Blood Clot Prevention and Recovery Program
Research & Studies

Endothelial dysfunction in patients with spontaneous venous thromboembolism

 

“Patients with spontaneous venous thromboembolism have endothelial dysfunction, unlike age- and sex- matched controls. This finding suggests that spontaneous venous thromboembolism may be a condition associated with an enhanced risk of atherosclerosis.”

 

Migliacci, R., Becattini, C., Pesavento, R., Davi, G., Vedovati, M. C., Guglielmini, G., . . . Gresele, P. (2007). Endothelial dysfunction in patients with spontaneous venous thromboembolism. Haematologica, 92(6), 812-818. doi: 10.3324/haematol.10872

 

Molecular hydrogen protects mice against polymicrobial sepsis by ameliorating endothelial dysfunction via an Nrf2/HO-1 signaling pathway

 

“H2 regulated endothelial injury and the inflammatory response via Nrf2-mediated HO-1 levels. These results suggest that H2 could suppress excessive inflammatory responses and endothelial injury via an Nrf2/HO-1 pathway.”

 

Chen, H., Xie, K., Han, H., Li, Y., Liu, L., Yang, T., & Yu, Y. (2015). Molecular hydrogen protects mice against polymicrobial sepsis by ameliorating endothelial dysfunction via an Nrf2/HO-1 signaling pathway. International Immunopharmacology, 28(1), 643-654. doi: 10.1016/j.intimp.2015.07.034

 

Endothelial cell control of thrombosis

 

“In the face of endothelial dysfunction, endothelial cells trigger fibrin formation, as well as platelet adhesion and aggregation. Finally, endothelial cells release pro-fibrinolytic agents that initiate fibrinolysis to degrade the clot. Taken together, a functional endothelium is essential to maintain hemostasis and prevent thrombosis. Thus, a greater understanding into the role of the endothelium can provide new avenues for exploration and novel therapies for the management of thromboembolisms.”

 

Yau, J. W., Teoh, H., & Verma, S. (2015). Endothelial cell control of thrombosis. BioMed Central Cardiovascular Disorders, 15(130), 1-11. doi: 10.1186/s12872-015-0124-z

 

Consumption of water containing over 3.5 mg of dissolved hydrogen could improve vascular endothelial function

 

“Our data suggest that the daily consumption of water containing a high concentration of H2 (over 7 ppm or 3.5 mg in 500 mL of water) may aid in maintaining functional vasculature via two complementary mechanisms. One is neutralization of detrimental ROS to preserve NO bioavailability. The other mechanism is suppression of the inflammatory events that cause atherosclerosis.”

 

Ishibashi, T., Sakai, T., Sato, B., Hara, K., Hara, Y., Naritomi, Y., . . . Nagao, T. (2014). Consumption of water containing over 3.5 mg of dissolved hydrogen could improve vascular endothelial function. Vascular Health and Risk Management, 10(59), 1-7. doi: 10.2147/vhrm.s68844

 

Venous thromboembolism has the same risk factors as atherosclerosis: A PRISMA-compliant systemic review and meta-analysis

 

“Previous studies have shown that idiopathic pulmonary embolism is positively associated with other cardiovascular events, such as myocardial infarction and stroke, suggesting a potentially important association between atherosclerosis risk factors and venous thromboembolism (VTE). We performed a meta-analysis to evaluate the correlation between risk factors for atherosclerosis and VTE. Based on our systematic review and meta-analysis, we observed a significant association between VTE and the risk factors for atherosclerosis. These results may make an important contribution to clinical practice regarding VTE treatment.”

 

Mi, Y., Yan, S., Lu, Y., Liang, Y., & Li, C. (2016). Venous thromboembolism has the same risk factors as atherosclerosis: A PRISMA-compliant systemic review and meta-analysis. Medicine, 95(32), 1-13. doi: 10.1097/MD.0000000000004495

 

H2 inhibits TNF-α-induced lectin-like oxidized LDL receptor-1 expression by inhibiting nuclear factor κB activation in endothelial cells

 

“H(2) is a therapeutic antioxidant that can reduce oxidative stress. Oxidized low-density lipoprotein, which plays roles in atherosclerosis, may promote endothelial dysfunction by binding the cell-surface receptor LOX-1. H(2) inhibited the expression of LOX-1 and the activation of NF-κB in apolipoprotein E knockout mice, an animal model of atherosclerosis. Thus, H(2) probably inhibits cytokine-induced LOX-1 gene expression by suppressing NF-κB activation.”

 

Song, G., Tian, H., Liu, J., Zhang, H., Sun, X., & Qin, S. (2011). H2 inhibits TNF-α-induced lectin-like oxidized LDL receptor-1 expression by inhibiting nuclear factor κB activation in endothelial cells. Biotechnology Letters, 33(9), 1715-1722. doi: 10.1007/s10529-011-0630-8

 

Pathology of coronary atherosclerosis and thrombosis

 

“Thin-cap fibroatheroma (TCFA) is characterized by a relatively large necrotic core with an overlying thin fibrous cap measuring <65 µm typically containing numerous macrophages, and is considered to be the precursor lesion of plaque rupture which is the most common cause of coronary thrombosis. The second common cause of acute thrombosis is plaque erosion, while calcified nodules is known to be the least frequent cause of coronary thrombosis. Coronary thrombosis can occur without symptoms to form healed lesions, which contributes to an increase in plaque burden and luminal narrowing. The process of plaque progression is generally accompanied by the progression of calcification.”

 

Otsuka, F., Yasuda, S., Noguchi, T., & Ishibashi-Ueda, H. (2016). Pathology of coronary atherosclerosis and thrombosis. Cardiovascular Diagnosis and Therapy, 6(4), 396-408. doi: 10.21037/cdt.2016.06.01

 

Consumption of hydrogen water prevents atherosclerosis in apolipoprotein E knockout mice

 

“Atherosclerotic lesions were significantly reduced by ad libitum drinking of H2–water (p = 0.0069) as judged by Oil-Red-O staining series of sections of aorta. The oxidative stress level of aorta was decreased. Accumulation of macrophages in atherosclerotic lesions was confirmed. Thus, consumption of H2-dissolved water has the potential to prevent arteriosclerosis.”

 

Ohsawa, I., Nishimaki, K., Yamagata, K., Ishikawa, M., & Ohta, S. (2008). Consumption of hydrogen water prevents atherosclerosis in apolipoprotein E knockout mice. Biochemical and Biophysical Research Communications, 377(4), 1195-1198. doi: 10.1016/j.bbrc.2008.10.156 

 

Atherosclerosis, platelets and thrombosis in acute ischaemic heart disease

 

“Although an atherosclerotic plaque may remain clinically silent, it is prone to disruption, leading to local platelet activation, aggregation and the subsequent atherothrombotic episode.”

 

Badimon, L., Padro, T., & Vilahur, G. (2012). Atherosclerosis, platelets and thrombosis in acute ischaemic heart disease. European heart journal acute cardiovascular care, 1(1), 60-74. doi: 10.1177/2048872612441582

 

Hydrogen activates ATP-binding cassette transporter A1-dependent efflux ex vivo and improves high-density lipoprotein function in patients with hypercholesterolemia: A double-blinded, randomised and placebo-controlled trial

 

“H2 activates ATP-binding cassette transporter A1-dependent efflux, enhances HDL antiatherosclerotic functions, and has beneficial lipid-lowering effects. The present findings highlight the potential role of H2 in the regression of hypercholesterolemia and atherosclerosis.”

 

Song, G., Lin, Q., Zhao, H., Liu, M., Ye, F., Sun, Y., . . . Qin, S. (2015). Hydrogen activates ATP-binding cassette transporter A1-dependent efflux ex vivo and improves high-density lipoprotein function in patients with hypercholesterolemia: A double-blinded, randomized, and placebo-controlled trial. The Journal of Clinical Endocrinology & Metabolism, 100(7), 2724-2733. doi: 10.1210/jc.2015-1321

 

Tissue factor and atherothrombosis

 

“Atherosclerosis is a progressive disease characterized by the accumulation of lipids in medium to large sized arteries. Atherothrombosis is a term used to describe formation of a thrombus after rupture of an atherosclerotic plaque.”

 

Tatsumi, K., & Mackman, N. (2015). Tissue factor and atherothrombosis. Journal of Atherosclerosis and Thrombosis, 22(6), 543-549. doi: 10.5551/jat.30940

 

Molecular hydrogen stabilizes atherosclerotic plaque in low-density lipoprotein receptor-knockout mice

 

“Hydrogen (H(2)) attenuates the development of atherosclerosis in mouse models. The inhibitory effects of H(2) on the apoptosis of macrophage-derived foam cells, which take effect by suppressing the activation of the ERS pathway and by activating the Nrf2 antioxidant pathway, might lead to an improvement in atherosclerotic plaque stability.”

 

Song, G., Zong, C., Zhang, Z., Yu, Y., Yao, S., Jiao, P., . . . Qin, S. (2015). Molecular hydrogen stabilizes atherosclerotic plaque in low-density lipoprotein receptor-knockout mice. Free Radical Biology and Medicine, 87, 58-68. doi: 10.1016/j.freeradbiomed.2015.06.018

 

Expanding the clinical spectrum of OSA – An association with pulmonary embolism?

 

“Association between obstructive sleep apnea and pulmonary embolism are caused by similar pathogenic processes including increases in oxidative stress and vascular inflammation that promote endothelial dysfunction.”

Cistulli, P. A., & Phillips, C. L. (2010). Expanding the clinical spectrum of OSA – An association with pulmonary embolism? Sleep, 33(8), 1009–1010. Retrieved from https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2910530/

Molecular hydrogen alleviates cellular senescence in endothelial cells

 

“Substantial evidence indicates that molecular hydrogen (H2) has beneficial vascular effects because of its antioxidant and/or anti-inflammatory effects. H2 has long-lasting antioxidant and anti-aging effects on vascular endothelial cells through the Nrf2 pathway, even after transient exposure to H2. Hydrogen-rich water may thus be a functional drink that increases longevity.”

 

Hara, F., Tatebe, J., Watanabe, I., Yamazaki, J., Ikeda, T., & Morita, T. (2016). Molecular hydrogen alleviates cellular senescence in endothelial cells. Circulation Journal, 80(9), 2037-2046. doi: 10.1253/circj.cj-16-0227

 

The role of inflammation in venous thromboembolism and the link between arterial and venous thrombosis

 

“The key event in the initiation of venous thrombus formation is most probably vein wall inflammation. Inflammation is also supported by the relation of some risk factors to both arterial and venous thrombosis.”

Poredos, P., & Jezovnik, M. (2007). The role of inflammation in venous thromboembolism and the link between arterial and venous thrombosis. International Journal of Angiology, 26(4), 306-311.​ Retrieved from https://www.ncbi.nlm.nih.gov/pubmed/18091697

 

The evolution of molecular hydrogen: A noteworthy potential therapy with clinical significance

 

“Hydrogen is qualified to cross the blood brain barrier, to enter the mitochondria, and even has the ability to translocate to the nucleus under certain conditions. Once in these ideal locations of the cell, previous studies have shown that hydrogen exerts antioxidant, anti-apoptotic, anti-inflammatory, and cytoprotective properties that are beneficial to the cell. Hydrogen therapy [also] reduces hydroxyl radical and increases endogenous antioxidants caused by oxidative stress. Molecular hydrogen is proposed to be protective by increasing endogenous antioxidants in addition to scavenging the hydroxyl radical after an injury such as oxidative stress.”

 

Dixon, B. J., Tang, J., & Zhang, J. H. (2013). The evolution of molecular hydrogen: A noteworthy potential therapy with clinical significance.  ​Medical Gas Research, 3(10), 1-12. doi: 10.1186/2045-9912-3-10

Diabetes increases the risk of deep-vein thrombosis and pulmonary embolism. A population-based cohort study

 

“The T2DM patients had a substantially higher risk of DVT (aHR = 5.10, 95% CI = 3.12-8.32) and PE (aHR = 7.50, 95% CI = 3.29-17.1) development than the controls did in adults aged 49 years and younger. In conclusion, the longitudinal nationwide cohort study indicated that T2DM patients carried greater risks of developing VTE than did the general population.”

 

Chung, W., Lin, C., & Kao, C. (2015). Diabetes increases the risk of deep-vein thrombosis and pulmonary embolism. Thrombosis and Haemostasis, 114(4), 812-818. doi: 10.1160/th14-10-0868

 

Therapeutic effects of hydrogen saturated saline on rat diabetic model and insulin resistant model via reduction of oxidative stress

 

“Hydrogen saturated saline showed great efficiency in improving the insulin sensitivity and lowering blood glucose and lipids. Hydrogen saturated saline markedly attenuated the malondialdehyde level and elevated the levels of antioxidants superoxide dismutase and glutathione.”

 

Wang, Q., Zha, X., Kang, Z., Xu, M., Huang, Q., & Zou, D. (2012). Therapeutic effects of hydrogen saturated saline on rat diabetic model and insulin resistant model via reduction of oxidative stress. Chinese Medical Journal, 125(9), 1633-1637. Retrieved from https://www.ncbi.nlm.nih.gov/pubmed/22800834

 

Venous thromboembolism in patients with diabetes mellitus

 

“Patients with diabetes who developed venous thromboembolism were more likely to suffer a complicated clinical course. Diabetes was an independent predictor of recurrent deep vein thrombosis. We observed a low rate of thromboprophylaxis in diabetic patients. Further studies should focus on venous thromboembolism prevention in this vulnerable population.”

 

Piazza, G., Goldhaber, S. Z., Kroll, A., Goldberg, R. J., Emery, C., & Spencer, F. A. (2012). Venous thromboembolism in patients with diabetes mellitus. The American Journal of Medicine, 125(7), 709-716. doi: 10.1016/j.amjmed.2011.12.004

 

Supplementation of hydrogen-rich water improves lipid and glucose metabolism in patients with type 2 diabetes or impaired glucose tolerance

 

“In 4 of 6 patients with impaired glucose tolerance, intake of hydrogen-rich water normalized the oral glucose tolerance test. In conclusion, these results suggest that supplementation with hydrogen-rich water may have a beneficial role in prevention of T2DM and insulin resistance.”

 

Kajiyama, S., Hasegawa, G., Asano, M., Hosoda, H., Fukui, M., Nakamura, N., . . . Yoshikawa, T. (2008). Supplementation of hydrogen-rich water improves lipid and glucose metabolism in patients with type 2 diabetes or impaired glucose tolerance. Nutrition Research, 28(3), 137-143. doi: 10.1016/j.nutres.2008.01.008 

 

 

Inflammation and thrombosis

 

“Systemic inflammation is a potent prothrombotic stimulus.”

Esmon, C. (2003). Inflammation and thrombosis. Journal of Thrombosis and Haemostasis, 1(7), 1343-1348. doi: 10.1046/j.1538-7836.2003.00261.x

 

Hydrogen as a selective antioxidant: A review of clinical and experimental studies

“H2 is emerging as a novel and safe therapeutic antioxidant. It has selective antioxidant properties, giving it anti-inflammatory properties.”

 

Hong, Y., Chen, S., & Zhang, J. (2010). Hydrogen as a selective antioxidant: A review of clinical and experimental studies. Journal of International Medical Research, 38(6), 1893-1903. doi: 10.1177/147323001003800602 

 

​Intravenous release of NO from lipidic microbubbles accelerates deep vein thrombosis resolution in a rat model

 

“The antithrombotic properties of NO microbubbles may be associated with reduced platelets and inflammatory cells aggregation, enhanced collagen turnover and stimulus to an anticoagulant condition of endothelium.”

 

Wang, C., Yang, F., Xu, Z., Shi, D., Chen, D., Dai, J., . . . Jiang, Q. (2013). Intravenous release of NO from lipidic microbubbles accelerates deep vein thrombosis resolution in a rat model. Thrombosis Research, 131(1), 31-38. doi: 10.1016/j.thromres.2012.11.002

 

Chronic hydrogen-rich saline treatment attenuates vascular dysfunction in spontaneous hypertensive rats

 

“Treatment with HRS alleviates vascular dysfunction through abating oxidative stress, restoring baroreflex function, suppressing inflammation, preserving mitochondrial function, and enhancing nitric oxide bioavailability.”

 

Zheng, H., & Yu, Y. (2012). Chronic hydrogen-rich saline treatment attenuates vascular dysfunction in spontaneous hypertensive rats. Biochemical Pharmacology, 83(9), 1269-1277. doi: 10.1016/j.bcp.2012.01.031

Hydrogen acts as a therapeutic antioxidant by selectively reducing cytotoxic oxygen radicals

“Hydrogen selectively reduces the hydroxyl radical, the most toxic free radical, and effectively protects cells. It does not react with free radicals that have physiological benefits, making it an incredibly effective therapy to neutralize acute oxidative stress.”

Ohsawa, I., Ishikawa, M., Takahashi, K., Watanabe, M., Nishimaki, K., Yamagata, K., . . . Ohta, S. (2007). Hydrogen acts as a therapeutic antioxidant by selectively reducing cytotoxic oxygen radicals. Nature Medicine, 13(6), 688-694. doi: 10.1038/nm1577

 

​Molecular hydrogen as an emerging therapeutic medical gas for neurodegenerative and other diseases

 

“Molecular hydrogen has been observed to have beneficial effects for a variety of disease models, including myocardial infarcation and atherosclerosis.”

 

Ohno, K., Ito, M., Ichihara, M., & Ito, M. (2012). Molecular hydrogen as an emerging therapeutic medical gas for neurodegenerative and other diseases. Oxidative Medicine and Cellular Longevity, 2012(353152), 1-11. doi: 10.1155/2012/353152

 

Recent progress toward hydrogen medicine: Potential of molecular hydrogen for preventive and therapeutic applications

“H2 has a number of advantages as a potential antioxidant: H2 rapidly diffuses into tissues and cells, and it is mild enough neither to disturb metabolic redox reactions nor to affect reactive oxygen species (ROS) that function in cell signaling, thereby, there should be little adverse effects of consuming H2. H2 shows not only effects against oxidative stress, but also various anti-inflammatory and anti-allergic effects. H2 regulates various gene expressions and protein-phosphorylations as well.”

 

Ohta, S. (2011). Recent progress toward hydrogen medicine: Potential of molecular hydrogen for preventive and therapeutic applications. Current Pharmaceutical Design, 17(22), 2241-2252. doi: 10.2174/138161211797052664 

 

Oxidative stress and thrombotic disorders: Study in patients with venous thromboembolism

 

“Oxidative stress may be one of the causative factors in venous thromboembolism and probably contributes to additional disorders.”

Reguig, S. B., Bouanane, S., Merzouk, H., Soufi, N. & Merzouk, S. A. (2016) Oxidative stress and thrombotic disorders: Study in patients with venous thromboembolism. International Journal of Health Sciences and Research), 6(1), 185-194. Retrieved from http://www.scopemed.org/?mno=214288#cite

 

​A review of hydrogen as a new medical therapy

 

“In the past few years many initial and subsequent clinical studies have demonstrated that hydrogen can act as an important physiological regulatory factor to cells and organs on the antioxidant, anti-inflammatory, anti-apoptotic and other protective effects. So far several delivery methods applied in these studies have proved to be available and convenient, including inhalation, drinking hydrogen-dissolved water and injection with hydrogen-saturated saline.”

 

Zhang, J., Liu, C., Zhou, L., Qu, K., Wang, R., Tai, M., . . . Wang, Z. (2012). A Review of hydrogen as a new medical therapy. Hepatogastroenterology, 59(116), 1026-1032. doi: 10.5754/hge11883

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​Hydrogen-rich water decreases serum LDL-cholesterol levels and improves HDL function in patients with potential metabolic syndrome

 

“Supplementation with H2-rich water seems to decrease serum LDL-C and apoB levels, improve dyslipidemia-injured HDL functions, and reduce oxidative stress, and it may have a beneficial role in prevention of potential metabolic syndrome.”

 

Song, G., Li, M., Sang, H., Zhang, L., Li, X., Yao, S., . . . Qin, S. (2013). Hydrogen-rich water decreases serum LDL-cholesterol levels and improves HDL function in patients with potential metabolic syndrome. Journal of Lipid Research, 54(7), 1884-1893. doi: 10.1194/jlr.M036640

 

​The role of inflammation in early and late venous thrombosis: Are there clinical implications?

 

“Venous thrombosis is associated with a significant inflammatory response. Inflammatory cells, adhesion molecules (especially selectins), cytokines, and procoagulant microparticles appear to be associated with the thrombogenic process.”

 

Wakefield, T. W., & Henke, P. K. (2005). The role of inflammation in early and late venous thrombosis: Are there clinical implications? Seminars in Vascular Surgery, 18(3), 118-129. doi: 10.1053/j.semvascsurg.2005.05.003

​Molecular hydrogen as a preventive and therapeutic medical gas: Initiation, development and potential of hydrogen medicine

 

“The numerous publications on its biological and medical benefits revealed that H2 reduces oxidative stress not only by direct reactions with strong oxidants, but also indirectly by regulating various gene expressions. Moreover, by regulating the gene expressions, H2 functions as an anti-inflammatory and anti-apoptotic, and stimulates energy metabolism.”

 

Ohta, S. (2014). Molecular hydrogen as a preventive and therapeutic medical gas: Initiation, development and potential of hydrogen medicine. Pharmacology & Therapeutics, 144(1), 1-11. doi: 10.1016/j.pharmthera.2014.04.006

 

Cancer-associated thrombosis: Prevention and treatment

 

“It is well established that cancer patients are at an increased risk of venous thromboembolism (vte). In fact, the presence of malignancy increases the risk of vte by a factor of 4 to 6, and large population-based studies show that the incidence of vte is on the rise. Overall, cancer patients constitute 15%–20% of the patients diagnosed with vte, and depending on the type of tumour, extent of malignancy, type of cancer treatment, and presence of other risk factors, 1%–25% of patients with malignancy will develop thrombosis.”

 

Brose, K., & Lee, A. (2008). Cancer-associated thrombosis: Prevention and treatment. Current Oncology, 15(S1), 58-67. doi: 10.3747/co.2008.177

 

Hydrogen-water enhances 5-fluorouracil-induced inhibition of colon cancer

 

“Oxidative stress is involved in cancer development. Hydrogen (H2) is a potent antioxidant and exhibits anti-inflammatory and potentially anticancer-like activities. High-content hydrogen water can inhibit colon cancer, particularly in combination with 5-fluorouracil.”

 

Runtuwene, J., Amitani, H., Amitani, M., Asakawa, A., Cheng, K., & Inui, A. (2015). Hydrogen–water enhances 5-fluorouracil-induced inhibition of colon cancer. PeerJ, 3, 1-15. doi: 10.7717/peerj.859 

 

Thrombosis in cancer: Research priorities identified by a national cancer institute/national heart, lung, and blood institute strategic working group

 

“The risk for venous thromboembolism (VTE) is increased in cancer and particularly with chemotherapy, and it portends poorer survival among patients with cancer.”

 

Key, N. S., Khorana, A. A., Mackman, N., Mccarty, O. J., White, G. C., Francis, C. W., . . . Sood, A. K. (2016). Thrombosis in cancer: Research priorities identified by a national cancer institute/national heart, lung, and blood institute strategic working group. Cancer Research, 76(13), 3671-3675. doi: 10.1158/0008-5472.can-15-3100

 

Hydrogen-rich saline attenuate chemotherapy-induced ovarian injury via regulation of oxidative stress

 

“Hydrogen has been reported to exert a therapeutic effect in several diseases due to its antioxidative, anti-inflammatory and anti-apoptotic properties. Hydrogen‑rich saline exerts a protective effect against cisplatin-induced ovarian injury by reducing MDA and increasing SOD and CAT activity. Ovarian injury induced by chemotherapy involves the activation of Nrf2.”

 

Meng, X., Chen, H., Wang, G., Yu, Y., & Xie, K. (2015). Hydrogen-rich saline attenuates chemotherapy-induced ovarian injury via regulation of oxidative stress. Experimental and Therapeutic Medicine, 10(6), 2277-2282. doi: 10.3892/etm.2015.2787

 

The effects of obesity on venous thromboembolism: A review

 

“Although the association between obesity and VTE appears to be moderate, obesity can interact with other environmental or genetic factors and pose a significantly greater risk of VTE among individuals who are obese and who are exposed simultaneously to several other risk factors for VTE.”

 

Yang, G., Staercke, C. D., & Hooper, W. C. (2012). The effects of obesity on venous thromboembolism: A review. Open Journal of Preventive Medicine, 2(4), 499-509. doi: 10.4236/ojpm.2012.24069

 

Molecular hydrogen improves obesity and diabetes by inducing hepatic FGF21 and stimulating energy metabolism in db/db mice

 

“Long-term drinking H(2)-water significantly controlled fat and body weights, despite no increase in consumption of diet and water. The present results suggest the potential benefit of H(2) in improving obesity, diabetes, and metabolic syndrome.”

 

Kamimura, N., Nishimaki, K., Ohsawa, I., & Ohta, S. (2011). Molecular hydrogen improves obesity and diabetes by inducing hepatic FGF21 and stimulating energy metabolism in db/db mice. Obesity, 19(7), 1396-1403. doi: 10.1038/oby.2011.6

 

Mechanisms of thrombosis in obesity

 

“Obesity-driven chronic inflammation and impaired fibrinolysis appear to be major effector mechanisms of thrombosis in obesity. The proinflammatory and hypofibrinolytic effects of obesity may be exacerbated by dysregulated expression and secretion of adipokines and microRNAs, which further increase the risk of thrombosis and suggest new potential targets for therapy.”

 

Blokhin, I. O., & Lentz, S. R. (2013). Mechanisms of thrombosis in obesity. Current Opinion in Hematology, 20(5), 437-444. doi: 10.1097/moh.0b013e3283634443

 

Molecular hydrogen attenuates fatty acid uptake and lipid accumulation through downregulating CD36 expression in HepG2 cells

 

“Pretreatment with hydrogen reduced fatty acid uptake and lipid accumulation after palmitate overload in HepG2 cells, which was associated with inhibition of JNK activation. Hydrogen treatment did not alter CD36 mRNA expression but reduced CD36 protein expression.

 

Iio, A., Ito, M., Itoh, T., Terazawa, R., Fujita, Y., Nozawa, Y., . . . Ito, M. (2013). Molecular hydrogen attenuates fatty acid uptake and lipid accumulation through downregulating CD36 expression in HepG2 cells. Medical Gas Research, 3(6), 1-7. doi: 10.1186/2045-9912-3-6

 

Congestive heart failure and Virchow's triad: A neglected association

 

“Congestive heart failure (CHF) is associated with significant morbidity and mortality. In particular, patients with CHF have a high risk of venous thromboembolism and stroke, as well as recurrent ischaemia and infarction.”

 

Sosin, M. D., Bhatia, G., Davis, R. C., & Lip, G. Y. (2003). Congestive heart failure and Virchow’s Triad: A Neglected Association. Wiener Medizinische Wochenschrift, 153(19-20), 411-416. doi: 10.1007/s10354-003-0027-y

 

Anti-inflammatory effect of hydrogen-rich saline in a rat model of regional myocardial ischemia and reperfusion

 

“Attenuated the increase of I/R induced proinflammatory cytokine tumor necrosis factor-α (TNF-a) and interleukin-1β (IL-1b) levels in the AAR. H(2) saline has an anti-inflammatory effect on rat hearts with regional myocardial I/R.”

 

Zhang, Y., Sun, Q., He, B., Xiao, J., Wang, Z., & Sun, X. (2011). Anti-inflammatory effect of hydrogen-rich saline in a rat model of regional myocardial ischemia and reperfusion. International Journal of Cardiology, 148(1), 91-95. doi: 10.1016/j.ijcard.2010.08.058

 

Heart failure in patients with deep vein thrombosis

 

“Patients with heart failure (HF) are particularly vulnerable to the development of venous thromboembolism (VTE) and its related complications of pulmonary embolism and right ventricular failure.”

 

Piazza, G., Seddighzadeh, A., & Goldhaber, S. Z. (2008). Heart Failure in Patients With Deep Vein Thrombosis. The American Journal of Cardiology, 101(7), 1056-1059. doi: 10.1016/j.amjcard.2007.11.051

 

Hydrogen-containing saline attenuates doxorubicin-induced heart failure in rats

 

“Cardiac function was significantly improved and that the plasma levels of oxidative-stress markers and myocardial autophagic activity were decreased in animals treated with hydrogen-containing saline. Therefore, we conclude that hydrogen-containing saline may have beneficial effects for doxorubicin-induced heart failure.”

Wu, S., Zhu, L., Yang, J., Fan, Z., Dong, Y., Luan, R., . .  . Fu, L. (2014). Hydrogen-containing saline attenuates doxorubicin-induced heart failure in rats. Pharmazie, 69(8), 633-636. doi: 10.1691/ph.2014.3859

 

Venous thromboembolism in patients with inflammatory bowel disease: Focus on prevention and treatment

 

“IBD patients have a risk of VTE that is 2- to 3-fold greater than that of the general population. This risk is higher during disease flares, both for inpatients and outpatients.”

 

Papa, A., Gerardi, V., Marzo, M., Felice, C., Rapaccini, G. L., & Gasberrini, A. (2014). Venous thromboembolism in patients with inflammatory bowel disease: Focus on prevention and treatment. World Journal of Gastroenterology, 20(12), 3173-3179. doi: 10.3748/wjg.v20.i12.3173

 

Protective effects of hydrogen-rich saline on ulcerative colitis rat model

 

“Treatment with hydrogen-rich saline reduced the weight loss and diarrhea and alleviated the colonic mucosal damage in the UC rats. In addition, the expression of vascular endothelial growth factor in the UC rats increased and could be inhibited by hydrogen treatment. Antioxidative hydrogen-rich saline effectively protected the rats from UC, which might be, at least in part, because of inhibition of vascular endothelial growth factor.”

 

He, J., Xiong, S., Zhang, J., Wang, J., Sun, A., Mei, X., . . . Wang, Q. (2013). Protective effects of hydrogen-rich saline on ulcerative colitis rat model. Journal of Surgical Research, 185(1), 174-181. doi: 10.1016/j.jss.2013.05.047

 

Inflammatory bowel disease and thromboembolism

 

“Patients with inflammatory bowel disease (IBD) have an increased risk of vascular complications. Thromboembolic complications, both venous and arterial, are serious extraintestinal manifestations complicating the course of IBD and can lead to significant morbidity and mortality.”

 

Zezos, P. (2014). Inflammatory bowel disease and thromboembolism. World Journal of Gastroenterology, 20(38), 13863-13878. doi: 10.3748/wjg.v20.i38.13863

 

Hydrogen mediates suppression of colon inflammation induced by dextran sodium sulfate

 

“By its antioxidant effect, molecular hydrogen gas (H2) was reported to protect organs from tissue damage induced by ischemia reperfusion. Histological analysis also revealed that the DSS-mediated colonic tissue destruction accompanied by macrophage infiltration was remarkably suppressed by H2. Therefore, the present study indicated that H2 can prevent the development of DSS-induced colitis in mice.”

 

Kajiya, M., Silva, M. J., Sato, K., Ouhara, K., & Kawai, T. (2009). Hydrogen mediates suppression of colon inflammation induced by dextran sodium sulfate. Biochemical and Biophysical Research Communications, 386(1), 11-15. doi: 10.1016/j.bbrc.2009.05.117

 

Rheumatoid arthritis increases the risk of deep vein thrombosis and pulmonary thromboembolism: A nationwide cohort study

 

“From 23.74 million people in the cohort, 29 238 RA patients (77% women, mean age of 52.4 years) and 1 16 952 controls were followed 1 93 753 and 7 92 941 person-years, respectively. The risk of developing DVT and PE was 3.36-fold and 2.07-fold, respectively, in patients with RA compared with patients without RA, after adjusting for age, sex and comorbidities. The multiplicative increased risks of DVT and PE were also significant in patients with RA with any comorbidity. This nationwide prospective cohort study demonstrates that DVT and PE risks significantly increased in patients with RA compared with those of the general population.”

 

Chung, W., Peng, C., Lin, C., Chang, Y., Chen, Y., Chiang, J. Y., . . . Kao, C. (2013). Rheumatoid arthritis increases the risk of deep vein thrombosis and pulmonary thromboembolism: A nationwide cohort study. Annals of the Rheumatic Diseases, 73(10), 1774-1780. doi: 10.1136/annrheumdis-2013-203380

 

Consumption of water containing a high concentration of molecular hydrogen reduces oxidative stress and disease activity in patients with rheumatoid arthritis: An open-label pilot study

 

“Rheumatoid arthritis (RA) is a chronic inflammatory disease characterized by the destruction of bone and cartilage. Although its etiology is unknown, the hydroxyl radical has been suggested to be involved in the pathogenesis of RA. The results suggest that the hydroxyl radical scavenger H2 effectively reduces oxidative stress in patients with this condition. The symptoms of RA were significantly improved with high H2 water.”

 

Ishibashi, T., Sato, B., Rikitake, M., Seo, T., Kurokawa, R., Hara, Y., . . . Nagao, T. (2012). Consumption of water containing a high concentration of molecular hydrogen reduces oxidative stress and disease activity in patients with rheumatoid arthritis: An open-label pilot study. Medical Gas Research, 2(27), 1-8. doi: 10.1186/2045-9912-2-27

 

Risk of venous thromboembolism in patients with rheumatoid arthritis

 

“Our results showed an increased risk of developing VTE for RA patients compared with non-RA patients. The risk was attenuated but remained elevated even after adjusting for various risk factors for VTE.”

 

Kim, S. C., Schneeweiss, S., Liu, J., & Solomon, D. H. (2013). Risk of venous thromboembolism in patients with rheumatoid arthritis. Arthritis Care & Research, 65(10), 1600-1607. doi: 10.1002/acr.22039

 

Therapeutic efficacy of infused molecular hydrogen in saline on rheumatoid arthritis: A randomized, double-blind, placebo-controlled pilot study

 

“The aim of this study was to demonstrate the safety and efficacy of H2-saline infusion for treatment of rheumatoid arthritis (RA). We conducted a randomized, double-blind, placebo-controlled investigation of the infusion of 1 ppm H2-dissolved saline (H2-saline) in 24 RA patients. Drop infusion of H2 safely and effectively reduced RA disease activity.”

 

Ishibashi, T., Sato, B., Shibata, S., Sakai, T., Hara, Y., Naritomi, Y., . . . Nagao, T. (2014). Therapeutic efficacy of infused molecular hydrogen in saline on rheumatoid arthritis: A randomized, double-blind, placebo-controlled pilot study. International Immunopharmacology, 21(2), 468-473. doi: 10.1016/j.intimp.2014.06.001

 

Thrombosis associated with viral hepatitis

 

“Viral hepatitis may promote the development of venous thromboembolism (VTE) and, more specifically, portal vein thrombosis (PVT).”

 

Galli, L., Victor E A. Gerdes, L. Guasti, and A. Squizzato. (2014). Thrombosis associated with viral hepatitis. Journal of Clinical and Translational Hepatology, 2(4): 234-39. doi: 10.14218/jcth.2014.00031

 

Hydrogen-rich water prevents progression of nonalcoholic steatohepatitis and accompanying hepatocarcinogenesis in mice

 

“Oxidative stress is a strong contributor to the progression from simple fatty liver to nonalcoholic steatohepatitis (NASH). Consumption of hydrogen-rich water may be an effective treatment for NASH by reducing hepatic oxidative stress, apoptosis, inflammation, and hepatocarcinogenesis.”

 

Kawai, D., Takaki, A., Nakatsuka, A., Wada, J., Tamaki, N., Yasunaka, T., . . . Yamamoto, K. (2012). Hydrogen-rich water prevents progression of nonalcoholic steatohepatitis and accompanying hepatocarcinogenesis in mice. Hepatology, 56(3), 912-921. doi: 10.1002/hep.25782

 

Viral hepatitis and thrombosis: A narrative review

 

“Recent studies suggest a possible role of viral hepatitis in the development of VTE and, in particular, of portal vein thrombosis.”

 

Squizzato, A., & Gerdes, V. (2012). Viral hepatitis and thrombosis: A narrative review. Seminars in Thrombosis and Hemostasis, 38(5), 530-534. doi: 10.1055/s-0032-1305783

 

Effect of hydrogen-rich water on oxidative stress, liver function, and viral load in patients with chronic hepatitis B

 

“When compared with controls, oxidative stress was obvious in CHB patients, and the liver function also significantly impaired. After treatment, the oxidative stress remained unchanged in routine treatment group, but markedly improved in hydrogen treatment group. HRW significantly attenuates oxidative stress in CHB patients, but further study with long-term treatment is required to confirm the effect of HRW on liver function and HBV DNA level.”
 

Xia, C., Liu, W., Zeng, D., Zhu, L., Sun, X., & Sun, X. (2013). Effect of hydrogen-rich water on oxidative stress, liver function, and viral load in patients with chronic hepatitis B. Clinical and Translational Science, 6(5), 372-375. doi: 10.1111/cts.12076

 

Cigarette smoking and the risk of venous thromboembolism: The Tromsø study

 

“Heavy smoking was apparently a risk factor for provoked VTE in analyses with VTE events as the only outcome. The lack of association between smoking and risk of VTE in analyses censored at the occurrence of cancer or myocardial infarction may suggest that smoking-attributable diseases or other predisposing factors are essential for smoking to convey a risk of VTE.”

 

Enga, K. F., Braekkan, S. K., Hansen-Krone, I. J., Cessie, S. L., Rosendaal, F. R., & Hansen, J. (2012). Cigarette smoking and the risk of venous thromboembolism: The Tromsø study. Journal of Thrombosis and Haemostasis, 10(10), 2068-2074. doi: 10.1111/j.1538-7836.2012.04880.x

 

Attenuation of cigarette smoke-induced airway mucus production by hydrogen-rich saline in rats

 

“Hydrogen-rich saline pretreatment ameliorated CS-induced airway mucus production and airway epithelium damage in rats. The protective role of hydrogen on CS-exposed rat lungs was achieved at least partly by its free radical scavenging ability. This is the first report to demonstrate that intraperitoneal administration of hydrogen-rich saline protected rat airways against CS damage and it could be promising in treating abnormal airway mucus production in COPD.”

 

Ning, Y., Shang, Y., Huang, H., Zhang, J., Dong, Y., Xu, W., & Li, Q. (2013). Attenuation of cigarette smoke-Induced airway mucus production by hydrogen-rich saline in rats. PLOS ONE, 8(12), 1-10. doi: 10.1371/journal.pone.0083429

 

Venous thromboembolism in patients with chronic obstructive pulmonary disease

 

“We observed that patients with chronic obstructive pulmonary disease who subsequently developed venous thromboembolism had a 70% higher rate of in-hospital death and twice the rate of dying within 30 days of venous thromboembolism diagnosis compared with venous thromboembolism patients who did not have chronic obstructive pulmonary disease.”

 

Piazza, G., Goldhaber, S. Z., Kroll, A., Goldberg, R. J., Emery, C., & Spencer, F. A. (2012). Venous thromboembolism in patients with chronic obstructive pulmonary disease. American Journal of Medicine, 125(10), 1010-1018. doi: 10.1016/j.amjmed.2012.03.007

 

Hydrogen therapy may be a novel and effective treatment for COPD

 

“Studies have shown that ROS played a pivotal role in the development of COPD and some antioxidants were effective in the protection against the damaging effects of oxidative stress. Therefore, we hypothesize that owing to its peculiarity to eliminate toxic ROS, hydrogen therapy may be a novel and effective treatment for COPD.”

 

Liu, S., Liu, K., Sun, Q., Liu, W., Tao, H., & Sun, X. (2011). Hydrogen therapy may be a novel and effective treatment for COPD. Frontiers in Pharmacology, 2(19), 1-2. doi: 10.3389/fphar.2011.00019

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