On February 2, 2023, the National Health Commission issued the acceptance announcement of Pyrroloquinoline Quinone Disodium Salt (PQQ), Acceptance No.: Wei Food Xin Shen Zi (2023) No. 0001, which is the first new food ingredient accepted in 2023, after PQQ had been approved as a new food ingredient in March 2022 in the Announcement of the National Health Commission No. 1 of 2022, and its production process is Chemical synthesis method, which can be applied in beverage field.

Process (synthetic method): Pyrroloquinone Disodium Salt is made from ethyl 6-amino-5-methoxy-1H-ming-2-antelate and dimethyl 2-oxopentenedioate as raw materials, through the processes of coupling ring-forming reaction, whatshoing ring formation, oxidation reaction, cool hydrolysis reaction, and refining.

Specification and application: The purity of the product is ≥98.0 g/100 g (on dry basis). Recommended serving size is ≤20 mg/day (i.e. the recommended serving size of this product is ≤20 mg/day if the content of pyrroloquinoline quinone disodium salt is 98.0g/100g, and the serving size of the product exceeding this content is converted according to the actual content).

Scope of use and maximum use: Beverage (40 mg/kg, solid beverages are converted according to the liquid mass after brewing).

As a matter of fact, process-wise, many domestic enterprises adopt microbial fermentation and synthesis method to produce PQQ, and the fermentation method process of PQQ has a long history and has also been recognized abroad. However, our country currently stipulates that the scope of use of fermentation-derived PQQ is only for export as well as in the domestic animal feed sector. Domestic manufacturers, such as Zhucheng Haotian Pharmaceuticals Fujian Yubaifu Biotechnology Co., Ltd, Fuzhou Kangtai Biotechnology Co., Ltd, Shandong Jincheng Pharmaceuticals, Zhejiang Pharmaceuticals, etc., use the fermentation process to produce PQQ, and the sales of their products have long been dominated by exports. Therefore, if the fermentation process of PQQ is approved, it will greatly reduce the cost and rapidly promote the development of PQQ towards market application.

What is PQQ

Pyrroloquinolinequinone disodium salt (PQQ), abbreviated as PQQ, chemical formula C14H6N2O8, is a new cofactor with similar physiological functions as vitamins, which is widely found in prokaryotes, plants and mammals, but at very low levels, e.g., fermented soybeans or natto, milk, eggs, spinach, peppers, kiwi, parsley, tea, papaya, spinach, celery, and breast milk. Among them, natto has the highest content of PQQ among common foods, which is about 61ng/g; and breast milk, which has the highest content of PQQ found so far, only contains 140-180ng/ml. Animal studies have shown that a lack of PQQ hinders growth, impairs immunity, and leads to reproduction and metabolic problems, etc. Therefore, PQQ exists in plants and animals and participates in their growth and development, and is an indispensable nutrient for human growth. It is an indispensable nutrient for human growth.

In 1979, American scientists discovered PQQ by using X-ray crystal diffraction technology, and PQQ has become the third coenzyme of oxidoreductase discovered after nicotinamide nucleotide (NAD+ and NADP+) and flavin nucleotide (FAD and FMN).The biological function of PQQ mainly focuses on two aspects, which is able to support mitochondrial growth and development, and stimulate the rapid growth of human cells; PQQ has excellent antioxidant properties, which can help remove free radicals and reduce cell damage; these two functions make it powerful in brain health, cardiovascular health, metabolic health, etc., mainly to help physical recovery, anti-fatigue, etc. Therefore, the world medical profession called “PQQ”, which is the third coenzyme of oxidoreductase after the discovery of PQQ.

Therefore, it is called “the 14th vitamin” and “the king of immunity” by the world medical profession, and is known as “super vitamin” in the United States, which is the most powerful biological active substance discovered by human beings so far. It is the most potent biological active substance discovered by mankind so far, which can stimulate the growth of human cells, and a trace amount of PQQ can improve the metabolism and growth function of the organism’s tissues. The main performance is:

✦ Improved mitochondria
PQQ helps to optimize energy production, with powerful mitochondrial energy replenishment and mitochondrial autophagy; it also stimulates mitochondrial biosynthesis, leading to an increase in the amount synthesized and enhanced function, which in turn improves mitochondrial utilization.In 2013, researchers at the University of California Nutrition Center administered PQQ supplements to 10 people (5 men and 5 women) and tested the effects after 76 hours The experimental group taking PQQ had about 163% more fresh mitochondria in their cells, as measured by blood and urine tests.

The King of Immunity
PQQ is the most potent biologically active substance ever discovered. It stimulates the growth of the body’s B cells, T cells and other lymphocytes, causing them to produce antibodies, thus improving the body’s immune function in general.

✦Strong oxidizing agent
PQQ is a very potent antioxidant and has the unique benefit of generating a greater degree of near-continuous catalytic cycling, which is the ability to carry out repeated oxidation and reduction reactions.PQQ is capable of 20,000 catalytic conversions, whereas vitamin C provides only four catalytic conversions, meaning that PQQ provides 5,000 times the functional antioxidant protection of vitamin C. PQQ is also a powerful antioxidant, and has been shown to be a powerful antioxidant for many years, including in the United States.

✦ Helps Brain Cognition and Memory
PQQ ameliorates neuronal damage due to the oxygen-glucose deprivation model, reduces alterations in the content of Nysted’s vesicles caused by factor D-galactose treatment, inhibits neuronal degeneration, has a debilitating effect on β-amyloid-induced nerve damage, and helps to promote the secretion of neurotrophic factors; PQQ also inhibits the formation of peroxynitrite, potentially oxidizing the N-methyl-D-aspartate (NMDA) receptor redox sites, thereby reducing NMDA receptor activity; also, can act as a potent antioxidant to protect mitochondrial lipids and proteins, and has been shown to protect mitochondrial function from oxidative damage and promote new mitochondria and neuron generation; in addition, PQQ has significant memory retention and dementia prevention effects.

✦Detoxification
Japanese scientists found that PQQ can speed up the rate of oxidation of acetaldehyde into acetic acid to reduce the level of acetaldehyde in the body, thus it is expected to reduce the toxic damage caused by alcohol consumption to the liver. Chinese scholars found that oral consumption of PQQ can effectively reduce blood lead, brain lead, liver lead levels, and does not cause the loss of beneficial metal elements zinc and copper in the body.

Anti-inflammatory
PQQ has antioxidant properties that can help neutralize harmful free radicals and prevent cell damage and inflammation. Studies have shown that after just three days, supplementation with PQQ significantly reduces many markers of inflammation.

✦ Improved Reproductive Function
PQQ may improve reproductive function in animals, inhibit ovarian aging with age, and regulate the environment for follicular maturation and ovulation, a deficiency of which may lead to abnormal fertility.

✦Benefits cardiovascular health
PQQ can inhibit the production of ROS in cardiomyocytes and the decrease of mitochondrial membrane potential, thus reducing the death of cardiomyocytes. This protects the heart and prevents myocardial ischemia and myocardial infarction.

✦Hepatoprotective effect
PQQ can protect the liver against alcohol- and carbon tetrachloride-induced liver damage and TAA-induced liver fibrosis.

✦Activate longevity gene
The authoritative journals “journal of cell science” and “PNAS” published that PQQ can activate two major longevity-related genes, SIRT1 and SIRT3.

Certification of PQQ in foreign markets

In recent years, with the growing awareness, PQQ has realized the most comprehensive efficacy certification, and the U.S. and the European Union have classified it as a high safety dietary supplement.

USA: PQQ has obtained GRAS certification from the U.S. Food and Drug Administration (FDA), and can be used as an ingredient in energy drinks, sports drinks, electrolyte drinks, and bottled water and other food products; the first PQQ dietary supplement was first approved in the U.S. in 2009, and the supplement ingredient is the sodium salt of PQQ (PQQ-2Na+), due to the fact that PQQ is slightly soluble in water.

EU: On August 13, 2018, the European Commission (ESFA) issued Regulation (EU) 2018/1122 approving pyrroloquinoline quinone sodium salt as a novel food. In accordance with Regulation (EU) 2015/2283 of the European Parliament and of the Council, the European Commission amended the Annex to the Implementing Regulation (EU) 2017/2470 for the use of pyrroloquinoline quinone sodium salt as a dietary supplement as defined in Directive 2002/46/EC for the target population of adults, excluding pregnant and lactating women, with a maximum dosage of pyrroloquinoline quinone sodium salt of 20mg/day.

Canada: In 2012, Health Canada (HC) approved PQQ as a natural health food.

Japan: In 2013, Japan’s Ministry of Health, Labor and Welfare (MHLW) recognized PQQ as classified as a non-pharmaceutical in the Food and Drug Classification.

Applications of PQQ

The common PQQ supplements on the market today are mainly for brain health, sleep aid, energy supplementation, oral beauty, pregnancy aid, etc. They are often used in conjunction with various ingredients such as Coenzyme Q10, GABA (Γ-aminobutyric acid), Ginkgo biloba leaf extract, phosphatidylserine (PS), and so on.

PQQ + Coenzyme Q10 for heart health
PQQ and Coenzyme Q10 are both involved in mitochondrial energy production, and their synergistic use yields better results. This combination is one of the most common combinations in PQQ-related supplements today, and is mainly used in heart-healthy, energy-boosting, and brain-boosting types of supplements.

PQQ + PS for Brain Health
Over time, the mitochondria of the nervous system and nerve cells in the brain deteriorate. In addition to impairing memory and concentration, mitochondrial degeneration has been linked to diseases such as Alzheimer’s and Parkinson’s. PQQ is supplemented with beneficial ingredients such as PS, which not only stops mitochondrial degradation, but also supports better brain performance and enhanced memory.

PQQ+GABA for Sleep Health
PQQ is able to alleviate sleep disorders caused by anxiety by lowering the stress hormone cortisol, effectively reducing the time it takes to fall asleep and improving the quality of sleep, and can be used in conjunction with sleep-aid ingredients such as GABA.

Others
PQQ can also be used with Pueraria Mirifica, Turmeric, Probiotics, etc. for detoxification, and with Vitamin C, Zinc, Vitamin D, etc. for boosting the body’s immunity.

In recent years, with the deepening of knowledge, PQQ has realized the most comprehensive efficacy certification, and is widely used as dietary supplements or food in many countries and regions around the world. In terms of the current market distribution of PQQ applications, it is still more concentrated in overseas markets, and is often used in energy drinks, sports drinks, electrolyte drinks, nutritional supplements and so on. Few products have been marketed domestically, mostly in the form of solid beverages, and the end products are usually made into small-dose beverages by adding other functional ingredients in addition to the main ingredients of PQQ.

As a new ingredient, PQQ has been recognized for its positive effects on nutrition and health. Due to its powerful function, high safety and good stability, it has a broad development prospect in the field of functional food.