PQQ Reduces Arthritis InflammationJanuary 2017
By Chancellor Faloon
Pyrroloquinoline quinone, or PQQ, is a vitamin-like compound that has demonstrated impressive biological effects. It is found in tiny quantities in plant foods.1
PQQ is responsible for creating new mitochondria as well as maintaining existing mitochondria within the cell.2 PQQ’s unique abilities have led many researchers to believe it can slow down the progression of aging.
Past studies have shown that PQQ can improve cardiovascular and brain health.3-8 More recent research has shown that PQQ can inhibit breakdown of healthy bone.
The latest findings indicate that PQQ has the potential to decelerate the deterioration of joints in rheumatoid arthritis and osteoarthritis.10,11
Arthritis is a leading cause of disability in the US.12 An urgent need exists to find treatments to prevent or delay its onset. Recent studies published in the journal Inflammation indicate PQQ may very well exert a protective effect in the joints.10,11
Rheumatoid arthritis occurs when the body’s immune system mistakenly attacks the cells in its joints. This leads to the release of inflammatory cytokines and enzymes that damage not just the cartilage, but also the bone. The disease does not just manifest in the joints. It produces a dangerous amount of inflammation that affects the rest of the body. Rheumatoid arthritis increases the risk of cardiovascular disease. Those with rheumatoid arthritis suffer an approximately 40% increased risk of overall mortality.13,14
In response to the immune system’s attack on joints, cells called fibroblast-like synoviocytes, which are found in the joints’ synovial fluid, release inflammatory molecules.15 Fibroblast-like synoviocytes can circumvent healthy cell turnover and instead release inflammatory molecules via a protein complex called NF-kappaB.10
In one of the new studies from the journal Inflammation, researchers tested human fibroblast-like synoviocytes in vitro, or outside of the body. The scientists used an inflammatory agent to activate the release of cytokines from the fibroblast-like synoviocytes cells. In one of the groups of cells, PQQ was also added.10 The group of cells that did not receive PQQ had increased levels of proinflammatory cytokines. The cells that received the PQQ had a decreased production of the proinflammatory cytokines. In addition, PQQ was also able to halt the activation of NF-kappaB. The researchers also noted that PQQ may be able to attenuate certain enzymes (such as matrix metalloproteinases) that degrade a protein called type-II collagen present in our joints.
In a second part of this study, the researchers tested the effects of PQQ on two groups of mice with an animal model of rheumatoid arthritis. The scientists gave intraperitoneal injections of PQQ to one group of mice but not the other. After 45 days there was a dramatic difference with the PQQ-administered mice showing remarkable protection against inflammatory degeneration. The researchers observed narrowing of space between joints, increased inflammatory cell infiltration, and cartilage damage in the group that did not receive PQQ. Due to these impressive results, the researchers hypothesized that PQQ may be helpful in the treatment of other inflammatory conditions as well.
Approximately 33% of Americans 65 and older are affected by osteoarthritis, making it the most common form of arthritis.16 It was believed that osteoarthritis was simply the result of age-related “wear and tear” of the joints, as well as the body failing to produce enough cartilage.17,18 Scientists now understand that the underlying causes of osteoarthritis are similar to that of rheumatoid arthritis.19,20
A group of researchers conducted a study to test the effects of PQQ for osteoarthritis treatment.11 In this study, human chondrocytes, cells that produce and maintain cartilage, were tested in vitro. The researchers manipulated the environment of the cells to create inflammation and mimic the effects of osteoarthritis. One group of cells received PQQ before the researchers manipulated the environment while the other group did not. The researchers observed increased levels of collagen-degrading enzymes (matrix metalloproteinase) in the group that did not receive PQQ.
One of the pivotal biomarkers for inflammation is nitric oxide. Under normal physiological conditions nitric oxide acts as an anti-inflammatory as well as a vasodilator. But in certain circumstances, overproduction can lead to inflammation.21 In the group of cells that received PQQ, there was a significant reduction in joint-degrading enzymes and nitric oxide.
In addition, the researchers tested the effects of PQQ on mice who underwent a surgical procedure to induce osteoarthritis. Prior to treatment, one group received injections of PQQ with additional injections daily. The other group did not receive any. The group that received PQQ had significantly less severe cartilage damage compared to the group that did not receive PQQ.
Practical Approaches for Arthritis
The studies thus far are laboratory models and not directly relevant to human arthritis patients. PQQ’s most impressive results have been seen in studies showing its support for mitochondrial function, cardiovascular health, and brain health.1,22,23
For those seeking natural approaches to combat arthritis, there are natural anti-inflammatory compounds in widespread use today including: undenatured type II collagen, boswellia, and curcumin.
Derived from chicken cartilage, undenatured type II collagen has robust data showing reduction in pain and increase in function in dogs, horses, and humans.24-27 Results from one study showed, in just 90 days, a 40% reduction on a pain scale for osteoarthritis patients supplementing daily with undenatured type II collagen.27
Boswellia is an Indian plant that has demonstrated potent anti-inflammatory properties. It has been shown to inhibit the pro-inflammatory enzyme 5-lipooxygenase or 5-LOX.28,29 This enzyme is responsible for facilitating the production of leukotriene, a pro-inflammatory compound that damages joints and cartilage. Boswellia has also been shown to inhibit a type of matrix metalloproteinase cartilage-degrading enzyme.30 An impressive study on osteoarthritis patients showed that daily boswellia supplementation caused a 40.1% reduction on a pain scale compared to placebo in just 30 days.31
Curcumin is the most active constituent of the turmeric root. A study tested the effects of curcumin or a nonsteroidal anti-inflammatory drug (NSAID) on 45 humans during a flare-up of rheumatoid arthritis. The researchers tested the patients’ blood for a systemic inflammatory marker called C-reactive protein and their pain score at the beginning of the study and then eight weeks afterwards. The results showed a 52% drop in C-reactive protein in the curcumin group. In the group receiving the NSAID, C-reactive protein increased by 1.5%. The NSAID group had a 42.1% improvement in pain scores, which was similar to the curcumin group, which had a 44.5% improvement (relief) in pain scores.32
PQQ has been shown to promote mitochondrial biogenesis (creation of new mitochondria), which is essential for older cells to retain youthful energy output. PQQ also protects against mitochondrial damage.2
The two new studies described in this Research Update provide preliminary data to pave the way for human trials in arthritis patients. PQQ was effective at suppressing cartilage-degrading enzymes and inflammatory markers in human cells and in the laboratory mouse model.
These findings open a pathway for clinical studies to evaluate whether PQQ can benefit osteoarthritis and rheumatoid arthritis patients. Those seeking to relieve arthritis symptoms today, without resorting to drugs, have access to a variety of low-cost nutrients with clinically validated effects.
If you have any questions on the scientific content of this article, please call a Life Extension® Wellness Specialist at 1-866-864-3027.
- Rucker R, Chowanadisai W, Nakano M. Potential physiological importance of pyrroloquinoline quinone. Altern Med Rev. 2009;14(3):268-77.
- Chowanadisai W, Bauerly KA, Tchaparian E, et al. Pyrroloquinoline quinone stimulates mitochondrial biogenesis through cAMP response element-binding protein phosphorylation and increased PGC-1alpha expression. J Biol Chem. 2010;285(1):142-52.
- Zhu BQ, Zhou HZ, Teerlink JR, et al. Pyrroloquinoline quinone (PQQ) decreases myocardial infarct size and improves cardiac function in rat models of ischemia and ischemia/reperfusion. Cardiovasc Drugs Ther. 2004;18(6):421-31.
- Tao R, Karliner JS, Simonis U, et al. Pyrroloquinoline quinone preserves mitochondrial function and prevents oxidative injury in adult rat cardiac myocytes. Biochem Biophys Res Commun. 2007;363(2):257-62.
- Guan S, Xu J, Guo Y, et al. Pyrroloquinoline quinone against glutamate-induced neurotoxicity in cultured neural stem and progenitor cells. Int J Dev Neurosci. 2015;42:37-45.
- Yamaguchi K, Sasano A, Urakami T, et al. Stimulation of nerve growth factor production by pyrroloquinoline quinone and its derivatives in vitro and in vivo. Biosci Biotechnol Biochem. 1993;57(7):1231-3.
- Jensen FE, Gardner GJ, Williams AP, et al. The putative essential nutrient pyrroloquinoline quinone is neuroprotective in a rodent model of hypoxic/ischemic brain injury. Neuroscience. 1994;62(2):399-406.
- Urakami T, Tanaka A, Yamaguchi K, et al. Synthesis of esters of coenzyme PQQ and IPQ, and stimulation of nerve growth factor production. Biofactors. 1995;5(3):139-46.
- Kong L, Yang C, Yu L, et al. Pyrroloquinoline quinine inhibits RANKL-mediated expression of NFATc1 in part via suppression of c-Fos in mouse bone marrow cells and inhibits wear particle-induced osteolysis in mice. PLoS One. 2013;8(4):e61013.
- Liu Z, Sun C, Tao R, et al. Pyrroloquinoline Quinone Decelerates Rheumatoid Arthritis Progression by Inhibiting Inflammatory Responses and Joint Destruction via Modulating NF-kappaB and MAPK Pathways. Inflammation. 2016;39(1):248-56.
- Tao R, Wang S, Xia X, et al. Pyrroloquinoline Quinone Slows Down the Progression of Osteoarthritis by Inhibiting Nitric Oxide Production and Metalloproteinase Synthesis. Inflammation. 2015;38(4):1546-55.
- Available at: https://www.cdc.gov/mmwr/preview/mmwrhtml/mm6429a2.htm. Accessed October 5, 2016.
- Radovits BJ, Fransen J, Al Shamma S, et al. Excess mortality emerges after 10 years in an inception cohort of early rheumatoid arthritis. Arthritis Care Res (Hoboken). 2010;62(3):362-70.
- Khan F, Galarraga B, Belch JJ. The role of endothelial function and its assessment in rheumatoid arthritis. Nat Rev Rheumatol. 2010;6(5):253-61.
- Bartok B, Firestein GS. Fibroblast-like synoviocytes: key effector cells in rheumatoid arthritis. Immunol Rev. 2010;233(1):233-55.
- Available at: http://www.cdc.gov/arthritis/basics/osteoarthritis.htm. Accessed October 7, 2016.
- Pearle AD, Warren RF, Rodeo SA. Basic science of articular cartilage and osteoarthritis. Clin Sports Med. 2005;24(1):1-12.
- Aigner T, Rose J, Martin J, et al. Aging theories of primary osteoarthritis: from epidemiology to molecular biology. Rejuvenation Res. 2004;7(2):134-45.
- Wang Q, Rozelle AL, Lepus CM, et al. Identification of a central role for complement in osteoarthritis. Nat Med. 2011;17(12):1674-9.
- Ballanti E, Perricone C, Greco E, et al. Complement and autoimmunity. Immunol Res. 2013;56(2-3):477-91.
- Sharma JN, Al-Omran A, Parvathy SS. Role of nitric oxide in inflammatory diseases. Inflammopharmacology. 2007;15(6):252-9.
- Harris CB, Chowanadisai W, Mishchuk DO, et al. Dietary pyrroloquinoline quinone (PQQ) alters indicators of inflammation and mitochondrial-related metabolism in human subjects. J Nutr Biochem. 2013;24(12):2076-84.
- Nakano M, Ubukata K, Yamamoto T, et al. Effect of pyrroloquinoline quinone (PQQ) on mental status of middle-aged and elderly persons. FOOD Style 21. 2009;13(7):50-3.
- Deparle LA, Gupta RC, Canerdy TD, et al. Efficacy and safety of glycosylated undenatured type-II collagen (UC-II) in therapy of arthritic dogs. J Vet Pharmacol Ther. 2005;28(4):385-90.
- D’Altilio M, Peal A, Alvey M, et al. Therapeutic Efficacy and Safety of Undenatured Type II Collagen Singly or in Combination with Glucosamine and Chondroitin in Arthritic Dogs. Toxicol Mech Methods. 2007;17(4):189-96.
- Gupta RC, Canerdy TD, Skaggs P, et al. Therapeutic efficacy of undenatured type-II collagen (UC-II) in comparison to glucosamine and chondroitin in arthritic horses. J Vet Pharmacol Ther. 2009;32(6):577-84.
- Crowley DC, Lau FC, Sharma P, et al. Safety and efficacy of undenatured type II collagen in the treatment of osteoarthritis of the knee: a clinical trial. Int J Med Sci. 2009;6(6):312-21.
- Safayhi H, Rall B, Sailer ER, et al. Inhibition by boswellic acids of human leukocyte elastase. J Pharmacol Exp Ther. 1997;281(1):460-3.
- Safayhi H, Sailer ER, Ammon HP. Mechanism of 5-lipoxygenase inhibition by acetyl-11-keto-beta-boswellic acid. Mol Pharmacol. 1995;47(6):1212-6.
- Sengupta K, Krishnaraju AV, Vishal AA, et al. Comparative efficacy and tolerability of 5-Loxin and aflapin against osteoarthritis of the knee: a double blind, randomized, placebo controlled clinical study. Int J Med Sci. 2010;7(6):366-77.
- Vishal AA, Mishra A, Raychaudhuri SP. A double blind, randomized, placebo controlled clinical study evaluates the early efficacy of aflapin in subjects with osteoarthritis of knee. Int J Med Sci. 2011;8(7):615-22.
- Chandran B, Goel A. A randomized, pilot study to assess the efficacy and safety of curcumin in patients with active rheumatoid arthritis. Phytother Res. 2012;26(11):1719-25.