Nutritional supplements hold much promise in preventing cholesterol gallstones and their complications. Individuals with a high gallstone risk due to ethnicity, gender, age, family history, or other health and medical factors, and those with known silent gallstones, may want to consider supplements to possibly reduce their risk.
Vitamin C is a water-soluble vitamin that is well known for neutralizing free radicals and decreasing oxidative stress, a contributing factor in gallstone formation (Sanikidze 2016; del Pozo 2014). Vitamin C is also needed for the conversion of cholesterol into bile acids (Gaby 2009). The ability of vitamin C to prevent gallstone formation is supported by several animal studies. A relationship between vitamin C deficiency and gallstones has been recognized since the 1970s (Ginter 1971) and, for decades, low intake has been implicated in raising cholesterol saturation in the bile and in increasing the likelihood of gallstone formation (Simon 1993; Worthington 1997; Ginter 1973).
In a controlled clinical trial, 16 gallstone patients scheduled for cholecystectomy were given 500 mg of supplemental vitamin C four times daily for two weeks before surgery. Compared with similar patients who did not supplement with vitamin C, the study subjects had improved bile composition and a lengthening of the time required for cholesterol crystals to form (Gustafsson 1997). Another trial found a similar effect in 13 patients awaiting cholecystectomy who were taking 1 gram of vitamin C twice daily (del Pozo 2014). In an observational study of 2,129 subjects, regular vitamin C users were 66% less likely to have gallstones than non-vitamin C users when assessed by abdominal ultrasound (Walcher 2009). The correlation between vitamin C levels and gallstone risk appears to be stronger in women than in men (Simon 2000; Simon 1998; Ortega 1997).
Fish Oil and Omega-3 Fatty Acids
Supplementing with fish oil or omega-3 polyunsaturated fatty acids from fish (eicosapentaenoic acid [EPA] and docosahexaenoic acid [DHA]) may prevent gallstones by improving bile composition and preventing crystal formation (Berr 1992; Jonkers 2006; Cho 2015; Pasternak 2017). In a double-blind placebo-controlled trial, 35 obese women with no history of gallstones or cholecystectomy were treated with a 1,200 calorie per day diet, along with either 11.3 grams per day of omega-3 fats from fish, ursodeoxycholic acid, or placebo for six weeks. While on the diet, the time needed for cholesterol crystals to form decreased in the placebo and ursodeoxycholic acid groups, but not in the omega-3 group, suggesting fish oil may prevent the increase in gallstone risk seen with low-calorie weight loss dieting (Mendez-Sanchez 2001).
S-adenosylmethionine (SAMe) exerts protective effects on the liver and improves bile flow in people with certain liver diseases (Almasio 1990). In a preliminary study that included seven women with a history of biliary problems during pregnancy, taking 800 mg oral SAMe daily for two weeks resulted in decreased cholesterol saturation in the bile (Frezza 1988). In a trial in six healthy women who had experienced an increase in bile cholesterol saturation after starting oral contraceptives, the addition of 600 mg SAMe daily for two cycles of contraceptive use reduced this effect (Di Padova 1984).
Curcumin is a carotenoid extracted from turmeric. Several animal studies suggest curcumin may reduce the likelihood of gallstone formation by improving cholesterol and lipid metabolism (Srinivasan 2017). Curcumin has also been shown to enhance gallbladder motility (Rasyid 2002; Rasyid 1999), reduce gallbladder inflammation, and normalize bile acid metabolism (Yang 2016). In mice fed a high-fat high-cholesterol diet, curcumin protected against the development of gallstones, and its effect was enhanced with the addition of piperine, an alkaloid from black pepper (Li 2015).
Curcumin may also be helpful in recovery after cholecystectomy. In a randomized controlled trial, 50 patients undergoing laparoscopic cholecystectomy were given either curcumin or a placebo, along with standard pain relievers to use as needed, upon hospital discharge. The curcumin group had less post-operative pain and fatigue and used less pain-relieving medication than the placebo group (Agarwal 2011).
Curcumin has been shown in a few studies to promote gallbladder contraction (Rasyid 1999; Rasyid 2002). Therefore, people with a history of bile duct obstruction or who have an active obstruction should avoid curcumin.
Individuals with iron-deficiency anemia have been found to have a higher risk of gallstones than those with normal iron levels (Pamuk 2009). This relationship has been verified in the reverse as well: gallstone patients have been found to be more likely to have low serum iron levels than healthy individuals (Prasad 2015). On the other hand, concentrations of iron in the blood and bile have been reported to be significantly higher in people with pigment gallstones (Khan 2017), which are often related to conditions marked by increased red blood cell breakdown (Stinton 2012).
Iron deficiency may alter the activities of several liver enzymes, leading to increased cholesterol saturation in bile and increased cholesterol crystallization, and it also negatively impacts gallbladder motility (Prasad 2015). In addition, it is possible that gallstone disease contributes to iron malabsorption and poor iron status (Saboor 2015).
Different forms of dietary iron may have varying impacts on gallstone formation. One study followed over 44,000 men for 16 years and examined their iron consumption using a food questionnaire. Participants with the highest intake of heme iron, a well-absorbed, protein-bound form of iron found in meat and seafood, had a 21% higher risk of symptomatic gallstones compared with those with the lowest intake, but there was no significant link between the intake of non-heme iron, which is found predominantly in plant-based foods, and symptomatic gallstones (Tsai 2007). Dietary heme iron has also been shown to increase the burden of oxidative stress in the body (Romeu 2013).
Because of the role of excess iron in raising oxidative stress and the risk of cardiovascular disease, it is important to have one’s iron status assessed before taking an iron supplement (Kraml 2017). Only those with iron deficiency should consider iron supplementation to reduce the risk of gallstones.
Vitamin E is a fat-soluble nutrient that helps prevent and repair oxidative damage to lipids in the body. Vitamin E is a term that collectively refers to four tocopherols (alpha, beta, gamma, and delta) and four tocotrienols (alpha, beta, gamma, and delta), with alpha-tocopherol being the predominant form in the body (Jiang 2001; Jiang 2014). Observational studies have noted that individuals with gallstones have lower blood levels of alpha-tocopherol and alpha-tocopherol/cholesterol ratios, and lower dietary intake of alpha-tocopherol, as compared with unaffected individuals (Waniek 2018; Worthington 1997; Worthington 2004). Since oxidative stress is one of the factors believed to contribute to a higher risk of gallstones, supplementing with vitamin E may be beneficial for preventing gallstones (Waniek 2018; Sanikidze 2016).
Epigallocatechin Gallate (EGCG)
Epigallocatechin gallate, or EGCG, is a green tea flavonoid. EGCG has demonstrated gallstone-preventing effects in a mouse model of gallstone disease, possibly through its anti-inflammatory activity (Shan 2008). Findings from a population-based case-control study in China suggest drinking tea may reduce the risks of gallstone disease and gallbladder cancer (Zhang 2006). However, other research has not found a clear connection between tea drinking and gallstones (Ishizuk 2003).
Melatonin, a neuro-hormone produced in the pineal gland, may have a role in gallstone disease prevention or treatment due to its anti-inflammatory and free-radical-scavenging properties, as well as its beneficial effect on gallbladder muscle tone (Pozo 2010; Koppisetti 2008). In animal and laboratory research, melatonin has been shown to reverse age-related muscle dysfunction of the gallbladder and improve inflammation and gallbladder function in acute cholecystitis (Gomez-Pinilla 2006; Gomez-Pinilla 2007; Gomez-Pinilla 2008). In a guinea pig model, the administration of melatonin prevented the formation of pigment gallstones (Shiesh 2000).
Silymarin, a flavonoid extract from milk thistle (Silybum marianum), has been shown to counteract the negative impact of estrogen on bile flow in rats (Crocenzi 2001). Silymarin and silybin, its major active component, have also been noted to reduce bile cholesterol content in both rats and human subjects (Nassuato 1983; Nassuato 1991), suggesting its potential value in gallstone prevention and treatment.
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