Hydrogen water intake during chemotherapy in colon cancer patients.

Hydrogen water intake during chemotherapy in colon cancer patients.
4 March 2024

The H2MEDICAL team presents you a medical report translated from English after a study of colon cancer patients who took hydrogen water during a series of chemotherapy treatments. The paper is titled "Protective effect of hydrogen water on liver function of colorectal cancer patients treated with mFOLFOX6 chemotherapy." and is published in PubMed /see the report here/.

 

Abstract

The present study was conducted to investigate the protective effect of hydrogen-rich water on liver function of colorectal cancer (CRC) patients treated with mFOLFOX6 chemotherapy. A controlled, randomized, single-blind clinical trial was designed. A total of 152 CRC patients were recruited from the oncology department of Taishan Hospital (Taian, China) between June 2010 and February 2016, among whom 146 met the inclusion criteria. Subsequently, 144 patients were randomized into the treatment (n = 80) and placebo (n = 64) groups. At the end of the study, 76 patients in the hydrogen treatment group and 60 patients in the placebo group were included in the final analysis. Changes in liver function after chemotherapy were observed, such as altered levels of alanine aminotransferase (ALT), aspartate transaminase (AST), alkaline phosphatase, indirect bilirubin (IBIL), and direct bilirubin.The deleterious effects of mFOLFOX6 chemotherapy on liver function are mainly represented by elevated ALT, AST and IBIL levels. The group receiving hydrogen-rich water (hydrogen water) showed no significant differences in liver function before and after chemotherapy, whereas the placebo group showed significantly increased ALT, AST, and IBIL levels. This indicates that hydrogen water reduces mFOLFOX6-related liver injury.

 

Introduction


Antitumor agents are primarily cytotoxic drugs that inevitably cause damage to normal tissue cells and organs or induce an adverse reaction in killing cancer cells. Chemotherapeutic agents can cause liver damage, including necrosis or fatty degeneration of liver cells, cholestasis, and damage to hepatic vessels (1-4). Liver dysfunction tends to affect the course of antitumor treatment, increasing patient discomfort and overall financial burden.

Hydrogen is a natural gas with no color, taste, or odor, and its protective effect against oxidative damage to the brain, liver, kidneys, and other major organs has been described previously (5). Dissolved hydrogen in water (hydrogen water) is a portable, easily administered and safe means of delivering molecular hydrogen (6).The aim of the present prospective study was to administer hydrogen-rich water to colorectal cancer (CRC) patients treated with mFOLFOX6 chemotherapy through a randomized, single-blind, controlled clinical trial method and to compare chemotherapy-induced liver injury between treatment in control groups. Discussion Chemotherapeutic agents and their metabolites can directly induce damage to liver parenchymal cells; in addition, they may also cause additional damage to hepatocytes through cellular or humoral immunity mechanisms. There are two main categories of liver tissue damage that commonly occur as a result of chemotherapy: One is similar to non-alcoholic fatty liver disease and is often called chemotherapy-associated steatohepatitis (CASH) (9); the other results from an injury to the sinuses that causes venous congestion. Endothelial cells in the sinusoids are damaged, leading to the initiation of a coagulation cascade in the subendothelial space of Disse and ultimately to sinusoidal obstruction as fibrotic changes occur in the central venules (10).

 

Of the 136 patients enrolled in the present study, 58 (42.6%) had postchemotherapy compromise of liver function. In the majority of cases (75.9%), liver damage was grade 1-2. The mechanism underlying liver injury induced by chemotherapeutic agents is as follows: the majority of chemotherapeutic agents are metabolized in the liver; when the chemotherapeutic agent and its metabolites are beyond hepatic metabolic capabilities, electrophilic products and superoxide ions generated through the metabolic process damage hepatocellular, hepatic mitochondrial, and microsomal membranes, directly inducing hepatocellular injury through covalent binding of lipids and promotion of peroxide; in addition, drug metabolites form free radicals promoting lipid peroxidation, indirectly inducing hepatocellular injury.


Chemotherapy with mFOLFOX6 consists of 5-FU, oxaliplatin, and calcium folinate, once every 2 weeks, which is associated with a high risk of hepatotoxicity. 5-FU is converted in vivo to a triple complex that is difficult to depolymerize, including fluorodeoxyuridine phosphate, thymidylate synthase, and 5,10-citrovorum factor; it inhibits thymidylate synthase and also blocks deoxythymidylate synthesis, possibly affecting deoxynucleotide synthesis.

 

Oxaliplatin can act on DNA by generating alkylating conjugates, forming intra-chain and inter-chain cross-links, and generating cytotoxic effects. 5-FU is more associated with steatosis (11), whereas oxaliplatin regimens can result in sinusoidal damage leading to sinusoidal obstruction syndrome (12,13). 5-FU is thought to specifically affect mitochondrial membranes, allowing an increase in reactive oxygen species and triggering a cascade of events leading to lipid peroxidation, fibrosis, and cell death (14,15). Sinusoidal injury is also considered to result from reactive oxygen species. Once endothelial cells are injured, the coagulation cascade is activated and can lead to sinusoidal obstruction (16).


Several indices of liver function have been compared; postchemotherapy liver injury manifests mainly as an increase in ALT, AST, and IBIL levels, with 46 cases of ALT abnormalities, 40 cases of AST abnormalities, and 17 cases of increased IBIL levels. Considering that the patients received chemotherapy with mFOLFOX6, the postchemotherapy liver injury mainly manifested as an increase in ALT, AST, and IBIL levels.

Chemotherapeutic agents damage hepatocytes mainly by interfering with hepatocellular metabolism and oxygen free radical formation, causing hepatocellular necrosis and inflammation, or the damage is caused by hepatic fibrosis, fatty degeneration and sinusoidal obstruction. ALT and AST, which are mainly distributed in the hepatocellular cytoplasm, are the most sensitive indicators reflecting hepatocellular inflammatory injury. ALT and AST are released from damaged cells into the blood. Consequently, chemotherapy results in increased levels of liver enzymes and IBIL. ALP is increased when bile excretion is blocked with hepatocellular damage. TBIL is generated by the liver and excreted via the bile ducts; an increase in serum DBIL indicates inhibition of biliary excretion or a disturbance in hepatic bilirubin absorption and secretion. Chemotherapy does not result in inflammation or obstruction of the bile ducts, nor does it increase serum DBIL and ALP levels. However, Nakano et al reported that gemcitabine can lead to bile duct obstruction and cholestasis (17).


Some studies have shown that more than 6 cycles of chemotherapy is an independent prognostic factor for liver injury (17). In addition, patients with increased body mass, type 2 diabetes mellitus, or metabolic syndrome have an increased risk of steatosis independent of chemotherapy (18). In 2007, Ohsawa et al (19) observed that molecular hydrogen selectively reduced cytotoxic free reactive species in vitro and exerted a therapeutic antioxidant effect. Hydrogen gas (H2) has been shown to exert preventive or therapeutic effects on cerebral, myocardial, and hepatic ischemia-reperfusion injury, intestinal, pulmonary, renal, and cardiac transplantation,221 ( ). Recent basic and clinical research has revealed that hydrogen is an important physiological regulatory factor with antioxidant, anti-inflammatory, and antiapoptotic protective effects on cells and organs (22-25).


The use of hydrogen as a potential antioxidant has multiple advantages: it effectively neutralizes the hydroxy radicals present in living cells, unlike most known antioxidants that cannot successfully enter target organelles. Hydrogen has good distribution characteristics and can penetrate biomembranes and diffuse into the cytoplasm, mitochondria and nucleus of cells. Although the activity of hydrogen is weak, its fast gas diffusion properties are very effective in reducing free radical toxicity in cells. Previous studies have shown that inhalation of 1% hydrogen gas or oral administration of hydrogen-enriched water (hydrogen water) can reduce organ toxicity induced by cisplatin chemotherapy, improve quality of life, and delay weight loss without affecting the effectiveness of chemotherapy (26). As reported, hydrogen water can reduce liver injury by reducing oxidative stress and high mobility group 1 (27). In vitro experimental studies have shown that hydrogen water can reduce liver injury induced by obstructive jaundice and endotoxins (28,29).


In the present study, patients on chemotherapy who were treated with hydrogen had no significant differences in liver function parameters such as ALT, AST, ALP, IBIL, or DBIL after chemotherapy, indicating that hydrogen has a protective effect on liver function.


Hydrogen water intake is an easily available, safe, cost-effective and promising treatment. Hydrogen gas enters the human body mainly through the bloodstream and is excreted mainly by respiration, is not metabolized by the liver or kidney, and has no toxicity to the human body (30).


In the present study, hydrogen water showed good efficacy and safety in protecting liver function. However, a large number of randomized clinical follow-up studies are needed.

 

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