
    1. TDO is mostly liver-specific and is regulated by tryptophan levels, while IDO is found in various tissues and can be induced by inflammatory signals, particularly cytokines.
  3. Kynurenine Metabolites: Once kynurenine is produced, it can be further metabolized to produce various biologically active compounds, including kynurenic acid, anthranilic acid, 3-hydroxykynurenine, and quinolinic acid. Each of these metabolites has its own set of effects, and their balance can influence neurological and immune functions. For example, kynurenic acid is neuroprotective, while quinolinic acid can be neurotoxic.
    1. Bioactive Metabolites:
      1. Kynurenine: The primary metabolite which can be further metabolized into other bioactive compounds.
      2. Kynurenic Acid: Exhibits neuroprotective effects. It antagonizes the N-methyl-D-aspartate (NMDA) receptor and blocks the α7 nicotinic acetylcholine receptor.
      3. Quinolinic Acid: Acts as an agonist at the NMDA receptor, leading to excitotoxicity and potentially promoting neuroinflammation.
  4. Inflammation and Immune Modulation: Some metabolites of the KP, like kynurenic acid, can act as anti-inflammatory agents by modulating the immune response, including reducing the activity of immune cells. Conversely, other metabolites, such as quinolinic acid, can exacerbate inflammation, promote oxidative stress, and have neurotoxic effects. A shift towards the production of quinolinic acid over kynurenic acid in certain conditions can heighten neuroinflammatory responses and is observed in some neurodegenerative diseases.
  5. Neurotransmitter Synthesis: The KP is involved in the synthesis of the neurotransmitter serotonin and, indirectly, in the production of the neurotransmitter NAD (nicotinamide adenine dinucleotide), a crucial molecule for various cellular processes.
  6. Clinical Significance: Dysregulation of the KP has been linked to various conditions such as depression, anxiety, schizophrenia, and neurodegenerative diseases. The pathway is also intricately linked with the immune system and can be influenced by inflammatory processes.
  7. Role in Immune Regulation: The KP plays a role in immune system modulation. For example, activation of IDO and subsequent metabolism of tryptophan to kynurenine can suppress immune responses, which has implications in cancer, autoimmunity, and infectious diseases.
  8. Therapeutic Targeting: Given the KP’s involvement in numerous diseases, it has been proposed as a therapeutic target. Drugs that modulate the activity of the pathway’s enzymes or the effects of its metabolites might offer therapeutic benefits for a range of conditions.

The Kynurenine Pathway (KP) And NAD+

The kynurenine pathway (KP) is a critical route for the catabolism of the essential amino acid tryptophan, leading to the production of several metabolites, including nicotinamide adenine dinucleotide (NAD+), a vital coenzyme in cellular energy metabolism.

Here’s how the KP is involved in NAD+ synthesis:

  1. Tryptophan Catabolism: The KP begins with the oxidation of tryptophan, catalyzed by either indoleamine 2,3-dioxygenase (IDO) or tryptophan 2,3-dioxygenase (TDO), producing N-formylkynurenine. N-formylkynurenine is then converted to kynurenine.

  2. Formation of Kynurenine Metabolites: Kynurenine can be metabolized through several pathways, leading to the production of key intermediates such as 3-hydroxykynurenine, anthranilic acid, and kynurenic acid. The pathway splits into several branches, but for NAD+ synthesis, the most relevant branch involves the conversion of kynurenine to 3-hydroxykynurenine by kynurenine monooxygenase (KMO).

  3. Conversion to 3-Hydroxyanthranilic Acid: 3-Hydroxykynurenine is further converted to 3-hydroxyanthranilic acid by the enzyme kynureninase.

  4. Formation of Quinolinic Acid: 3-Hydroxyanthranilic acid is converted to quinolinic acid by the enzyme 3-hydroxyanthranilate 3,4-dioxygenase. Quinolinic acid is a crucial intermediate in the KP and plays a direct role in NAD+ synthesis.

  5. Synthesis of NAD+: Quinolinic acid is converted to nicotinic acid mononucleotide (NAMN) by the enzyme quinolinate phosphoribosyltransferase (QPRT). NAMN is subsequently converted through a series of enzymatic steps to NAD+, involving enzymes such as nicotinic acid mononucleotide adenylyltransferase (NMNAT) and NAD+ synthetase.

Role of NAD+ in Cellular Function

NAD+ is an essential coenzyme involved in numerous cellular processes, including:

  • Redox Reactions: NAD+ functions as an electron carrier in redox reactions, essential for ATP production through glycolysis, the citric acid cycle, and oxidative phosphorylation.
  • DNA Repair: NAD+ is a substrate for poly(ADP-ribose) polymerases (PARPs), enzymes involved in DNA repair and genomic stability.
  • Gene Expression: NAD+ is a substrate for sirtuins, a family of NAD+-dependent deacetylases that regulate gene expression, metabolism, and aging.
  • Cell Signaling: NAD+ and its metabolites play roles in cell signaling pathways, including those regulating immune responses and inflammation.

Impact of KP Dysregulation

Dysregulation of the KP affects NAD+ synthesis and contribute to various pathological conditions, including:

  • Neurodegenerative Diseases: Imbalances in KP metabolites, such as increased quinolinic acid, leads to neurotoxicity and are implicated in disorders like Alzheimer’s disease and Huntington’s disease.
  • Immune Dysfunction: Chronic activation of the KP, often driven by inflammation and immune responses, alter NAD+ metabolism and contribute to immune dysregulation.
  • Metabolic Disorders: Alterations in NAD+ levels affect metabolic pathways and contribute to conditions such as diabetes and obesity.

 

Understanding the kynurenine pathway’s role in NAD+ synthesis is crucial for developing therapeutic strategies aimed at modulating this pathway to treat various diseases and promote healthy aging.

The Kynurenine Pathway (KP), Serotonin Synthesis, Inflammation, and Energy Production

The interplay between the Kynurenine Pathway (KP), Serotonin Synthesis, Inflammation, and Energy Production is complex, and current understanding suggests that disturbances in these processes can have profound implications for health, including neuropsychiatric disorders, fatigue, and other systemic effects. Let’s dive deeper into their interconnectedness:

  1. Tryptophan Metabolism: Both the KP and serotonin synthesis begin with the amino acid tryptophan. Depending on various factors, tryptophan can either be converted into serotonin or metabolized down the KP.
  2. Inflammation and KP Activation: Inflammation, especially chronic inflammation, has been shown to stimulate the KP. Inflammatory cytokines, such as interferon-gamma (IFN-γ), upregulate the enzyme indoleamine 2,3-dioxygenase (IDO), which converts tryptophan to kynurenine. As a result, more tryptophan is shunted towards the KP, leading to decreased serotonin synthesis.
  3. Effects on Neurotransmission: Reduced availability of tryptophan for serotonin synthesis can lead to decreased levels of serotonin, a neurotransmitter associated with mood regulation, appetite, and sleep. Lower serotonin levels have been implicated in depression, anxiety, and other neuropsychiatric disorders.
  4. KP Metabolites and Neuroinflammation: Some metabolites produced in the KP, especially quinolinic acid, exert neurotoxic effects and contribute to neuroinflammation. Quinolinic acid is an agonist of the NMDA receptor, and its overstimulation can lead to excitotoxicity, potentially damaging neurons.
  5. Energy Production and Fatigue: Tryptophan and its metabolites, especially those down the KP, influence energy production. Kynurenine and its derivatives can modulate mitochondrial function, which is central to cellular energy production. Disturbances in the KP, therefore, contribute to fatigue or reduced energy production.
  6. Therapeutic Implications: Recognizing the role of inflammation in shifting tryptophan metabolism can pave the way for therapeutic strategies. For instance, addressing underlying inflammation might help in conditions characterized by fatigue, mood disturbances, or altered energy metabolism.

In Summary: The balance of tryptophan metabolism, involving the KP and serotonin synthesis, is crucial for both brain function and systemic health. Inflammation can shift this balance, potentially leading to neuroinflammation, altered neurotransmission, and disturbances in energy production.

Test Details

The kynurenine pathway (KP) plays a significant role in longevity due to its influence on various physiological processes, including immune regulation, redox balance, and energy metabolism.

Here are some key points highlighting the importance of the KP in longevity:

  1. NAD+ Synthesis and Energy Metabolism
    1. NAD+ Production: One of the crucial end products of the KP is nicotinamide adenine dinucleotide (NAD+), an essential coenzyme involved in cellular energy production through glycolysis, the citric acid cycle, and oxidative phosphorylation.
    2. Energy Balance: Adequate levels of NAD+ are vital for maintaining mitochondrial function and energy homeostasis. Declines in NAD+ levels are associated with aging and age-related metabolic decline. Boosting NAD+ levels through KP modulation can enhance mitochondrial function and energy metabolism, promoting longevity.
  2. Immune Regulation and Inflammation
    1. Modulation of Immune Response: The KP is activated during immune responses, particularly through the enzyme indoleamine 2,3-dioxygenase (IDO), which is induced by pro-inflammatory cytokines. This pathway helps regulate immune responses and maintain immune tolerance.
    2. Chronic Inflammation: Persistent activation of the KP, especially in chronic inflammatory conditions, can lead to sustained production of pro-inflammatory metabolites like quinolinic acid. Chronic inflammation is a hallmark of aging (inflammaging) and contributes to various age-related diseases. Proper regulation of the KP can help mitigate chronic inflammation and its detrimental effects on aging.
  3. Oxidative Stress and Neuroprotection
    1. Antioxidant Defense: Some KP metabolites, such as kynurenic acid, possess antioxidant properties and can protect against oxidative stress. Oxidative stress damages cellular components and is a major factor in aging and neurodegenerative diseases.
    2. Neuroprotection: Kynurenic acid acts as an antagonist at NMDA receptors, protecting neurons from excitotoxicity. Conversely, quinolinic acid is neurotoxic and can contribute to neurodegeneration. Balancing these metabolites is crucial for neuroprotection and cognitive health, which are important for healthy aging.
  4. Regulation of Tryptophan Availability
    1. Serotonin and Melatonin Synthesis: Tryptophan is a precursor for serotonin and melatonin, neurotransmitters involved in mood regulation and circadian rhythm. Imbalances in tryptophan metabolism can affect mental health and sleep, which are critical for overall well-being and longevity.
  5. Cellular Senescence and Aging
    1. Senescence and Aging: Dysregulation of the KP has been linked to cellular senescence, a state of irreversible cell cycle arrest that contributes to aging and age-related diseases. Modulating the KP can influence cellular senescence pathways, potentially delaying the onset of age-related conditions.
  6. Conclusion: The kynurenine pathway’s regulation of NAD+ synthesis, immune response, oxidative stress, and neuroprotection positions it as a critical player in the aging process and longevity. By influencing these fundamental biological processes, the KP offers potential targets for therapeutic interventions aimed at extending healthspan and delaying the onset of age-related diseases. Understanding and modulating the KP can thus be a valuable strategy in promoting healthy aging and longevity.

9 Analytes Tested:

  1. Tryptophan
  2. Kynurenine
  3. Tryptophan/Kynurenine Ratio
  4. Kynurenic Acid
  5. Quinolinic Acid
  6. 5-Hydroxytryptophan (5-HTP)
  7. Serotonin
  8. Melatonin
  9. NAD+/NADH

Tryptophan is an essential amino acid crucial for various physiological functions, impacting health, well-being, and longevity. Since the body cannot synthesize tryptophan, it must be obtained from dietary sources such as poultry, dairy products, nuts, seeds, and legumes.

Here are the key reasons why tryptophan is important:
  1. Precursor for Neurotransmitters and Hormones:
    1. Serotonin: Tryptophan is the precursor for serotonin, a neurotransmitter that regulates mood, sleep, appetite, and cognitive functions. Adequate serotonin levels are essential for mental health, and imbalances can lead to mood disorders such as depression and anxiety.
    2. Melatonin: Serotonin is further converted into melatonin, a hormone that regulates the sleep-wake cycle and has antioxidant properties. Proper melatonin levels are crucial for sleep quality, circadian rhythm regulation, and overall well-being.
  2. NAD+ Synthesis and Energy Metabolism:
    1. Kynurenine Pathway: Tryptophan is metabolized through the kynurenine pathway (KP), leading to the production of nicotinamide adenine dinucleotide (NAD+), a vital coenzyme in cellular energy metabolism. NAD+ is essential for ATP production, DNA repair, and the activation of sirtuins, proteins involved in aging and longevity.
  3. Immune Regulation:
    1. Modulation of Immune Responses: Metabolites from the kynurenine pathway, such as kynurenine and its derivatives, play roles in modulating immune responses and maintaining immune homeostasis. Proper regulation of these metabolites helps prevent chronic inflammation and autoimmune diseases.
  4. Cognitive Function and Neuroprotection:
    1. Neurotransmitter Balance: Tryptophan and its metabolites influence the balance of neurotransmitters, which are critical for cognitive functions such as memory, learning, and attention.
    2. Neuroprotection: Kynurenic acid, a metabolite of tryptophan, has neuroprotective properties that help protect neurons from excitotoxicity and oxidative stress, factors involved in neurodegenerative diseases.
  5. Gut Health:
    1. Microbiota Interaction: Tryptophan is metabolized by gut microbiota into bioactive compounds that influence gut health and systemic inflammation. A healthy gut microbiota composition is essential for overall health and can impact metabolic and immune functions.
  6. Protein Synthesis:
    1. Building Block of Proteins: As an amino acid, tryptophan is a fundamental building block of proteins. It is involved in the synthesis of various structural and functional proteins necessary for growth, repair, and maintenance of body tissues.
  7. Mental Health and Well-Being:
    1. Mood Regulation: Adequate tryptophan intake is essential for maintaining serotonin levels, which are crucial for mood stabilization. Low tryptophan levels can lead to mood disturbances and are associated with conditions such as depression.
    2. Stress Response: Tryptophan and its metabolites influence the body’s response to stress, helping to maintain mental resilience and overall psychological health.

Kynurenine is a crucial metabolite in the kynurenine pathway (KP) of tryptophan metabolism and plays an essential role in several physiological processes that impact health, disease, and longevity. The significance of kynurenine extends across multiple domains, including immune regulation, neuroprotection, energy metabolism, and mental health.

Key Roles and Importance of Kynurenine:

  1. Immune Regulation:
    1. Modulation of Immune Responses: Kynurenine has immunomodulatory properties that help regulate the immune system. It influences the balance between pro-inflammatory and anti-inflammatory responses, contributing to immune homeostasis.
    2. T-cell Regulation: Kynurenine induces the differentiation of regulatory T cells (Tregs), which help maintain immune tolerance and prevent autoimmune reactions. This is crucial for preventing chronic inflammation and autoimmune diseases.
  2. Neuroprotection:
    1. Neuroprotective Metabolites: Kynurenine is a precursor to kynurenic acid, a neuroprotective agent that acts as an antagonist at NMDA and alpha-7 nicotinic acetylcholine receptors. This helps protect neurons from excitotoxicity and oxidative stress.
    2. Balancing Neurotoxic Effects: Kynurenine pathway also produces quinolinic acid, a neurotoxic metabolite. The balance between neuroprotective kynurenic acid and neurotoxic quinolinic acid is critical for maintaining neuronal health and preventing neurodegenerative diseases.
  3. Energy Metabolism and NAD+ Synthesis:
    1. NAD+ Production: Kynurenine is involved in the synthesis of nicotinamide adenine dinucleotide (NAD+), a vital coenzyme in cellular energy metabolism. NAD+ is essential for processes such as glycolysis, the citric acid cycle, and oxidative phosphorylation.
  4. Cellular Repair and Longevity: NAD+ is also involved in DNA repair and the activation of sirtuins, proteins that regulate aging and longevity. Adequate levels of NAD+ are associated with improved mitochondrial function, reduced oxidative stress, and enhanced cellular repair mechanisms.
  5. Mental Health:
    1. Serotonin Balance: Kynurenine and its metabolites influence the availability of tryptophan for serotonin synthesis. An imbalance in the kynurenine pathway can affect serotonin levels, contributing to mood disorders such as depression and anxiety.
    2. Cognitive Function: Kynurenic acid, derived from kynurenine, has been shown to have neuroprotective effects that support cognitive function. Proper regulation of kynurenine metabolism is important for maintaining mental health and cognitive abilities, especially with aging.
  6. Oxidative Stress and Inflammation:
    1. Antioxidant Effects: Kynurenic acid has antioxidant properties that help mitigate oxidative stress, a major factor in aging and age-related diseases.
    2. Chronic Inflammation: By modulating immune responses and reducing pro-inflammatory cytokines, kynurenine helps prevent chronic inflammation, which is a hallmark of many chronic diseases and aging.
  7. Clinical and Therapeutic Implications:
    1. Biomarker for Diseases: Elevated levels of kynurenine and its metabolites are associated with various conditions, including cancer, neurodegenerative diseases, and psychiatric disorders. Measuring kynurenine levels can serve as a biomarker for diagnosing and monitoring these diseases.

The tryptophan/kynurenine (Trp/Kyn) ratio provides valuable insights into various aspects of our health, particularly related to immune function, inflammation, and overall metabolic status. This ratio reflects the balance between the availability of tryptophan and its conversion into kynurenine, mediated primarily by the enzyme indoleamine 2,3-dioxygenase (IDO), which is often activated during immune responses and inflammation.

Here’s what the Trp/Kyn ratio can tell us about our health:
  1. Immune Activation and Inflammation:
    1. Indication of Immune Response: A lower Trp/Kyn ratio typically indicates increased activity of IDO, which is upregulated in response to pro-inflammatory cytokines, such as interferon-gamma (IFN-γ). This suggests an active immune response, often seen in infections, autoimmune diseases, and chronic inflammatory conditions.
    2. Chronic Inflammation: Persistent low Trp/Kyn ratios are associated with chronic inflammatory diseases, including rheumatoid arthritis, inflammatory bowel disease, and systemic lupus erythematosus. This ratio can help monitor the extent and progression of inflammation in these conditions.
  2. Mental Health and Neurological Disorders:
    1. Depression and Anxiety: Tryptophan is a precursor to serotonin, a neurotransmitter involved in mood regulation. A lower Trp/Kyn ratio can indicate that less tryptophan is available for serotonin synthesis, potentially contributing to mood disorders such as depression and anxiety. Elevated kynurenine levels can also produce neuroactive metabolites that influence mood and cognitive function.
  3. Neurodegenerative Diseases: In conditions like Alzheimer’s disease, Parkinson’s disease, and multiple sclerosis, altered tryptophan metabolism and a reduced Trp/Kyn ratio may reflect underlying neuroinflammation and neurodegeneration.
  4. Cancer:
    1. Tumor Immune Evasion: Many tumors express high levels of IDO to evade the immune system by depleting tryptophan and producing immunosuppressive kynurenine metabolites. A lower Trp/Kyn ratio in cancer patients may indicate tumor-induced immunosuppression and can be associated with poorer prognosis.
  5. Infections:
    1. Acute and Chronic Infections: During infections, the body increases IDO activity as part of the immune response to limit pathogen growth by depleting tryptophan. A lower Trp/Kyn ratio during infection indicates active immune response and pathogen defense mechanisms.
  6. Metabolic and Systemic Health:
    1. Metabolic Disorders: Alterations in the Trp/Kyn ratio are linked to metabolic conditions such as obesity, diabetes, and cardiovascular diseases. Chronic low-grade inflammation in these conditions can lead to increased IDO activity and a lower Trp/Kyn ratio.
  7. General Health Status: The Trp/Kyn ratio can provide an overall snapshot of systemic health, reflecting the interplay between metabolism, immune function, and inflammation.

Kynurenic acid is an important metabolite in the kynurenine pathway (KP) of tryptophan metabolism. It plays several crucial roles in maintaining brain health, modulating immune responses, and protecting against neurotoxicity. Here are the key reasons why kynurenic acid is important:

  1. Neuroprotection:
    1. Glutamate Receptor Antagonism: Kynurenic acid acts as an antagonist at the N-methyl-D-aspartate (NMDA) receptor, a type of glutamate receptor. By inhibiting these receptors, kynurenic acid helps protect neurons from excitotoxicity, which is damage caused by excessive activation of glutamate receptors. Excitotoxicity is implicated in various neurodegenerative diseases, such as Alzheimer’s disease, Parkinson’s disease, and amyotrophic lateral sclerosis (ALS).
    2. Alpha-7 Nicotinic Acetylcholine Receptor (α7nAChR) Antagonism: Kynurenic acid also antagonizes α7nAChRs, which play a role in synaptic plasticity and cognitive functions. Modulation of these receptors by kynurenic acid can influence cognitive processes and neuroprotection.
  2. Anti-inflammatory Properties:
    1. Immune Modulation: Kynurenic acid has immunomodulatory effects. It modulates the activity of immune cells and reduce the production of pro-inflammatory cytokines. By dampening excessive immune responses, kynurenic acid helps prevent chronic inflammation, which is associated with various diseases, including autoimmune disorders and neuroinflammation.
  3. Antioxidant Effects:
    1. Scavenging Free Radicals: Kynurenic acid has antioxidant properties, allowing it to neutralize reactive oxygen species (ROS) and reduce oxidative stress. Oxidative stress is a key factor in aging and the development of neurodegenerative diseases. By reducing oxidative damage, kynurenic acid supports cellular health and longevity.
  4. Role in Cognitive Function:
    1. Modulation of Neurotransmission: Kynurenic acid influences neurotransmitter systems, including glutamate and acetylcholine pathways, which are critical for cognitive functions such as learning and memory. By modulating these pathways, kynurenic acid affect cognitive performance and protect against cognitive decline.
  5. Role in Aging:
    1. Anti-aging Effects: By protecting neurons from excitotoxicity, reducing oxidative stress, and modulating immune responses, kynurenic acid contributes to the maintenance of brain health and overall longevity. Balancing kynurenine pathway metabolites to favor neuroprotective kynurenic acid over neurotoxic quinolinic acid is a potential strategy to support healthy aging.
  6. Metabolic Health:
    1. Glucose and Lipid Metabolism: Emerging research indicates that kynurenic acid may have a role in regulating glucose and lipid metabolism, thus potentially impacting metabolic health and the management of conditions such as diabetes and obesity.
  7. Conclusion: Kynurenic acid is a vital metabolite with multiple protective roles in the body. Its neuroprotective, anti-inflammatory, and antioxidant properties make it crucial for maintaining brain health, modulating immune responses, and protecting against various forms of cellular damage. Understanding the balance of kynurenine pathway metabolites and how to modulate them offers significant potential for therapeutic interventions in neurodegenerative diseases, psychiatric disorders, and overall health and longevity.

Quinolinic acid (QA) is a metabolite in the kynurenine pathway (KP) of tryptophan metabolism. While it plays a necessary role in certain physiological processes, it is also associated with neurotoxicity and various pathological conditions.

Here are the key aspects of the importance and implications of quinolinic acid:

  1. Role in NAD+ Synthesis:
    1. Precursor for NAD+: Quinolinic acid is a precursor in the biosynthesis of nicotinamide adenine dinucleotide (NAD+), a critical coenzyme involved in cellular energy production, DNA repair, and regulation of cellular metabolism. NAD+ is essential for mitochondrial function and overall cellular health.
  2. Neurotoxicity:
    1. Excitotoxicity: Quinolinic acid acts as an agonist at NMDA receptors, a type of glutamate receptor. Excessive activation of NMDA receptors by quinolinic acid leads to excitotoxicity, which results in neuronal damage and cell death. This excitotoxic effect is implicated in various neurodegenerative diseases such as Alzheimer’s disease, Parkinson’s disease, Huntington’s disease, and amyotrophic lateral sclerosis (ALS).
    2. Oxidative Stress: Quinolinic acid can induce the production of reactive oxygen species (ROS), contributing to oxidative stress and further neuronal damage. Oxidative stress is a significant factor in the progression of neurodegenerative diseases.
  3. Inflammation:
    1. Pro-inflammatory Effects: Quinolinic acid is produced by activated microglia and macrophages during immune responses and inflammation. Elevated levels of quinolinic acid are often associated with chronic inflammatory conditions, including neuroinflammatory diseases, multiple sclerosis, and infections such as HIV.
  4. Cognitive and Psychiatric Implications:
    1. Cognitive Dysfunction: High levels of quinolinic acid in the brain are linked to cognitive impairments and memory deficits. This is due to its neurotoxic effects and disruption of normal neurotransmission.
    2. Psychiatric Disorders: Altered levels of quinolinic acid have been implicated in psychiatric conditions such as depression, schizophrenia, and bipolar disorder. Inflammatory processes that increase quinolinic acid production can contribute to the pathophysiology of these disorders.
    3. HIV-associated Neurocognitive Disorders:
      HIV Infection: Quinolinic acid levels are significantly elevated in the brains of individuals with HIV infection, contributing to HIV-associated neurocognitive disorders (HAND). The neurotoxic effects of quinolinic acid play a role in the cognitive decline seen in HIV patients.
  5. Immune System Modulation:
    1. Immune Response: Quinolinic acid is involved in modulating the immune response. During infections and immune activation, its production can help regulate immune functions but also contributes to neurotoxicity when levels become excessively high.

Our body acquires NAD+ through de novo synthesis from tryptophan, the Preiss-Handler pathway from dietary niacin, and the salvage pathway recycling nicotinamide. Additionally, dietary sources of niacin and supplements like nicotinamide riboside (NR) and nicotinamide mononucleotide (NMN) can boost NAD+ levels. The balance of NAD+ and NADH is crucial for energy production, redox balance, DNA repair, cellular signaling, and overall health.

  1. De Novo Synthesis Pathway: The de novo synthesis pathway of NAD+ starts with the amino acid tryptophan and proceeds through the kynurenine pathway. This pathway involves several steps:
    1. Tryptophan Conversion: Tryptophan is converted to N-formylkynurenine by the enzyme indoleamine 2,3-dioxygenase (IDO) or tryptophan 2,3-dioxygenase (TDO).
    2. Kynurenine Formation: N-formylkynurenine is then converted to kynurenine.
    3. Quinolinic Acid Production: Kynurenine is further metabolized to 3-hydroxykynurenine and then to 3-hydroxyanthranilic acid, leading to the production of quinolinic acid.
    4. NAD+ Synthesis: Quinolinic acid is converted to nicotinic acid mononucleotide (NAMN) by the enzyme quinolinate phosphoribosyltransferase (QPRT). NAMN is then converted through a series of enzymatic steps to NAD+.
  2. Preiss-Handler Pathway: The Preiss-Handler pathway synthesizes NAD+ from dietary niacin (vitamin B3) in the form of nicotinic acid:
    1. Nicotinic Acid to Nicotinic Acid Mononucleotide (NAMN): Nicotinic acid is converted to NAMN by the enzyme nicotinic acid phosphoribosyltransferase (NAPRT).
    2. NAMN to Nicotinic Acid Adenine Dinucleotide (NAAD): NAMN is then converted to NAAD.
    3. NAAD to NAD+: Finally, NAAD is amidated to NAD+ by the enzyme NAD+ synthetase (NADS).
  3. Salvage Pathway: The salvage pathway recycles nicotinamide, a form of vitamin B3, to synthesize NAD+:
    1. Nicotinamide to Nicotinamide Mononucleotide (NMN): Nicotinamide is converted to NMN by the enzyme nicotinamide phosphoribosyltransferase (NAMPT).
    2. NMN to NAD+: NMN is then converted to NAD+ by the enzyme nicotinamide mononucleotide adenylyltransferase (NMNAT).
  4. Dietary Sources and Supplements: NAD+ can also be influenced by dietary intake and supplements:
    1. Dietary Niacin: Foods rich in niacin, such as meat, fish, poultry, grains, and certain vegetables, provide nicotinic acid and nicotinamide, which can be converted to NAD+.
    2. NAD+ Precursors: Supplements such as nicotinamide riboside (NR) and nicotinamide mononucleotide (NMN) are direct precursors to NAD+ and can increase NAD+ levels in the body. These precursors are efficiently converted to NAD+ through the salvage pathway.
  5. Importance of NAD+/NADH Balance:
    1. Energy Production: NAD+ and NADH are crucial for cellular respiration. NAD+ acts as an electron acceptor in glycolysis and the citric acid cycle, becoming reduced to NADH. NADH then donates electrons to the electron transport chain, driving ATP production.
    2. Redox Reactions: The balance between NAD+ and NADH is essential for maintaining cellular redox status. NAD+/NADH ratio influences many metabolic processes and cellular functions.
    3. DNA Repair and Sirtuins: NAD+ is a substrate for enzymes involved in DNA repair (PARPs) and for sirtuins, which regulate aging and longevity by deacetylating proteins and influencing gene expression.
    4. Immune Function: NAD+ plays a role in regulating immune responses and inflammation.

5-Hydroxytryptophan (5-HTP) is a naturally occurring amino acid and chemical precursor in the biosynthesis of serotonin, a crucial neurotransmitter that plays significant roles in regulating mood, sleep, appetite, and various other physiological functions.

The importance of 5-HTP lies in its role in serotonin production and its potential therapeutic benefits. Here’s why 5-HTP is important:
  1. Serotonin Synthesis:
    1. Direct Precursor: 5-HTP is the immediate precursor to serotonin (5-hydroxytryptamine or 5-HT). It is synthesized from the essential amino acid tryptophan through the action of the enzyme tryptophan hydroxylase. 5-HTP is then converted to serotonin by the enzyme aromatic L-amino acid decarboxylase (AADC).
    2. Bypassing Rate-Limiting Step: Since 5-HTP is downstream of the rate-limiting step (tryptophan to 5-HTP) in serotonin synthesis, supplementing with 5-HTP can effectively increase serotonin levels, potentially bypassing limitations in tryptophan hydroxylase activity.
  2. Mood Regulation:
    1. Antidepressant Effects: Serotonin is known for its mood-stabilizing effects. Low levels of serotonin are associated with depression and anxiety. By increasing serotonin levels, 5-HTP supplementation may help alleviate symptoms of depression and anxiety. Several studies have suggested that 5-HTP may be as effective as some antidepressant medications for improving mood.
    2. Anxiety Reduction: Higher serotonin levels can help reduce anxiety by promoting relaxation and improving emotional regulation.
  3. Sleep Improvement:
    1. Melatonin Production: Serotonin is a precursor to melatonin, the hormone that regulates the sleep-wake cycle. By boosting serotonin levels, 5-HTP can increase melatonin production, thereby improving sleep quality and helping with sleep disorders such as insomnia.
    2. Enhanced Sleep Patterns: Improved serotonin and melatonin levels contribute to better sleep patterns, which are essential for overall health and well-being.
  4. Appetite Control and Weight Management:
    1. Satiety and Appetite Regulation: Serotonin influences appetite and satiety. Higher serotonin levels can reduce food cravings and increase feelings of fullness, potentially aiding in weight management. 5-HTP supplementation has been shown to reduce food intake and promote weight loss in some studies.
    2. Reduction in Emotional Eating: By stabilizing mood and reducing anxiety, 5-HTP can help reduce emotional eating and cravings for carbohydrates, which are often associated with low serotonin levels.
  5. Pain Management:
    1. Fibromyalgia and Chronic Pain: Some studies have indicated that 5-HTP supplementation can help reduce pain and improve symptoms in conditions such as fibromyalgia. This is likely due to its role in increasing serotonin levels, which modulate pain perception.
  6. Migraine Prevention:
    1. Serotonin and Migraines: Low serotonin levels have been linked to the occurrence of migraines. 5-HTP supplementation may help prevent migraines by increasing serotonin levels and improving vascular tone.
  7. Improvement in Neurological Disorders:
    1. Parkinson’s Disease: In some cases, 5-HTP is used as an adjunct therapy for Parkinson’s disease to manage symptoms related to serotonin deficiency.
  8. Safety and Considerations:
    1. Potential Side Effects: While 5-HTP is generally well-tolerated, some individuals may experience side effects such as gastrointestinal issues, headache, or dizziness. It’s important to start with a low dose and gradually increase it under medical supervision.
    2. Interactions with Medications: 5-HTP should be used cautiously in combination with other serotonergic medications (e.g., SSRIs, MAOIs) due to the risk of serotonin syndrome, a potentially life-threatening condition caused by excessive serotonin levels.
    3. Supplement Quality: Ensuring the quality and purity of 5-HTP supplements is crucial, as contaminants can cause adverse effects.

Serotonin, also known as 5-hydroxytryptamine (5-HT), is a crucial neurotransmitter that plays a significant role in various physiological and psychological processes.

Its importance extends across multiple aspects of health and well-being, influencing mood, behavior, and bodily functions. Here are some key reasons why serotonin is important:
  1. Mood Regulation:
    1. Antidepressant Effects: Serotonin is often referred to as the “feel-good” neurotransmitter due to its significant role in mood stabilization and happiness. Low levels of serotonin are associated with mood disorders such as depression and anxiety. Many antidepressant medications, such as selective serotonin reuptake inhibitors (SSRIs), work by increasing serotonin levels in the brain.
    2. Anxiety Reduction: Adequate serotonin levels help regulate anxiety, reducing feelings of stress and promoting emotional stability.
  2. Sleep Regulation:
    1. Sleep-Wake Cycle: Serotonin is a precursor to melatonin, the hormone that regulates the sleep-wake cycle. Serotonin levels influence sleep patterns, and disruptions in serotonin lead to sleep disorders such as insomnia.
    2. Sleep Quality: Proper serotonin levels contribute to improved sleep quality, which is essential for overall health, cognitive function, and emotional well-being.
  3. Appetite and Digestion:
    1. Appetite Control: Serotonin plays a role in regulating appetite and satiety. It helps control food intake by promoting feelings of fullness and reducing food cravings, particularly for carbohydrates.
    2. Gut Function: The majority of the body’s serotonin is found in the gastrointestinal tract, where it regulates bowel movements and function. Serotonin is involved in the coordination of smooth muscle contractions, aiding in digestion and gut motility.
  4. Cognitive Functions:
    1. Memory and Learning: Serotonin impacts various cognitive functions, including memory, learning, and decision-making. Adequate serotonin levels support cognitive processes and overall brain health.
    2. Attention and Focus: Serotonin helps regulate attention and focus, contributing to better cognitive performance and mental clarity.
  5. Pain Modulation:
    1. Pain Perception: Serotonin modulates pain perception and is involved in the body’s response to pain. Low serotonin levels can increase pain sensitivity, while adequate levels help reduce the perception of pain.
    2. Chronic Pain Management: Conditions such as fibromyalgia and migraines are associated with serotonin dysfunction. Increasing serotonin levels can help manage chronic pain and improve symptoms.
  6. Cardiovascular Health:
    1. Vascular Tone: Serotonin influences the contraction and relaxation of blood vessels, playing a role in maintaining vascular tone and blood pressure. It helps regulate cardiovascular function and supports overall heart health.
    2. Platelet Function: Serotonin is stored in platelets and released during clot formation, playing a role in hemostasis and wound healing.
  7. Hormonal Balance:
    1. Reproductive Health: Serotonin interacts with various hormones and neurotransmitters, influencing reproductive health and menstrual cycle regulation. It affects hormonal balance and reproductive behaviors.
  8. Mental Health:
    1. Stress Response: Serotonin is involved in the body’s response to stress and helps regulate emotional reactions to stressful situations.
    2. Psychiatric Disorders: Dysregulation of serotonin is linked to several psychiatric disorders, including obsessive-compulsive disorder (OCD), schizophrenia, and bipolar disorder. Therapeutic strategies often aim to normalize serotonin levels to manage these conditions.

Melatonin is a hormone primarily produced by the pineal gland in the brain. It plays a crucial role in regulating sleep-wake cycles and maintaining circadian rhythms. Beyond its well-known role in sleep regulation, melatonin has various other physiological and potential therapeutic effects.

Here’s why melatonin is important:
  1. Regulation of Sleep-Wake Cycles:
    1. Circadian Rhythm: Melatonin is often referred to as the “sleep hormone” because it helps regulate the body’s internal clock, or circadian rhythm. Its production increases in the evening, promoting sleep, and decreases in the morning, promoting wakefulness.
    2. Sleep Quality: Adequate melatonin levels are essential for initiating and maintaining sleep. Supplementation with melatonin can help improve sleep quality, particularly in individuals with sleep disorders such as insomnia, jet lag, or shift work sleep disorder.
  2. Antioxidant Properties:
    1. Free Radical Scavenger: Melatonin has potent antioxidant properties. It neutralizes free radicals and reduces oxidative stress, protecting cells from damage. This is particularly important in protecting the brain, which is highly susceptible to oxidative damage.
    2. DNA Repair: Melatonin helps in the repair of damaged DNA and supports overall cellular health.
  3. Immune System Support:
    1. Immunomodulation: Melatonin modulates immune function and enhances the body’s defense mechanisms. It has been shown to have anti-inflammatory properties, which can help regulate immune responses and reduce chronic inflammation.
    2. Infection and Cancer: There is evidence to suggest that melatonin can improve outcomes in infections and may have potential anti-cancer properties due to its role in modulating immune responses and reducing oxidative stress.
  4. Neuroprotective Effects:
    1. Brain Health: Melatonin protects neurons from oxidative stress and has been shown to have neuroprotective effects. It is being studied for its potential role in preventing or slowing the progression of neurodegenerative diseases such as Alzheimer’s and Parkinson’s disease.
    2. Cognitive Function: By improving sleep quality and reducing oxidative stress, melatonin supports cognitive function and overall brain health.
  5. Mood Regulation:
    1. Seasonal Affective Disorder (SAD): Melatonin levels influence mood, and disturbances in melatonin production are associated with mood disorders such as seasonal affective disorder (SAD). Melatonin supplementation help regulate mood and alleviate symptoms of SAD.
    2. Depression and Anxiety: Some research suggests that melatonin may have a role in alleviating symptoms of depression and anxiety, likely due to its impact on sleep and circadian rhythms.
  6. Reproductive Health:
    1. Fertility and Menstrual Cycle: Melatonin influences reproductive hormones and plays a role in regulating menstrual cycles and fertility. It has antioxidant effects that support reproductive health.
    2. Pregnancy: Adequate melatonin levels are important during pregnancy for maintaining a healthy circadian rhythm, which affect both maternal and fetal health.
  7. Metabolic Health:
    1. Glucose Metabolism: Melatonin is involved in regulating glucose metabolism and insulin sensitivity. Disruptions in melatonin production impact metabolic health and are associated with an increased risk of conditions such as diabetes and obesity.
    2. Weight Management: Proper sleep regulation through melatonin influences appetite control and weight management.
  8. Cardiovascular Health:
    1. Blood Pressure Regulation: Melatonin helps regulate blood pressure by influencing the tone and function of blood vessels. It has been shown to have cardioprotective effects, including reducing the risk of hypertension and other cardiovascular diseases.
  • SST tube of blood, serum
  • saliva

7 – 10 days

Price: $235.00