Supplementing Quercetin for Neurotrophic and Senolytic Effects

Click here to watch the companion video to this blog post.


My favorite quercetin supplements:

  1. Thorne Research's Phytosomal Quercetin, which you can find here.

  2. Double Wood's very cheap product, which you can find here.

  3. BulkSupplements' product, which you can find here.

A comparison of these products' prices per mg of quercetin can be found at this end of this blog post.


FLAVONOIDS


1. Flavonoids are categorized into flavonols, flavones, flavanones, catechins, and anthocyanidins[1].

a. Flavonols include quercetin, fisetin, galangin, kaempferol, myricetin, quercitrin, and rutin.

2. Quercetin (3,3’,4’,5,7-pentahydroxylflavone) is the most prevalent flavonoid in food, followed by kaempferol[2].

3. Quercetin is found as quercetin aglycone in food and quercetin rutinoside (also called rutin) in tea, where aglycone is absorbed more quickly and uniformly by people[3].

4. The richest quercetin containing foods in descending order are elderberries, red onions, white onions, cranberries, green hot peppers, kale, blueberries, and red apples[4].


FREE RADICALS


1. Quercetin’s various metabolites have differential ability to scavenge free radicals[5][6].

2. Using human leukemia cells stimulated by lipopolysaccharides, quercetin was shown to inhibit reactive oxygen and nitrogen species with a higher reduction potential than curcumin at three different PHs and a total antioxidant capacity (TAC) 3.5x more powerful than curcumin[7].

3. On the DPPH assay, quercetin’s ability to scavenge free radicals is worse than EGCG and tied with epicatechin gallate (ECG), though it is superior to myricetin and kaempferol[8].

4. Quercetin’s ORAC score is lower than kaempferol and myricetin (and all of the catechins, which are led by epicatechin)[9].

5. In the FRAP and ABTS assays, quercetin is a better free radical scavenger than alpha-tocopherol[10].

6. It is less effective than epigallocatechin gallate (EGCG) at inhibiting DNA damage but more capable at producing DNA damage (at high concentrations)[11].


THE BRAIN


1. Nanoparticles have been developed to deliver quercetin[12][13].

2. Quercetin reduced oxidative stress by inhibiting inducible nitric oxide synthase protein expression and mitochondrial superoxide radicals and reduced the expression of IL-6, IL-1beta, and TNF-alpha in microglia treated with the Parkinsonian toxin MPP[14].

3. In rodent models of cerebral ischemia (hypoxic brain), quercetin protects neurons from apoptosis likely via upregulated of TrkB and BDNF[15].

4. Higher doses of quercetin increase BDNF mRNA in the rodent hippocampus[16].

5. In a model of polychlorinated biphenyl (PCBs) toxicity, PCB-induced suppression of rodent steroidogenesis was attenuated by quercetin. Quercetin also attenuated reductions on estrogen receptors in the hippocampus and BDNF signaling[17].

6. In a model of dimethylhydrazine-induced colorectal cancer, quercetin (with exercise) reduced tumor incidence, improved depressive symptoms, and upregulated BDNF[18].

7. In a model of lipopolysaccharide-induced rodent depression (and anxiety[19]), quercetin could attenuated LPS-induced downregulation of BDNF[20].

8. In a rodent model of oxidative injury to a mother, quercetin given to the mother improved BDNF signaling in offspring[21].

9. In rodents, quercetin can prophylactically protect rodents from memory impairments due to hypoxia[22].

10. In a rodent model of transgenic Parkinsonian mice, it appears that quercetin attenuates the progression of the disease[23].

11. Pre-treatment with quercetin limits dopaminergic neuron loss from the MPP toxin[24].

12. Quercetin improved BDNF expression after a spinal chord injury to rodents[25].

13. In a transgenic rodent model of Alzheimer’s, quercetin was more effective at attenuating the pathology of beta amyloid plaques when the rodents were given less vitamin D[26].

14. Quercetin’s neuroprotective element may require greater concentrations of the flavonoid than myricetin[27].

15. Chronic unpredicted stress (CUS) produces cognitive dysfunction and insulin resistance in rodents. Quercetin upregulates GLUT4 expression in the hippocampus and alleviates memory dysfunction[28].

16. Quercetin protects against dopaminergic dysfunction due to cadmium toxicity in a rodent model[29].

17. Quercetin and its glucosides (including rutin) affect alpha7 nicotinic cholinergic receptor ion currents. Quercetin increases them and rutin most potently decreases them[30].

18. Quercetin can attenuate GABA-A alpha5 receptor downregulation due to glutamate excitotoxicity (as seen here in a mouse seizure model with kainic acid[31]).


CANCER


1. Quercetin is selectively cytotoxic against cancers cells of blood, brain, lung, uterine, skin, and salivary glands[32].

a. It is compared to other flavonoids in this paper[33].

2. Quercetin aglycone interacts with the aryl hydrocarbon receptor and modulates MEK/ERK and Nrf2/keap1 pathways[34].

3. Quercetin is also thought to reduce the phosphorylation of activated heat shock protein transcription factor (HSF)[35], allowing it to experience proteolytic degradation, thereby reducing heat shock protein expression[36]. Heat shock proteins are overexpressed in tumors[37].

4. Quercetin inhibits breast cancer stem cell development[38].

5. Quercetin’s cytotoxicity to human prostate and skin cancer cell lines is enhanced with ultrasound use[39].

6. Quercetin sensitizes prostate cancer cells to chemotherapeutic medicines, such as docetaxel[40].

7. Quercetin improves apoptosis in human pancreatic cancer cell lines[41].

8. Quercetin suppresses the development of metastatic osteosarcoma cancer cells[42].

9. Quercetin nanoparticles exert an anti-tumor effect on hepatocellular carcinoma cells by inhibiting NFkB, COX-2, and Akt signalling[43].

a. Quercetin is also being investigated as a treatment for primary liver tumors (PLTs), due to its competitive inhibition of the glucose transporter 1 (GLUT1), which is upregulated in PLT[44].


THE LIVER


1. Quercetin upregulates the expression of metallothioneins, which in turn may phosphorylate JNK, p38, and PI3K/Akt, and may enhance Nrf2 activity. This produces a protective effect over hepatocytes[45].

2. In a rodent model of T2D-induced NAFLD, quercetin improved inflammatory measures, bile acid measures, and reduced fat retention in the liver[46].

3. Quercetin has imp