Science on Potential Benefits of Fulvic & Humic Acid

Fulvic acid is a vital natural compound found in soil and plants, but its presence in modern food has diminished due to changes in farming practices. This decline is impacting human health as fulvic acid plays a crucial role in nutrient absorption and overall well-being.
Key points about fulvic acid:
1. Origin and Importance: Fulvic acid is created by microbes in fertile soil, breaking down organic matter and enriching it with nutrients. It has historically been used for its health benefits.
2. Nutrient Absorption: Fulvic acid enhances the body's absorption of vitamins and minerals, making it a critical component for overall health.
3. Health Benefits: Fulvic acid has numerous health benefits, including anti-inflammatory and anti-allergy effects, improvements in skin conditions, enhanced wound healing, antioxidant properties, anti-aging benefits, improved gut health, and more.
4. Historical Use: In Ayurvedic medicine, fulvic acid, knitric oxidewn as Shilajit, has been used for over 3,000 years for its immune-modulating, antioxidant, and other health benefits.
5. Depletion from Food: Modern Farming practices, which rely heavily on chemical fertilizers and pesticides, havedisrupted the natural soil ecosystem and reduced fulvic acid content in food.
6. Nature's Answer: Fulvic acid cannot be synthesized in a lab; it relies on the complex interplay of microbes and fertile soil. It is an essential component of humus, the end product of organic matter decomposition.
7. Low Nutrient Absorption: Many people suffer from low nutrient absorption despite consuming a good diet and supplements. Fulvic acid helps address this issue by delivering nutrients effectively to cells.
8. Electrolyte and Antioxidant Properties: Fulvic acid also acts as an electrolyte, increasing cellular voltage and helping cells function optimally. It can recharge cells and remove waste products and toxins.
9. Skin Health: Fulvic acid has anti-inflammatory and antimicrobial properties, making it beneficial for various skin conditions, including eczema. It can also offer potential benefits in cancer prevention and brain health.
10. Supplementation: To ensure an adequate intake of fulvic acid, supplementation is recommended. It is available in liquid, powder, and capsule forms, with liquid forms often considered more bioavailable. When choosing a supplement, consider factors like the source, extraction process, and purity
11. Mineral Deficiency: Fulvic acid is rich in bioavailable minerals and trace elements that are essential for various biochemical processes in the body. Mineral deficiencies are widespread, and fulvic acid can help combat this issue by delivering these nutrients effectively to cells.
12. Role in Agriculture: Fulvic acid is nitric oxidet only beneficial for human health but also plays a crucial role in agriculture. It can improve soil quality, enhance plant growth, and increase crop yields, making it valuable for sustainable farming practices.
13. Electrical Potential: Fulvic acid can increase cellular voltage, promoting cellular health and vitality. By ensuring that cells are adequately charged, it supports various biochemical processes that contribute to overall wellness.
14. Skin Benefits: Fulvic acid has been shown to have positive effects on the skin. It can reduce inflammation, relieve itching, and improve the appearance of skin conditions like eczema. Its antimicrobial properties make it useful for treating skin infections.
15. Cancer Prevention: Some studies suggest that fulvic acid and related humic substances may havecancer-preventive properties. They can combat cancer risk factors like free radicals, toxins, and inflammation, potentially reducing the likelihood of cancer development.
16. Brain Health: Fulvic acid has shown promise in protecting against cognitive impairment and neurodegenerative diseases. It may inhibit the formation of tau protein tangles associated with Alzheimer's disease, making it a potential ally in brain health.
17. Natural Sources: While fulvic acid can be obtained from organically grown vegetables, it is challenging to guarantee sufficient intake from diet alone due to modern farming practices. Organic unsulphured blackstrap molasses can also serve as a source of fulvic acid.
18. Supplementation Benefits: Fulvic acid supplements are available in various forms, with liquid preparations often being the preferred choice for better bioavailability. They can be easily incorporated into daily health routines.
19. Consumer Considerations: When selecting a fulvic acid supplement, it's essential to consider factors like the source, extraction method, potency, and packaging. Ensuring that the product meets quality standards is crucial for reaping its full benefits.
20. Overall Wellness: Fulvic acid is being recognized as a missing piece in many people's health regimens. Whether you're addressing chronic diseases, infections, or seeking anti-aging strategies, incorporating fulvic acid into your daily routine may help enhance nutrient absorption, detoxification, and cellular health.
[i] Acharya, S. B.; Frotan, M. H.; Goel, R. K.; Tripathi, S. K.; Das, P. K. Pharmacological actions of shilajit. Indian J. Exp. Biol. 1988, 26, 775-777.)
[ii] Agarwal SP, Khanna R, Karmarkar R, Anwer MK, Khar RK. Shilajit: a review. Phytother Res. 2007 May;21(5):401-5. doi: 10.1002/ptr.2100. Review. PubMed PMID: 17295385.
[iii] Anisimov, V. E.; Shakirzyanova, R. M. Application of mumie in therapeutic practice. Kazan. Med. Zhurn. 1982, 2, 65-68.
[iv] Bhavsar, S.K.; Thaker, A.M.; Malik, J.K. Chapter 51 - Shalajit, Nutraceuticals, Efficacy, Safety and Toxicity 2016, Pages 707-716 https://doi.org/10.1016/B978-0-12-802147-7.00051-6
[v] Carrasco-Gallardo C, Guzmán L, Maccioni RB. Shilajit: a natural phytocomplex with potential procognitive activity. Int J Alzheimers Dis. 2012;2012:674142. doi:10.1155/2012/674142.
[vi] Chang Q, Lu Z, He M, Gao R, Bai H, Shi B, Shan A. Effects of dietary supplementation of fulvic acid on lipid metabolism of finishing pigs. J Anim Sci. 2014 Nov;92(11):4921-6. doi: 10.2527/jas.2014-8137. PubMed PMID: 25349342.
[vii] Cheam, V.; Gamble, D. Metal-Fulvic Acid Chelation Equilibrium in Aqueous NaNO3 Solution. Hg, Cd, Cu Fulvate Complexes. Canadian Journal of Soil Science, 1974, 54(4): 413-417, https://doi.org/10.4141/cjss74-055
[viii] Chopra, N.; Chopra, R.; Handa, K.; Kapoor, D. In Indigenous Drugs of India. Calcutta, India: U.N. Dhar & Sons; 1958.
[ix] Cornejo A, Jiménez JM, Caballero L, Melo F, Maccioni RB. Fulvic acid inhibits aggregation and promotes disassembly of tau fibrils associated with Alzheimer's disease. Journal of Alzheimer's Disease. 2011;27(1):143-153. doi: 10.3233/JAD-2011-110623.
[x] Dizman, M.; Tutar, Karaman, A.; Turan. Humik Maddelerin İlaç Olarak Kullanımı ve İnsan Sağlığına Etkileri. Sakarya Üniversitesi, Fen Edebiyat Fakültesi Dergisi. 2012. 14. 25-33.
[xi] Gandy J. J., Meeding J. P., Snyman J. R., Van Rensburg C. E. (2012). Phase 1 clinical study of the acute and subacute safety and proof-of-concept efficacy of carbohydrate-derived fulvic acid. Clin. Pharmacol. 4, 7-11. 10.2147/CPAA.S25784
[xii] Chien et al. Fulvic acid attenuates homocysteine-induced cyclooxygenase-2 expression in human monocytes. BMC Complementary and Alternative Medicine (2015) 15:61 DOI 10.1186/s12906-015-0583-x
[xiii] Fujita, K.; Nagamine, Y.; Ping, X.; Taniguchi, M. Mode of Action of Anhydrofulvic Acid against Candida utilis ATCC 42402 under Acidic Condition. J Antibiot (Tokyo). 1999 Jul;52(7):628-34. doi: 10.7164/antibiotics.52.628. PubMed PMID: 10513842.
[xiv] Gandy JJ, Snyman JR, van Rensburg CE. Randomized, parallel-group, double-blind, controlled study to evaluate the efficacy and safety of carbohydrate-derived fulvic acid in topical treatment of eczema. Clin Cosmet Investig Dermatol. 2011;4:145-148. doi: 10.2147/CCID.S23110
[xv] Ghosal S. Chemistry of shilajit, an immunomodulatory Ayurvedic rasayan. Pure and Applied Chemistry. 1990;62(7):1285-1288.
[xvi] Ghosal, S.; Lal, J.; Jaiswal, A. K.; Bhattacharya, S. K. Effects of shilajit and its active constituents on learning and memory in rats. Phytother. Res. 1993, 7, 29-34.
[xvii] Huang WS, Yang JT, Lu CC, et al. Fulvic Acid Attenuates Resistin-Induced Adhesion of HCT-116 Colorectal Cancer Cells to Endothelial Cells. Int J Mol Sci. 2015;16(12):29370-29382. Published 2015 Dec 9. doi:10.3390/ijms161226174.
[xviii] Iglesias A, López R, Gondar D, Antelo J, Fiol S, Arce F. Effect of pH and ionic strength on the binding of paraquat and MCPA by soil fulvic and humic acids. Chemosphere. 2009 Jun;76(1):107-13. doi: 10.1016/j.chemosphere.2009.02.012. Epub 2009 Mar 9. PubMed PMID: 19269671.
[xix ] Iubitskaia NS, Ivanov EM. [Sodium humate in the treatment of osteoarthrosis patients]. Vopr Kurortol Fizioter Lech Fiz Kult. 1999 Sep-Oct;(5):22-4. PubMed PMID: 10598525.
[xx] Jayasooriya RGPT, Dilshara MG, Kang CH, Lee S, Choi YH, Jeong YK, Kim GY. Fulvic acid promotes extracellular anti-cancer mediators from RAW 264.7 cells, causing to cancer cell death in vitro. Int Immunopharmacol. 2016 Jul;36:241-248. doi: 10.1016/j.intimp.2016.04.029. Epub 2016 May 11. PubMed PMID: 27177083.
[xxi] Kinoshita, H.; Kinoshita, M.; Takahashi, A.; Yuasa, S.; Fukuda, K. Effect of fulvic acid on ultraviolet induced skin aging. The effect of fulvic acid on fibroblasts and matrix metalloproteinase. Nishinihon Journal of Dermatology. 2012; 74(4):427-431.
[xxii] Klocking, R.; Helbig, B. Medical aspects and applications of humic substances. Biopolymers for Medical and Pharmaceutical Applications. 2005 Willey-VCH Verlag GmbH & Co. KGaA, Weinheim, ISBN: 3-527-31154-8.
[xxiii] Marova I, Kucerik J, Duronova K, Mikulcova A, Vlckova Z. Antimutagenic and/or genotoxic effects of processed humic acids as tested upon S. cerevisiae D7. Environ Chem Lett 2011;9:229-33.
[xxiv] Meena H, Pandey HK, Arya MC, Ahmed Z. Shilajit: A panacea for high-altitude problems. Int J Ayurveda Res. 2010;1(1):37-40. doi:10.4103/0974-7788.59942.
[xxv] Motojima H., Yamada P., Han J., Ozaki M., Shigemori H., Isoda H. Properties of fulvic acid extracted from excess sludge and its inhibiting effect on beta-hexosaminidase release. Biosci. Biotechnol. Biochem. 2009;73:2210-2216. doi: 10.1271/bbb.90316.
[xxvi] Quin, Y.; Zhang, M.; Dai, W. Antidiarrhoeal mechanism study of fulvic acids based on molecular weight fractionation. Fitoterapia. 2019, 137, doi: 10.1016/j.fitote.2019.104270.
[xxvii] Pant, K.; Singh, B.; Thakur, N. Shilajit: A Humic Matter Panacea for Cancer. International Journal of Toxicological and Pharmacological Research 2012; 4(2): 17-25.
[xxviii] Peña-Méndez EM, Havel J, Patočka J. Humic substances - compounds of still unknown structure: applications in agriculture, industry, environment, and biomedicine. J Appl Biomed. 2005;3(1):13-24. doi: 10.32725/jab.2005.002.
[xxix] Sabi R., Vrey P., Van Rensburg C. E. (2012). Carbohydrate-derived fulvic acid (CHD-FA) inhibits carrageenan-induced inflammation and enhances wound healing: efficacy and toxicity study in rats. Drug Dev. Res. 73, 18-23. 10.1002/ddr.20445.
[xxx] Schepetkin, I. A.; Khlebnikov, A. I.; Ah, S. Y.; Woo, S. B.; Jeong, C. S.; Klubachuk, O. N.; Kwon, B. S. Characterization and Biological Activities of Humic Substances from Mumie J. Agric. Food Chem. 2003, 51, 5245−5254.
[xxxi] Schepetkin, I.; Khlebnikov, A.; Kwon, B. Medical drugs from humus matter: Focus on mumie. Drug Development Research. 2002;57:140-159. doi: 10.1002/ddr.10058.
[xxxii] Sherry L., Jose A., Murray C., Williams C., Jones B., Millington O., et al. (2012). Carbohydrate derived fulvic acid: an in vitro investigation of a novel membrane active antiseptic agent against Candida albicans biofilms. Front. Microbiol. 3:116. 10.3389/fmicb.2012.00116.
[xxxiii] Sherry L., Millhouse E., Lappin D. F., Murray C., Culshaw S., Nile C. J., et al. (2013). Investigating the biological properties of carbohydrate derived fulvic acid (CHD-FA) as a potential novel therapy for the management of oral biofilm infections. BMC Oral Health 13:47. 10.1186/1472-6831-13-47.
[xxxiv] Tachibana Y, Hiribe S, and Tawa R, Trace Nutr. Res. (in Japanese), 23, 104-108 (2004).
[xxxv] Trivedi N A, Mazumdar B, Bhatt J D, Hemavathi K G. Effect of shilajit on blood glucose and lipid profile in alloxan-induced diabetic rats. Indian J Pharmacol 2004;36:373-6.
[xxxvi] van Rensburg C.E., van Straten A., Dekker J. An in vitro investigation of the antimicrobial activity of oxifulvic acid. J. Antimicrob. Chemother. 2000;46:853-854. doi: 10.1093/jac/46.5.853.
[xxxvii] van Rensburg C.E., Malfeld S.C.K., Dekker J. Topical application of oxifulvic acid suppresses the cutaneous immune response in mice. Drug Dev. Res. 2001;53:29-32. doi: 10.1002/ddr.1166.
[xxxviii] Wilson E., Rajamanickam G. V., Dubey G. P., et al. Review on shilajit used in traditional Indian medicine. Journal of Ethnopharmacology. 2011;136(1):1-9. doi: 10.1016/j.jep.2011.04.033.
[xxxix] Winkler J, Ghosh S. Therapeutic Potential of Fulvic Acid in Chronic Inflammatory Diseases and Diabetes. J Diabetes Res. 2018;2018:5391014. Published 2018 Sep 10. doi:10.1155/2018/5391014.
[xl] Yamada P, Isoda H, Han JK, Talorete TP, Abe Y. Inhibitory effect of fulvic acid extracted from Canadian sphagnum peat on chemical mediator release by RBL-2H3 and KU812 cells. Biosci Biotechnol Biochem. 2007 May; 71(5):1294-305. https://www.jstage.jst.go.jp/article/bbb/71/5/71_60702/_article doi:
[xli] Yudina, N. V.; Pisareva, S. I.; Saratikov, A. S. Antiulcerogenic activity of phenol compounds of peat. Khim. Rastit. Sirya 1998, 4, 29-32.)
[xlii] Yuanyuan, J. I.; Zhang, A.; Chen, X.; Che, X.; Zhou, K.; Wang, Z. Sodium humate accelerates cutaneous wound healing by activating TGF-β/Smads signaling pathway in rats. Acta Pharm Sin B. 2016; 6(2):132-140. doi: 10.1016/j.apsb.2016.01.009.
[xliii] Zhang X.F., Yang G., Dong Y., Zhao Y.Q., Sun X.R., Chen L., Chen H.B. Studies on the binding of fulvic acid with transferrin by spectroscopic analysis. Spectrochim. Acta A Mol. Biomol. Spectrosc. 2015;137:1280-1285. doi: 10.1016/j.saa.2014.09.010.
[xliv] Zhao Y, Paderu P, Delmas G, Dolgov E, Lee MH, Senter M, Park S, Leivers S, Perlin DS. Carbohydrate-derived fulvic acid is a highly promising topical agent to enhance healing of wounds infected with drug-resistant pathogens. J Trauma Acute Care Surg. 2015 Oct;79(4 Suppl 2):S121-9. doi: 10.1097/TA.0000000000000737. PubMed PMID: 26406424.

Using Fulvic & Humic acid to detox Graphene Oxide

The results and discussion section of the provided text describe the findings of an experiment related to the adsorption and bioaccumulation of PFOS (Perfluorooctanesulfonic acid) in fish in the presence of GO (Graphene Oxide) and FA (Fulvic Acid). Here's a summary of the key findings and discussions:
Adsorption of PFOS on GO with/without FA:
• PFOS exhibited strong sorption affinity for GO due to interactions between the hydrophobic carbon chain of PFOS and the basal plane of GO.
• FTIR spectra confirmed the presence of oxygen-containing functional groups on GO's surface, allowing hydrogen bonds to form between PFOS and GO.
• The presence of FA significantly suppressed PFOS adsorption on GO. FA interacted with the O-containing functional groups in GO, competing for adsorption sites.
• Desorption studies revealed strong interactions between PFOS and GO, resulting in desorption hysteresis.
Effects of GO and FA on the Bioaccumulation of PFOS in Fish:
• In the presence of GO, PFOS bioaccumulation in fish tissues was significantly enhanced, particularly in the liver, kidney, and intestine.
• The presence of GO altered the uptake routes of PFOS, increasing its uptake via gills and intestines.
• GO acted as a vehicle, potentially circulating from the intestine to the liver and blood, promoting PFOS accumulation.
• The addition of FA reduced PFOS bioaccumulation in the presence of GO. FA led to flocculation and reduced the bioaccessibility of PFOS in the intestine.
• The uptake mechanism of PFOS involved both gill absorption and ingestion of GO. The relative contribution of these routes depended on exposure time and the presence of FA.
In Vitro Simulated Digestion and Absorption Behaviors:
• In vitro digestion experiments showed that GO could penetrate cell membranes and circulate in body fluids, enhancing PFOS bioaccessibility.
• The presence of FA reduced the bioaccessibility of PFOS in the intestine by causing GO flocculation and reduced PFOS absorption.
Uptake Mechanism of PFOS in Fish:
• Gill absorption and ingestion of GO were the primary routes of PFOS uptake in fish.
• GO's flexible nature allowed it to occupy absorption sites and block gill passages over time, reducing gill absorption.
• Ingestion of GO and subsequent absorption via the intestine played a more significant role in blood accumulation of PFOS.
• The presence of FA suppressed PFOS absorption via the intestine, reducing its bioavailability.
Overall, this study suggests that GO can significantly influence the bioaccumulation of PFOS in fish, with the presence of FA modulating these effects through interactions with GO and PFOS.
Qiang, L., Chen, M., Zhu, L., Wu, W., & Wang, Q. (2016). Facilitated Bioaccumulation of Perfluorooctanesulfonate in Common Carp (Cyprinus carpio) by Graphene Oxide and Remission Mechanism of Fulvic Acid. Environmental Science & Technology, 50(21), 11627–11636. doi:10.1021/acs.est.6b02100

This study demonstrated the potential of humic acid to prevent toxicity in aquatic life
• Graphene oxide (GO), synthesized using the Hummers' method, obtained from Nanjing XFNANO Materials Tech Co., Ltd., China.
• Humic acid sodium salt (HA) used as a natural organic matter (NOM) model, purchased from Sigma-Aldrich.
• Various chemical reagents of spectral or analytical grade.
GO particles and HA were dispersed in ultrapure water to prepare stock solutions at final concentrations of 2 g L−1 for GO and 1 g L−1 for HA, respectively. These stock solutions were sonicated for 30 minutes before being diluted to different exposure concentrations using the relevant culture medium for the test organisms (S. obliquus and D. magna).
Characterization of GO and GO-HA:
• The size and charge distribution of GO (10 mg L−1) in ultrapure water and various concentrations of HA (5, 10, 25 mg L−1) were determined using a Zetasizer Nano analyzer (Nano-ZS90, Malvern, U.K.).
• The absorption wavelength of GO and GO-HA in the range of 200–800 nm was determined using a UV spectrophotometer (V-560, Jasco, Japan).
• The degree of carbon structure defects and the composition of chemical bonds in GO and GO-HA were analyzed using a Raman spectrometer (DXR, Thermo Fisher, USA) and Fourier-transform infrared spectrometer (FT-IR, 6700, Thermo Fisher, USA), respectively.
Toxicity Tests:
Culture of Test Organisms:
For the algae S. obliquus:
• Obtained from the Institute of Hydrobiology of the Chinese Academy of Sciences.
• Cultured in an illumination incubator at a constant temperature of 25.0 ± 0.5 °C with a 12:12 h light-dark cycle.
For D. magna:
• Originally obtained from Dalian Ocean University.
• Continuously cultured in the laboratory at a constant temperature of 20 ± 1 °C with a 16:8 h light-dark cycle.
Acute Toxicity Test:
For S. obliquus:
• Algae cells in the exponential growth phase (2 × 105 cell mL−1) exposed to various concentrations of GO (5, 10, 20, 40, and 80 mg L−1) in a 100 mL test solution.
• Cell density measured at 0 h and 72 h with a UV spectrophotometer at 690 nm. Chl-a content determined based on ethanol extraction method.
For D. magna:
• Neonates (less than 24 hours old) exposed to different GO concentrations (50.0, 65.0, 84.5, 110.0, and 143.0 mg L−1) in a 50 mL test solution.
• 48-hour mortality rate calculated.
Chronic Toxicity Test:
• One D. magna neonate (less than 24 hours old) exposed to sublethal concentrations of GO (0, 0.01, 0.1, 1.0, 10, 50 mg L−1) in ten replicates.
• Exposure mediums renewed every 48 hours, and food (S. obliquus) added daily.
• After 21 days of exposure, various parameters, including mortality rate, time to produce the first brood, offspring number of first brood, offspring number of the most productive brood, and total number of offspring, were calculated.
Oxidative Damage Test:
For S. obliquus:
• The intracellular reactive oxygen species (ROS) content measured using 2′,7′-dichlorofluorescin-diacetate (DCFH-DA).
• Superoxide dismutase (SOD) and catalase (CAT) activity assays performed.
For D. magna:
• ROS levels and activities of SOD and CAT analyzed.
Scanning Electron Microscopy (SEM):
• Cell morphology of algae after exposure to GO observed using SEM.
Light Microscopy Observation:
• Ingestion of GO in the bodies of D. magna observed using a light microscope.
Statistical Analysis:
• All statistical analyses conducted using Origin 8.0 and SPSS 18.0. Data expressed as mean ± SD. One-way ANOVA with Tukey's test used to test for significant differences (p < 0.05).

This study systematically investigated the multilevel toxicity (acute toxicity, chronic toxicity, and oxidative damage) of GO to S. obliquus Fig. 4. SEM images of algae cells exposed to GO with or without HA. Note: Black arrows indicate the scattered debris of nanomaterials; black circles indicate the envelopment of cells by the nanomaterials. Y. Zhang et al. / Science of the Total Environment 649 (2019) 163–171 169 and D. magna, as well as the effect of HA coexposure on their toxicities. Our results showed that S. obliquus was more sensitive to the toxicity of GO than D. magna. HA could significantly mitigate the acute toxicity and oxidative damage of GO to S. obliquus and D. magna as well as alleviate the chronic toxicity of GO to D. magna. HA could also mitigate the surface envelopment in S. obliquus and decrease the accumulation of GO in the body of D. magna. Our findings aid in understanding the biotoxicity and ecological risks of GO with the consideration of its potential interaction with NOM, avoiding an overestimation of the risks of GO in the natural aquatic environment.

Zhang, Y., Meng, T., Shi, L., Guo, X., Si, X., Yang, R., & Quan, X. (2018). The effects of humic acid on the toxicity of graphene oxide to Scenedesmus obliquus and Daphnia magna. Science of The Total Environment. doi:10.1016/j.scitotenv.2018.08.2
 

Humic & Fulvic Acid as an Anti-Viral Agent

This is absolutely incredible information that shows the power of humic acid as an antiviral agent.
Research shows that humic acid, of which fulvic acid forms part, binds so strongly to viruses that it can actually displace them from a cell surface. In vitro studies have shown, for example, that if you allow herpes simplex viruses to attach to host cells and then add humic acid to the solution, it will displace viruses from infected cell surfaces. That is, humic acid has a greater affinity for the virus than the virus does for the host cell. Thus, humic acid can actually displace a virus even after it has attached itself to the surface of a cell.
This is taken directly from an interview with Richard J Laub, MS, PhD, CChem, FRSC, and was conducted by Focus Allergy Research Group.
“Focus: How exactly does humic acid bind to a virus?
RJL: Binding occurs through hydrogen bonding. Electropositive atoms attract electronegative atoms. These are the same forces that hold DNA together. What is remarkable is that humic acid, with its many kinds of functional groups, binds more strongly to viruses than do our own cells. Certain humic acids from certain soil deposits are essentially like a really, really sticky piece of Velcro. Viruses also have really sticky sites—that’s how they manage to bind to a host cell. When these two very sticky pieces of Velcro come together they bind together very strongly.

Focus: Can you explain what a virus does once it attaches to a cell receptor?

RJL: It essentially pokes a hole in the cell, and injects either its RNA or DNA–its genomic material–into the cell. At that point the virus has essentially spent itself, but the viral material inside the cell uses the cell’s machinery to create more viruses, which then leave the cell and go on to bind to and infect other cells.

Focus: What happens to a virus when it binds to humic acid instead of a cell surface?

RJL: Humic acid essentially neutralises a virus’s chemical “stickiness”. Doing so in turn prevents the virus from reproducing since it can no longer attach (“fuse”) to the surface of a host cell. The immune system can then begin to eliminate the virus (largely through the action of macrophages). Also, viruses don’t live forever: if not allowed to reproduce, influenza viruses, for example, die out in 36-48 hours.

Focus: What happens if viruses have already attached to your cells? Can humic acid help?

RJL: Humic acid binds so strongly to viruses that it can actually displace them from a cell surface. In vitro studies have shown, for example, that if you allow herpes simplex viruses to attach to host cells and then add humic acid to the solution, it will displace viruses from infected cell surfaces. That is, humic acid has a greater affinity for the virus than the virus does for the host cell. Thus, humic acid can actually displace a virus even after it has attached itself to the surface of a cell.
Focus: That’s quite amazing—that this natural substance can displace viruses that have already locked onto cells. Is this true of any humic acid from around the world?

RJL: No. Humic acid varies dramatically from site to site. Humic acids from different deposits have very different physicochemical properties. Just like coal—the coal from South Africa is very different in makeup than the coal from Birmingham in Britain. For instance, one of the better-known humic acid deposits in the United States occurs in the state of New Mexico, where humic acid is mined for agriculture–as a fertiliser–and also for the petroleum industry as a drilling mud additive. From an agricultural standpoint New Mexico humic acid is great, but it is not very effective at combating human viruses. A lot of the research I carried out in the early days was simply obtaining samples of humic acid from around the world and testing them to see which ones were efficacious against human viral disease. Remember, humic acid is the result of composted organic matter that is 50-100,000 years old, and that can be found almost anywhere—places where there are freshwater deposits and vegetation living around freshwater lakes, other places where there are saltwater deposits and decomposed organic matter at the edge of marine environments. Some humic acids come from decomposed forests, others from marshes, peat bogs, or scrub-brush. Any plant can be composted into humic acid, but the enormous variety of plant life means that each source of humic acid is unique.

Focus: Once you found the ideal antiviral humic acid, what did you do?

RJL: The next challenge was to purify and sterilise it without degrading it. When you first dig humic acid out of the ground it is dark-brown or even black. Shilajit is a very crude form of humic acid that has been used around the world for hundreds (if not thousands) of years. The most familiar form of humic acid looks like coal, and is sometimes called leonardite or brown coal—though it isn’t actually coal. So, the challenge was to extract the humic acid without damaging it. Methodologies suitable for sterilisation of the final processed product also took very considerable research and development. (The original microbes that created the humus are of course long since dead, but other bacteria and moulds flourish in such soil deposits.) Overall, ten solid years of research and development were required to identify a quality source of humic acid that could also be purified and sterilised without diminishing its effectiveness as a human antiviral agent.”

Impact of Humic Acid on Leukemia Cells

In this study, researchers investigated the effects of humic acid (Humic Acid), a phenitric oxidelic polymer, on human premyelocytic leukemia HL-60 cells. They found that treatment with different concentrations of Humic Acid resulted in a dose- and time-dependent induction of apoptosis, a process characterized by cell death, chromatin condensation, and DNA fragmentation. This apoptosis was linked to the release of cytochrome c from the mitochondria, activation of caspase-3, and cleavage of poly (ADP-ribose) polymerase (PARP), all of which are associated with apoptotic cell death. The study suggests that Humic Acid has potential anticancer properties and could be useful in the development of new drug products for cancer treatment.

Hsin-Ling Yang, You-Cheng Hseu, Yi-Ting Hseu, Fung-Jou Lu, Elong Lin, Jim-Shoung Lai. Humic acid induces apoptosis in human premyelocytic leukemia HL-60 cells. Life Sci. 2004 Aug 27;75(15):1817-31.

Shilajit as Fulvic & Humic Acid
The main components of Shilajit are fulvic and humic acid, so they are used essentially interchangeably for the name.
Shilajit, often referred to as "the conqueror of weakness," is a unique and ancient medicinal substance primarily found in the Himalayan region, including parts of India, China, Tibet, and Central Asia. This tar-like resin is formed over millions of years through the gradual decomposition of plant matter under immense pressure. It stands out for its remarkable composition of 85 different minerals and trace elements, many of which are increasingly rare in modern diets.
Historical Significance: Shilajit has been an integral part of Ayurvedic medicine for thousands of years and has earned a reputation for its potent health benefits. References to its use date back at least 2000 years in the Charaka Samhita, a Sanskrit text on Ayurveda. Legends suggest that even Aristotle and Alexander the Great recognized its therapeutic potential. An origin story recounts how people observed monkeys in the Himalayas consuming the sticky black substance and gaining remarkable strength and agility, leading humans to use it as well. Shilajit has a long history of being associated with increased vitality, strength, and resilience, often described as making individuals "as strong as a rock."
Composition: Shilajit's composition can vary depending on geographic factors, including mineral content in the rocks, plant varieties, altitude, and environmental conditions. It primarily consists of organic humic substances, which are composed of plant and microbial metabolites, including phytochemicals, fulvic acid, and naturally occurring colloidal minerals. Fulvic acid, in particular, plays a crucial role as a carrier for minerals, enhancing their bioavailability and cellular penetration. This substance also assists the body in absorbing and utilizing other nutrients effectively.
Key Health Benefits:
1. Adaptogenic Properties: Shilajit is considered an adaptogen, which means it helps the body adapt to stressors, promotes overall vitality, and enhances resistance to illness and fatigue.
2. Exercise Performance: Scientific studies haveshown that shilajit, when consumed, can lead to improvements in muscular strength, oxygen uptake, work capacity, and other exercise-related parameters. It appears to enhance physical performance.
3. Immune System Support: Shilajit can stimulate the production of Interleukin (IL-1), a protein vital for a healthy immune system. This property makes it particularly useful for individuals in high-altitude environments.
4. Cognitive Health: Research has explored shilajit's impact on memory and anxiety, suggesting cognitive-enhancing and anti-anxiety effects. It is believed to increase dopamine levels, contributing to improved mood.
5. Wound Healing: Shilajit has been traditionally used for wound healing. It promotes faster healing through accelerated wound contraction and increased hydroxyproline content.
6. Anti-Inflammatory: Shilajit has shown significant anti-inflammatory effects and can inhibit the formation of ulcers while enhancing protective mucous production in the stomach.
7. Pain Relief: Studies indicate that shilajit may haveanalgesic (pain-relieving) effects, potentially providing pain relief at lower doses compared to conventional medications.
8. Sexual Health: Shilajit has been referred to as a natural aphrodisiac and is knitric oxidewn for boosting libido and restoring hormonal balance. It has been studied for its potential to increase testosterone levels, sperm count, and motility.
9. Cancer Potential: Shilajit's humic compounds, humic acid (Humic Acid) and fulvic acid (Fulvic Acid), exhibit properties such as antioxidation, antimutagenesis, and potential antitumor effects. Shilajit is being explored as a complementary therapy for cancer patients.
10. Antimicrobial: Shilajit has antimicrobial properties and can inhibit the growth of various pathogenic microorganisms.
Shilajit is a fascinating and potent natural substance with a rich history and promising scientific support for various health benefits. However, it should be used with caution, ensuring quality and purity when incorporating it into your wellness regimen. As with any supplement, consult with a healthcare professional before starting shilajit, especially if you haveunderlying health conditions or are taking medications.
1. https://blog.biostarus.com/tag/quantum/
2. https://blog.biostarus.com/tag/quantum/
3. https://orexca.com/shilajit_uzbekistan.shtml
4. https://blog.biostarus.com/tag/quantum/
5. http://www.fulvic-acid-minerals.com/Fulvic/Chemistry%20of%20shilajit,.pdf
6. Bucci LR. Selected herbals and human exercise performance. Am J Clin Nutr. 2000 Aug; 72(2 Suppl):624S-36S
7. https://www.researchgate.net/profile/Ramesh_Gupta10/publication/279746105_Anti-Inflammatory_and_Anti-Arthritic_Efficacy_and_Safety_of_Purified_Shilajit_in_Moderately_Arthritic_Dogs.pdf
8. https://www.ncbi.nlm.nih.gov/pubmed/20532096
9. https://www.ncbi.nlm.nih.gov/pubmed/22771318
10. https://www.researchgate.net/publication/275715043_Effects_of_Shilajit_on_memory_anxiety_and_brain_monitric oxideamines_in_rats
11. https://www.hindawi.com/journals/ijad/2012/674142/
12. https://www.ncbi.nlm.nih.gov/pubmed/21785188
13. https://www.ncbi.nlm.nih.gov/pubmed/27006897
14. jbas.juw.edu.pk/index.php/JBAS/article/download/11/10/
15. https://www.ncbi.nlm.nih.gov/pubmed/2345464
16. https://www.ncbi.nlm.nih.gov/pubmed/25830280
17. https://www.ncbi.nlm.nih.gov/pubmed/20078516/
18. http://onlinelibrary.wiley.com/doi/10.1111/and.12482/full
19. Park JS, Kim GY, Han K. The spermatogenic and ovogenic effects of chronically administered Shilajit to rats. J Ethnitric oxidepHumic Acidrmacol. (2006)
20. http://altermed.com.ua/pdf/shilajit-a-panacea-for-cancer.pdf
21. https://www.naturalnews.com/055266_shilajit_heavy_metals_health_warning.html
Potential of shilajit to combat anemia from iron deficiency

In this study, the researchers aimed to investigate the potential anti-anemic effects of shilajit, a traditional medicinal substance, using rat models of iron deficiency anemia (IDA). Anemia is a condition characterized by a reduction in the number of red blood cells or a decrease in the amount of hemoglobin in the blood. Iron deficiency is the leading cause of anemia during pregnancy, particularly in developing countries.
Shilajit has a long history of use in traditional medicine and is believed to possess various health benefits, including its potential role in addressing anemia. The researchers conducted experiments to determine the appropriate dosage of shilajit and then assessed its impact on anemic rats through two different models:
1. Bleeding-Induced IDA Model: In this model, 18 rats were divided into three groups. The second and third groups of rats were made anemic by removing 2 ml of blood from each rat's retro-orbital plexus (a blood vessel) on five alternate days. The third group of anemic rats was treated with shilajit at a dose of 500 mg/kg/day from the 11th day after confirming anemia until the 20th day from the initial bleeding. Blood samples were collected on the 21st day to evaluate hematological parameters.
2. Low-Iron Diet-Induced IDA Model: Three groups of six rats each were used for this study. Group I was fed a normal rat diet, while Group II and III were given an iron-deficient diet for 13 days before the study. On the day of the study, the rats were fasted for one day, and Group III received shilajit treatment, starting on the 14th day after initiating the iron-deficient diet until the 20th day. Blood samples were collected at the end of the 20th day to assess hematological parameters.
Results:
• In the bleeding-induced IDA model, shilajit significantly increased the levels of hemoglobin (Hb), hematocrit (HCT), and red blood cells (RBC) compared to the untreated anemic control group.
• In the low-iron diet-induced IDA model, shilajit demonstrated a significant anti-anemic effect when administered at a dose of 500 mg/kg/day.
These findings suggest that shilajit may be effective in treating iron deficiency anemia, as it was able to increase hemoglobin levels and counteract anemia in the rat models. This indicates the potential of shilajit as a dietary supplement for managing iron deficiency anemia, particularly in cases where iron loss is common, such as during menstruation. However, further research is needed to confirm these effects in human subjects.
Velmurugan, Chinnasamy & Vivek, B. & Shekar, S.B. & Sudha, S.P. & Sundaram, T.. (2010). Shilajit in management of iron deficiency anaemia. J Pharm Biomed Sci. 1. 1-2.

Potential Anti-cancer effects of Fulvic and Humic acid
Fulvic acid is a natural substance found in humus, and its potential anti-cancer effects were investigated in this study. The research isolated Fulvic Acid from humus and examined its impact on immune-stimulating functions in RAW 264.7 cells. The study found that Fulvic Acid increased cell viability in a dose-dependent manner and promoted the production of nitric oxide (nitric oxide) in these cells. Fulvic Acid also upregulated the expression of inducible nitric oxide synthesis (iNOS) at both the protein and mRNA levels.
Furthermore, Fulvic Acid was observed to enhance the DNA-binding activity of nuclear factor-κB (NF-κB) in RAW 264.7 cells. When an NF-κB inhibitor was applied, it reduced Fulvic Acid-induced iNOS expression, suggesting that Fulvic Acid stimulates NF-κB, leading to increased iNOS and nitric oxide production.
The study also examined the effects of Fulvic Acid-stimulated culture media (Fulvic Acid-CM) from RAW 264.7 cells on MCA-102 fibrosarcoma cells. Fulvic Acid-CM was found to promote apoptosis (cell death) in MCA-102 fibrosarcoma cells. However, the inhibition of nitric oxide using an nitric oxide inhibitor called N(G)-monitric oxidemethyl-l-arginine (NMMA) only slightly reduced the apoptosis induced by Fulvic Acid-CM, and this reduction was associated with lower levels of nitric oxide.
In summary, this study suggests that Fulvic Acid likely stimulates immune-modulating molecules like nitric oxide and induces apoptosis in cancer cells, as demonstrated in MCA-102 fibrosarcoma cells and other human cancer cell lines like Hep3B, LNCaP, and HL60.
Rajapaksha Gedara Prasad Tharanga Jayasooriya, Matharage Gayani Dilshara, Chang-Hee Kang, Seungheon Lee, Yung Hyun Choi, Yong Kee Jeong, Gi-Young Kim. Fulvic acid promotes extracellular anti-cancer mediators from RAW 264.7 cells, causing to cancer cell death in vitro. Int Immunopharmacol. 2016 Jul ;36:241-8. Epub 2016 May 11.

In a study, researchers investigated the effects of Fulvic acid on immune-stimulating functions and cancer cell death. They found that Fulvic Acid enhanced the production of nitric oxide nitric oxide in immune cells (RAW 264.7 cells) and upregulated the expression of inducible nitric oxidde synthesis (initric oxideS) by activating NF-κB. When culture media from fulvic acid-stimulated immune cells were applied to cancer cells (MCA-102 fibrosarcoma cells), it induced apoptosis in the cancer cells. While nitric oxide played a role in this process, it was nitric oxidet the sole factor, suggesting that fulvic acid stimulates immune-modulating molecules like nitric oxide and promotes cancer cell apoptosis.

Rajapaksha Gedara Prasad Tharanga Jayasooriya, Matharage Gayani Dilshara, Chang-Hee Kang, Seungheon Lee, Yung Hyun Choi, Yong Kee Jeong, Gi-Young Kim. Fulvic acid promotes extracellular anti-cancer mediators from RAW 264.7 cells, causing to cancer cell death in vitro. Int Immunopharmacol. 2016 Jul ;36:241-8. Epub 2016 May 11.

Impact of Fulvic Acid on Certain Enzymes in Human Body
This study investigated the impact of Fulvic Acid (FA) on the expression of cyclooxygenase-2 (COX-2) in human monocytes when stimulated by homocysteine, a compound associated with vascular dysfunction and cardiovascular disease risks. Here is a more detailed summary:
Cardiovascular diseases are linked to inflammation and other risk factors, including elevated levels of homocysteine in the blood. The mechanism by which homocysteine contributes to vascular damage remains unclear, but it is known to affect endothelial function, cause oxidative stress, and promote inflammation. Monocytes, a type of white blood cell, are involved in the early stages of atherosclerotic plaque formation, and their activation and release of pro-inflammatory molecules are associated with atherosclerosis. COX-2 is an enzyme involved in the synthesis of pro-inflammatory molecules known as eicosanoids, and it plays a role in inflammation and atherosclerosis. This study aimed to understand how FA affects homocysteine-induced COX-2 expression in monocytes.
Methods:
1. Cell Culture: Human monocytes were isolated from peripheral blood, and the U937 cell line (a human monocytic cell line) was used for experiments. Cells were cultured under various conditions.
2. Gene Expression Analysis: Real-time PCR was used to measure COX-2 mRNA expression in response to different treatments.
3. PGE2 Assay: Enzyme-Linked Immunosorbent Assay (ELISA) was employed to quantify the secretion of prostaglandin E2 (PGE2), a pro-inflammatory molecule produced by COX-2.
4. Western Blot Analysis: Protein expression was analyzed using Western blotting to assess the activation of signaling pathways.
5. Luciferase Assays: Reporter gene assays were performed using COX-2 promoter constructs to investigate the transcriptional regulation of COX-2 by FA and homocysteine.
6. Transcription Factor Assays: Transcription factor ELISA assays were conducted to determine the activation of nuclear factor-κB (NF-κB), a key regulator of inflammatory gene expression.
7. Chromatin Immunoprecipitation (ChIP): ChIP assays were employed to study the binding of NF-κB to the COX-2 promoter region.
Results:
• FA did not have a cytotoxic effect on monocytes.
• Homocysteine induced COX-2 mRNA expression and PGE2 secretion in monocytes, and this effect was dose-dependently inhibited by pretreatment with FA.
• FA suppressed the homocysteine-induced activation of extracellular signal-regulated kinase (ERK) and c-Jun N-terminal kinase (JNK), two signaling pathways involved in inflammation.
• Homocysteine-induced COX-2 promoter activity was reduced by FA, indicating that FA acts at the transcriptional level.
• Pretreatment with FA inhibited homocysteine-induced NF-κB activation and its binding to the COX-2 promoter region in monocytes.
Conclusion: The study revealed that FA has an anti-inflammatory effect on monocytes stimulated with homocysteine by inhibiting COX-2 expression. This inhibition occurs at the transcriptional level and is mediated through the suppression of the ERK/JNK and NF-κB signaling pathways. These findings suggest that FA could be explored as a potential therapeutic agent for mitigating inflammation associated with cardiovascular diseases.
1. Motojima H, O Villareal M, Han J, Isoda H. Microarray analysis of immediate-type allergy in KU812 cells in response to fulvic acid. Cytotechnology. 2011;63:181–90. doi: 10.1007/s10616-010-9333-6. [PMC free article] [PubMed] [CrossRef] [Google Scholar]
2. Cornejo A, Jiménez JM, Caballero L, Melo F, Maccioni RB. Fulvic acid inhibits aggregation and promotes disassembly of tau fibrils associated with Alzheimer’s disease. J Alzheimers Dis. 2011;27:143–53. [PubMed] [Google Scholar]
3. Guzmán-Martinez L, Farías GA, Maccioni RB. Tau oligomers as potential targets for Alzheimer’s diagnosis and novel drugs. Front Neurol. 2013;4:167. doi: 10.3389/fneur.2013.00167. [PMC free article] [PubMed] [CrossRef] [Google Scholar]
4. Van Rensburg CEJ, Malfeld SCK, Dekker J. Topical application of oxifulvic acid suppresses the cutaneous immune response in mice. Drug Dev Res. 2001;53:29–32. doi: 10.1002/ddr.1166. [CrossRef] [Google Scholar]
5. Sherry L, Millhouse E, Lappin DF, Murray C, Culshaw S, Nile CJ, et al. Investigating the biological properties of carbohydrate derived fulvic acid (CHD-FA) as a potential novel therapy for the management of oral biofilm infections. BMC Oral Health. 2013;13:47. doi: 10.1186/1472-6831-13-47. [PMC free article] [PubMed] [CrossRef] [Google Scholar]
6. Yamada P, Isoda H, Han JK, Talorete TP, Abe Y. Inhibitory effect of fulvic acid extracted from Canadian sphagnum peat on chemical mediator release by RBL-2H3 and KU812 cells. Biosci Biotechnol Biochem. 2007;71:1294–305. doi: 10.1271/bbb.60702. [PubMed] [CrossRef] [Google Scholar]
7. Hansson GK, Hermansson A. The immune system in atherosclerosis. Nat Immunol. 2011;12:204–12. doi: 10.1038/ni.2001. [PubMed] [CrossRef] [Google Scholar]
8. Ghassibe-Sabbagh M, Platt DE, Youhanna S, Abchee AB, Stewart K, Badro DA, et al. Genetic and environmental influences on total plasma homocysteine and its role in coronary artery disease risk. Atherosclerosis. 2012;222:180–6. doi: 10.1016/j.atherosclerosis.2012.02.035. [PubMed] [CrossRef] [Google Scholar]
9. Lentz SR. Mechanisms of homocysteine-induced atherothrombosis. J Thromb Haemost. 2005;3:1646–54. doi: 10.1111/j.1538-7836.2005.01364.x. [PubMed] [CrossRef] [Google Scholar]
10. Kim CS, Kim YR, Naqvi A, Kumar S, Hoffman TA, Jung SB, et al. Homocysteine promotes human endothelial cell dysfunction via site-specific epigenetic regulation of p66shc. Cardiovasc Res. 2011;92:466–75. doi: 10.1093/cvr/cvr250. [PMC free article] [PubMed] [CrossRef] [Google Scholar]
11. Seneviratne AN, Sivagurunathan B, Monaco C. Toll-like receptors and macrophage activation in atherosclerosis. Clin Chim Acta. 2012;413:3–14. doi: 10.1016/j.cca.2011.08.021. [PubMed] [CrossRef] [Google Scholar]
12. Ricciotti E, FitzGerald GA. Prostaglandins and inflammation. Arterioscler Thromb Vasc Biol. 2011;31:986–1000. doi: 10.1161/ATVBAHA.110.207449. [PMC free article] [PubMed] [CrossRef] [Google Scholar]
13. Beloqui O, Páramo JA, Orbe J, Benito A, Colina I, Monasterio A, et al. Monocyte cyclooxygenase-2 overactivity: a new marker of subclinical atherosclerosis in asymptomatic subjects with cardiovascular risk factors? Eur Heart J. 2005;26:153–8. doi: 10.1093/eurheartj/ehi016. [PubMed] [CrossRef] [Google Scholar]
14. Yeh CC, Chang SF, Huang TY, Chang HI, Kuo HC, Wu YC, et al. Shear stress modulates macrophage-induced urokinase plasminogen activator expression in human chondrocytes. Arthritis Res Ther. 2013;15:R53. doi: 10.1186/ar4215. [PMC free article] [PubMed] [CrossRef] [Google Scholar]
15. Chang LC, Kuo HC, Chang SF, Chen HJ, Lee KF, Lin TH, et al. Regulation of ICAM-1 expression in gingival fibroblasts infected with high-glucose-treated P. gingivalis. Cell Microbiol. 2013;15:1722–34. [PubMed] [Google Scholar]
16. Chen TC, Tsai JP, Huang HJ, Teng CC, Chien SJ, Kuo HC, et al. Regulation of cyclooxygenase-2 expression in human bladder epithelial cells infected with type I fimbriated uropathogenic E. coli. Cell Microbiol. 2011;13:1703–13. doi: 10.1111/j.1462-5822.2011.01650.x. [PubMed] [CrossRef] [Google Scholar]
17. Chen TC, Chien SJ, Kuo HC, Huang WS, Sheen JM, Lin TH, et al. High glucose-treated macrophages augment E-selectin expression in endothelial cells. J Biol Chem. 2011;286:25564–73. doi: 10.1074/jbc.M111.230540. [PMC free article] [PubMed] [CrossRef] [Google Scholar]
18. Suematsu N, Ojaimi C, Kinugawa S, Wang Z, Xu X, Koller A, et al. Hyperhomocysteinemia alters cardiac substrate metabolism by impairing nitric oxide bioavailability through oxidative stress. Circulation. 2007;115:255–62. doi: 10.1161/CIRCULATIONAHA.106.652693. [PubMed] [CrossRef] [Google Scholar]
19. Zhang D, Fang P, Jiang X, Nelson J, Moore JK, Kruger WD, et al. Severe hyperhomocysteinemia promotes bone marrow-derived and resident inflammatory monocyte differentiation and atherosclerosis in LDLr/CBS-deficient mice. Circ Res. 2012;111:37–49. doi: 10.1161/CIRCRESAHA.112.269472. [PMC free article] [PubMed] [CrossRef] [Google Scholar]
20. Zhou J, Werstuck GH, Lhoták S, Shi YY, Tedesco V, Trigatti B, et al. Hyperhomocysteinemia induced by methionine supplementation does not independently cause atherosclerosis in C57BL/6 J mice. FASEB J. 2008;22:2569–78. doi: 10.1096/fj.07-105353. [PMC free article] [PubMed] [CrossRef] [Google Scholar]
21. Giannarelli C, Zafar MU, Badimon JJ. Prostanoid and TP-receptors in atherothrombosis: is there a role for their antagonism? Thromb Haemost. 2010;104:949–54. doi: 10.1160/TH10-03-0195. [PubMed] [CrossRef] [Google Scholar]
22. Motojima H, Yamada P, Han J, Ozaki M, Shigemori H, Isoda H. Properties of fulvic acid extracted from excess sludge and its inhibiting effect on β-hexosaminidase release. Biosci Biotechnol Biochem. 2009;73:2210–6. doi: 10.1271/bbb.90316. [PubMed] [CrossRef] [Google Scholar]
23. Iezzi A, Ferri C, Mezzetti A, Cipollone F. COX-2: friend or foe? Curr Pharm Des. 2007;13:1715–21. doi: 10.2174/138161207780831293. [PubMed] [CrossRef] [Google Scholar]
24. Zhao SP, Deng P, Huang HG, Xu ZM, Dai HY, Hong SC, et al. Expression of COX-2 mRNA in peripheral blood monocytes from patients with acute myocardial infarction and its significance. Clin Chem. 2005;51:2170–3. doi: 10.1373/clinchem.2005.054288. [PubMed] [CrossRef] [Google Scholar]
25. Cipollone F, Fazia M, Mezzetti A. Novel determinants of plaque instability. J Thromb Haemost. 2005;3:1962–75. doi: 10.1111/j.1538-7836.2005.01355.x. [PubMed] [CrossRef] [Google Scholar]
26. Lee YS, Lee SJ, Seo KW, Bae JU, Park SY, Kim CD. Homocysteine induces COX-2 expression in macrophages through ROS generated by NMDA receptor-calcium signaling pathways. Free Radic Res. 2013;47:422–31. doi: 10.3109/10715762.2013.784965. [PubMed] [CrossRef] [Google Scholar]
27. Vila-del Sol V, Fresno M. Involvement of TNF and NF-κB in the transcriptional control of cyclooxygenase-2 expression by IFN-γ in macrophages. J Immunol. 2005;174:2825–33. doi: 10.4049/jimmunol.174.5.2825. [PubMed] [CrossRef] [Google Scholar]
28. Ben-Neriah Y, Karin M. Inflammation meets cancer, with NF-κB as the matchmaker. Nat Immunol. 2011;12:715–23. doi: 10.1038/ni.2060. [PubMed] [CrossRef] [Google Scholar]
29. Wu N, Siow YL, O K. Induction of hepatic cyclooxygenase-2 by hyperhomocysteinemia via nuclear factor-κB activation. Am J Physiol Regul Integr Comp Physiol. 2009;297:R1086–94. doi: 10.1152/ajpregu.00293.2009. [PubMed] [CrossRef] [Google Scholar]