Pyrroloquinoline

Pyrroloquinoline quinone (PQQ) is a peptide-derived redox cofactor, significant in mitochondriogenesis, reproduction, growth, and aging. 

PQQ enhances mitochondrial function by boosting NAD+-dependent sirtuin activity and the expression of key targets like PGC-1α, NRF-1, and TFAM, contributing to its antioxidant properties. 

It is known to mitigate conditions such as ischemia, inflammation, and lipotoxicity, and it exhibits nootropic properties. 

Often referred to as a "longevity vitamin," PQQ is considered a therapeutic nutraceutical with vitamin-like properties. Originally identified as a cofactor for bacterial dehydrogenases, PQQ is now recognized as the third most common redox coenzyme, following nicotinamide and flavin nucleotides. 

Present in certain bacteria, foods, and human tissues, especially breast milk, PQQ cannot be synthesized by the human body but offers extensive health benefits, including antioxidant protection, immune modulation, energy metabolism, neuroprotection, and inflammation reduction.

What is Pyrroloquinoline?

Pyrroloquinoline, also known as pyrroloquinoline quinone (PQQ), is an peptide-derived redox factor. 

PQQ is important in mitochondriogenesis, reproduction, growth, and aging.  It promotes mitochondrial function and exerts antioxidant capacity by enhancing NAD+-dependent sirtuin activity and the expression of targets such as PGC-1α, NRF-1, and TFAM. [6.] 

PQQ mitigates conditions like ischemia, inflammation, and lipotoxicity and exhibits nootropic properties. [6.]

PQQ is considered a therapeutic nutraceutical with vitamin-like properties, and called by some a “longevity vitamin” due to its beneficial support for mitochondria-related cellular functions. [10., 14.] It is also considered by some to be “the new B vitamin.” [12.] 

PQQ was identified as a cofactor for bacterial dehydrogenases in the late 1960s; it was later recognized as essential for various biological functions. 

Now, after nicotinamide nucleotides and flavin nucleotides, PQQ is considered the third most common redox coenzyme. [12.] 

Production and Sources of Pyrroloquinoline 

PQQ is primarily produced by certain bacteria, and it is also present in some foods and in breast milk. [4.] It cannot be synthesized by the human body. 

What are the Benefits of Pyrroloquinoline Quinone (PQQ)? [10.] 

Antioxidant Properties

PQQ is a potent orthocyclic antioxidant that scavenges free radicals, providing protection against oxidative stress. It acts as an anti-neurological, anti-degenerative, anti-melanogenic, and anti-cancer agent.

Immune Modulation

PQQ influences the immune system by modulating CD4 cell counts and IL-2 production. It enhances immunity by increasing IgA levels and regulating T-cell proliferation.

Energy Metabolism

PQQ is crucial for mitochondrial biogenesis and ATP production. It supports cellular energy production by participating in glucose and carbohydrate metabolism and reducing reactive oxygen species (ROS).

Growth and Repair

PQQ stimulates growth in bacteria and plants by promoting cell reproduction and enhancing phosphate solubilization. In humans, it supports connective tissue growth and repair, improving skin health and elasticity.

Neuroprotection

PQQ enhances nerve growth factor (NGF) production, protects against neurological injuries, and improves cognitive functions. It has shown potential in treating conditions like Alzheimer's, Parkinson's, and traumatic brain injuries.

Inflammation and Disease

PQQ reduces inflammation by modulating various signaling pathways such as STAT, MAPK, JAK, and PI3K/Akt. It decreases the production of pro-inflammatory cytokines and oxidative stress markers.

Cell Signaling and Regulation

PQQ influences numerous cellular signaling pathways, including ERK1/2, mTOR, and cAMP, contributing to cell proliferation, differentiation, apoptosis, and metabolic regulation.

Sleep and Relaxation

PQQ improves sleep quality by regulating the PGC-1 alpha pathway, reducing fatigue, and enhancing overall sleep maintenance.

Food Sources of PQQ [7.]

• Broad Bean: 17.8 ng/g
• Green Soybeans: 9.26 ng/g
• Potato: 16.6 ng/g
• Sweet Potato: 13.3 ng/g
• Parsley: 34.2 ng/g
• Cabbage: 16.3 ng/g
• Carrot: 16.8 ng/g
• Celery: 6.33 ng/g
• Green Pepper: 28.2 ng/g
• Spinach: 21.9 ng/g
• Tomato: 9.24 ng/g
• Apple: 6.09 ng/g
• Banana: 12.6 ng/g
• Kiwi Fruit: 27.4 ng/g
• Orange: 6.83 ng/g
• Papaya: 26.7 ng/g
• Green Tea: 29.6 ng/ml
• Oolong Tea: 27.7 ng/ml
• Coke: 20.1 ng/ml
• Whiskey: 7.93 ng/ml
• Wine: 5.79 ng/ml
• Sake (Rice Wine): 3.65 ng/ml
• Bread: 9.14 ng/g
• Fermented Soybeans (Natto): 61.0 ng/g
• Miso (Bean Paste): 16.7 ng/g
• Tofu (Bean Curd): 24.4 ng/g

Pyrroloquinoline Quinone (PQQ) in Health and Disease

PQQ, the “longevity vitamin,” promotes optimal cellular health. Low levels of PQQ have been associated with:

Impaired Immune Function

Low PQQ levels can lead to defects in immune responses, resulting in reduced white blood cell function and increased susceptibility to infections. PQQ functions are known to enhance the immune response. [6.] 

Mitochondrial Dysfunction

Insufficient PQQ may contribute to poor mitochondrial health, which is implicated in various conditions such as mental decline, heart disease, diabetes, and cancer. [6.] 

Cognitive Decline 

Higher PQQ levels are associated with improvements in cognitive function. PQQ's benefits are linked to its role in mitochondrial biogenesis and antioxidant activity. .[14.] 

Cardiovascular Diseases

A deficiency in PQQ may exacerbate conditions like heart disease, as it is crucial for maintaining heart health and myocardial mitochondrial function, and reducing oxidative stress in cardiac tissues. [15.] 

It may also prevent cardiac fibrosis and improve cardiac function. [13.] 

Diabetes and Metabolic Syndrome

Low levels of PQQ are linked to increased inflammation and oxidative stress, which are key factors in the development of diabetes and related metabolic disorders. [5.] 

PQQ appears to have a greater protective benefit against the damaging effects of diabetes and hyperglycemia, rather than a direct glucose-lowering effect. [1.] 

Obesity 

Pyrroloquinoline quinone (PQQ) has shown potential health benefits, particularly in preventing obesity and preserving muscle mass in obese animal models. [11.] 

Increased Inflammation

PQQ has anti-inflammatory properties; thus, low levels may lead to higher inflammatory markers and greater risks of inflammatory diseases. [12.] 

Fatigue and Stress

Insufficient PQQ may result in decreased energy production at the cellular level, leading to chronic fatigue and reduced overall vitality.

One small study of 17 participants showed that 8 weeks of daily supplementation of 20 mg PQQ reduced fatigue and perceived stress, and increased beneficial sleep and quality of life. [9.] 

Early Skin Aging

One small study showed that female participants taking 20 mg oral PQQ reported a subjective improvement in skin conditions, particularly dry skin and elasticity. [8.] 

Laboratory Testing for PQQ

Currently, testing for levels of PQQ in humans is not widely available. However, tests to assess mitochondrial function are readily available through various companies. Testing for mitochondrial function is commonly done by assessing organic acids. 

What Are Organic Acids?  [2., 3.]

Organic acids are organic compounds with acidic properties.  They include a variety of functional groups like carboxyl, phenol, enol, and thiol, with carboxylic acids having the strongest acidity.

Organic acids are considered weak acids, with those containing phenol, enol, alcohol, or thiol groups being even weaker.  

Their structures vary in terms of carbon chain types—aromatic, aliphatic, alicyclic, heterocyclic—saturation, substitutions, and the number of functional groups. 

These acids play critical roles in metabolic and catabolic pathways, notably in the tricarboxylic acid cycle inside mitochondria, which is central to energy production in eukaryotes.  They are also pivotal in determining the sensory properties of fruits and vegetables.

Organic Acid Testing in Functional Medicine

In functional medicine, organic acid testing is utilized to evaluate a patient's metabolic function through a simple urine test. This testing can identify metabolic imbalances that may affect a patient’s mood, energy, and overall health. 

Testing provides insights into nutrient deficiencies, dietary habits, toxic exposures, and gut microbiome activity. 

The results assist practitioners in customizing treatment plans to address specific metabolic dysfunctions and improve health outcomes. 

Additionally, it helps in assessing the impact of microbial metabolism and the efficiency of the Krebs Cycle, aiding in personalized healthcare.

Organic Acid Test Information, Sampling Methods and Preparation

Laboratory testing for organic acids is typically done in urine, although it can also be tested in blood.  Testing may be ordered to diagnose an inborn metabolic disorder, or to assess metabolic function and gastrointestinal health in a functional medicine setting.  

Urine samples may be collected in a clinical setting; they can also be collected at home.  Some labs recommend or require a first morning void sample, to provide a concentrated sample.  

Interpreting Organic Acid Test Results

Interpretation of organic acid test results requires a comprehensive assessment of various organic acids, and possibly other vitamins, minerals, and biomarkers, for a full picture of mitochondrial health and function. 

Reputable resources are available to learn more about mitochondrial health assessment, including the following:

Class: How to Use Metabolomics Testing to Identify and Correct Mitochondrial Dysfunction

Article: Mitochondria - What They Are, Why We Should Care, and How to Support Them Using Functional Medicine Strategies

Order Testing for Mitochondrial Health

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