Alcohol: Reducing the Risks
Chronic alcoholism causes impaired B vitamin absorption and is well known to cause vitamin B1 (thiamine) deficiency, which can lead to serious neurological and cardiovascular problems (Day 2013; Portari 2013; Said 2011). Benfotiamine is a synthetic, fat-soluble form of thiamine found to have higher bioavailability than water-soluble thiamine supplements in humans (Xie 2014; Park 2016; AMR 2006a). In animal research, benfotiamine was more effective than thiamine at raising thiamine levels after acute alcohol intoxication (Portari 2013; AMR 2006b). An eight-week randomized controlled trial in 84 patients with severe alcoholic polyneuropathy found that treatment with 320 mg benfotiamine per day for four weeks followed by 120 mg per day for four weeks improved neuropathy symptoms (Woelk 1998; AMR 2006a). Another study showed benfotiamine treatment reduced psychiatric distress in men with longstanding severe alcohol use disorder (Manzardo 2015).
Nicotinamide riboside is a form of vitamin B3 that acts as a precursor to nicotinamide adenine dinucleotide, NAD+, a necessary cofactor for many metabolic processes (Chi 2013; Trammell 2016). Depletion of NAD+ in alcohol metabolism, resulting in a lower NAD+/NADH ratio, has been suggested to be a contributing factor in alcohol toxicity (Cederbaum 2012). Supplementing with nicotinamide riboside has been found to raise blood concentrations of NAD+ in humans (Trammell 2016) and demonstrated neuroprotective effects in animal studies (Chi 2013).
Vitamin B6 and related compounds may also offset some of the negative effects of alcohol consumption (Khan 1973).
Alcoholics have low folate levels, which likely results from decreased absorption from the small intestine; altered liver metabolism and retention of folate; elevated excretion of folate in the urine; and disturbed folate metabolism after alcohol ingestion (Medici 2013). Thus, folate supplementation should be considered by people who regularly consume alcohol.
Clove Bud Extract
Clove bud is a rich source of polyphenols (Issac 2015). An unpublished randomized, crossover trial in 14 subjects found that a single dose of 250 mg of clove bud extract taken before drinking alcohol led to lower blood alcohol and acetaldehyde concentrations, and less depletion of detoxification enzymes, compared to a control group. Furthermore, those taking clove bud extract experienced less severe hangover symptoms (Spiceuticals 2015). A study in 26 healthy individuals found that consumption of 250 mg of a clove bud extract for 30 days led to increased levels of several endogenous antioxidants, including glutathione, resulting in a reduction in oxidative stress (Johannah 2015). In a rodent study, pre-treatment with clove bud extract protected the stomach linings of rats exposed to high amounts of alcohol for three days. Clove bud extract treatment was also associated with higher levels of gastric glutathione and gastro-protective prostaglandins, and improvement in other markers of oxidative stress (Jin 2016). In another rodent model, rats treated with clove bud extract had increased stomach mucus production and were protected against alcohol-induced stomach ulcers (Santin 2011). Clove bud extracts have also been shown, in a laboratory and rodent study, to have immunomodulatory, anti-inflammatory, and liver-protective effects (Dibazar 2015; El-Hadary 2015).
N-acetylcysteine (NAC) is a form of the amino acid cysteine, which is a precursor to the endogenous antioxidant glutathione, along with the amino acids glutamate and glycine. NAC directly binds acetaldehyde (McCarty 2013; Vasdev 1995). In animal research, NAC has been found to reduce alcohol toxicity (McCarty 2013). In a mouse study, the combination of NAC and vitamin C modified the activity of detoxification enzymes and reduced the production of free radicals triggered by alcohol (Leung 2015). In another rat study, administration of NAC resulted in lower levels of alcohol-induced oxidative stress in brain and liver tissues (Ozkol 2016).
Glutathione, an important detoxification compound and antioxidant, is found in cells throughout the body and is highly concentrated in the liver (Chen 2013). Alcohol reduces glutathione levels in the liver, which can lead to liver cell injury and contributes to the development of alcoholic liver disease (Lieber 2003). In a rat study, two weeks of glutathione administration before alcohol exposure led to more efficient clearing and lower peak blood levels of both alcohol and acetaldehyde. Even rats given high-dosage glutathione after alcohol exposure experienced faster clearance of alcohol and acetaldehyde, and lower levels of oxygen free radicals than control rats given water only (Lee 2009).
Moderate alcohol consumption has been shown to cause vitamin E status to deteriorate in men (Addolorato 2008) and postmenopausal women (Hartman 2005). One rat study found that gamma-tocopherol in particular was depleted by alcohol consumption (Sadrzadeh 1994). Gamma-tocopherol is one of eight compounds (four tocopherols and four tocotrienols) that together comprise the vitamin E family; gamma-tocopherol is the most common form of vitamin E in food (Dietrich 2006).
Several animal studies have shown that vitamin E treatment decreases markers of chronic alcohol-induced inflammation, oxidative stress, and tissue injury (Das 2010; Sajitha 2010; Kaur 2010; Lee, Kim 2013; Shirpoor 2016). One animal model showed that vitamin E prevented oxidative stress and glutathione depletion after acute alcohol exposure, and this effect was enhanced by concomitant treatment with methylselenocysteine, a form of selenium (Yao 2015). Two additional animal studies found tocotrienols may protect against alcohol-related neurotoxicity (Tiwari 2009; Tiwari 2012).
The trace mineral selenium is needed for the proper function of the glutathione peroxidase antioxidant system, and low selenium levels have been observed in people with alcoholic liver disease (Rua 2014). Findings from animal research suggest episodes of heavy drinking can cause a decrease in blood and liver selenium levels, resulting in lower glutathione activity and greater oxidative stress (Ojeda 2015). Other research shows selenium supplementation may prevent these negative effects (Markiewicz-Gorka 2011; Ozkol 2016; Yao 2015).
Grape Seed Extract
Grape seeds and skins are a rich source of polyphenolic compounds called proanthocyanidins. These compounds are strong neutralizers of tissue-damaging oxygen free radicals (Dogan 2012). In one controlled animal study, rats pre-treated for seven days with grape seed polyphenols prior to acute heavy alcohol exposure experienced a less pronounced rise in blood alcohol and acetaldehyde levels; increased production of endogenous enzymes that protect against oxidative stress; and less of an increase in markers of liver cell damage (Bak 2016). This suggests grape seed polyphenols may mitigate some of the effects of alcohol that contribute to hangover symptoms. In other animal studies, grape seed extract prevented neuronal and liver injury and improved markers of oxidative stress after prolonged alcohol administration (de Freitas 2004; Dogan 2012; Assuncao 2007).
Resveratrol is a polyphenolic compound found in red wine and the roots of the traditional Asian medicinal plant Polygonum cuspidatum (Japanese knotweed), as well as peanuts, grape skin, and blueberries (Higdon 2015). A wealth of animal research suggests resveratrol may help minimize oxidative stress and related inflammation and tissue damage seen with long-term alcohol consumption (Kasdallah-Grissa 2007; Ajmo 2008; Bujanda 2006). In other animal studies, resveratrol prevented both the loss of learning capacity (Tiwari 2013b; Ranney 2009) and rises in markers of oxidative stress and inflammation observed with chronic alcohol exposure; higher doses of resveratrol were associated with greater protection (Tiwari 2013b).
Extracts of picrorhiza (Picrorhiza kurroa) have shown liver-protective, immune-modulating, anti-inflammatory, and free-radical-scavenging activities (Kant 2013) that could be helpful in preventing hangover and other problems related to alcohol use. Animal research provides support for picrorhiza’s potential to protect against alcohol-related liver damage. In two studies, a picrorhiza root extract prevented liver cell damage in rats chronically fed alcohol. In one of these studies, the extract also reversed alcohol’s negative effect on the alcohol-metabolizing enzymes alcohol dehydrogenase and acetaldehyde dehydrogenase, and on bile acid and bile salt production in liver cells (Saraswat 1999; Rastogi 1996).
Vitamin C has shown potential as an anti-hangover agent by preventing oxidative stress in the livers of alcohol-fed mice. Vitamin C administration restored liver glutathione levels to normal after alcohol feeding, and blunted alcohol-induced oxidative stress compared with alcohol-fed mice that did not receive vitamin C (Lu 2012). Other studies in rats have suggested vitamin C may protect against alcohol-related tissue damage in neurons (Ambadath 2010), kidneys, and blood vessels (Sonmez 2012; Sonmez 2009).
Silymarin, an extract of milk thistle (Silybum marianum) fruit, contains a mixture of flavonoids of which 50–70% is typically silybin (Loguercio 2011). Silymarin and silybin are used mainly to treat conditions of the liver (Federico 2017). Early clinical research suggests milk thistle extracts may reduce damage due to alcoholic cirrhosis. Silymarin and silybin can increase glutathione levels, and animal studies show they activate detoxifying enzymes depleted by alcohol, improving mitochondrial function and moderating alcohol-related liver damage (Federico 2017; Loguercio 2011; Vargas-Mendoza 2014). Silymarin may also protect neurons by decreasing inflammation and oxidative stress in the nervous system (Borah 2013).
Chronic excessive alcohol intake is correlated with bacterial overgrowth in the small intestine and changes in the bacterial population of the large intestine. In addition, alcohol increases permeability of the intestinal lining, allowing bacterial toxins to be absorbed, causing inflammation in the liver and other tissues. Indeed, these effects are now thought to be a major contributor to alcoholic liver disease (Li 2016; Engen 2015; Malaguarnera 2014). In a clinical trial, 66 men suffering from alcoholic psychosis were given a probiotic supplement, with or without standard therapy of abstinence from alcohol plus a multivitamin, for five days. The probiotic contained 90 million colony-forming units of Bifidobacterium bifidum and 900 million colony forming units of Lactobacillus plantarum. After just five days of treatment, those who had received probiotics showed some resolution of liver damage, as evidenced by greater reductions in levels of liver enzymes (markers of liver damage); they also showed restoration of healthy intestinal bacteria (Kirpich 2008). Another trial in 117 hospitalized patients found that a abstaining from alcohol and supplementing with a probiotic containing Lactobacillus subtilis and Streptococcus faecium for seven days led to greater improvement in intestinal bacteria and reductions in levels of bacterial toxins and inflammatory cytokines compared with placebo and abstinence (Han 2015).
Further support for the potential role of probiotics in alcohol recovery comes from animal studies that found supplementation with Lactobacillus and Bifidobacterium species may protect against damage to the stomach, such as may be caused by alcohol, through a number of different mechanisms. These include an increase in gastric mucous production and a reduction of gastric inflammation (Suo 2016; Gomi 2013; Khoder 2016), reduced gut hyperpermeability (Wang 2011), and protection against alcohol-related liver cell inflammation and injury (Barone 2016; Tian 2015; Shi 2015; Chiu 2014; Chang 2013; Wang 2013; Bull-Otterson 2013).
Polyenylphosphatidylcholine (PPC) is a mixture of phospholipids found in animal studies to reduce free radical production and prevent alcohol-induced oxidative damage to liver cells (Lieber 2003; Mi 2000; Baraona 2002). In one study, PPC prevented alcohol-induced depletion of liver S-Adenosyl Methionine (SAMe), which was associated with preservation of liver glutathione levels in rats (Aleynik 2003). Phosphatidylcholine, a particular phospholipid in PPC, has been found to prevent alcohol-induced liver fibrosis and cirrhosis in baboons (Lieber 1994). In a subgroup of chronic drinkers who participated in a clinical trial, PPC treatment mitigated the increases in liver enzymes and bilirubin that occurred during the trial; these markers are indices of liver impairment. The participants took 1.5 grams of PPC three times daily, before meals (Lieber, Weiss 2003).
Alcohol consumption rapidly triggers magnesium loss from tissues including the brain and liver. Under the influence of alcohol, this magnesium is lost in the urine, resulting in a tendency towards decreased serum magnesium (Rivlin 1994; Torres 2009; Romani 2008). The resulting overall reduction in magnesium availability causes blood vessels to constrict and may help explain associations between excessive alcohol consumption and hypertension, cardiac problems, and stroke (Romani 2008; Moulin 2015). One clinical report described low blood magnesium levels in five individuals with alcohol-induced headache and hangover, which was successfully treated with intravenous magnesium (Altura 1999). A form of magnesium called magnesium-L-threonate has been shown to elevate brain magnesium levels in animal research. This may represent a strategy for combatting alcohol-induced depletion of brain magnesium, although this has yet to be demonstrated in a clinical trial (Jia 2016).
Lipoic acid is a sulfur-containing compound that increases glutathione levels and neutralizes some types of free radicals (Higdon 2012; Golbidi 2011). Lipoic acid also participates in the recycling of vitamins C and E, mitigates inflammation (Moura 2015), and has been shown in laboratory settings to increase the activity of aldehyde dehydrogenase, which breaks down acetaldehyde (McCarty 2013; Li 2013).
In animal research, rats and mice given lipoic acid showed less motivation to consume alcohol (Peana 2013; Ledesma 2014), and mice treated with lipoic acid before alcohol consumption had lower levels of free radicals in their brain tissue, and showed less alcohol-induced behavioral problems than those treated with alcohol alone (Ledesma 2012).
Melatonin is a hormone that helps regulate circadian rhythms and induce sleep (Lanfumey 2013), and both drinking and withdrawing from alcohol appear to suppress melatonin production (Schmitz 1996; Peuhkuri 2012). In one animal study, muscle coordination was better during the hangover time period in mice given melatonin for seven days before being exposed to an intoxicating amount of alcohol (Karadayian 2014). Because sleep disturbance appears to be an important factor in alcohol hangover symptoms and severity (Verster 2014; Rohsenow, Howland 2010), improving sleep quality may be a mechanism by which melatonin could reduce some hangover symptoms. In addition, melatonin has a number of other effects that could help prevent hangover and other harms due to alcohol: It modulates the inflammatory response, prevents oxygen-related cellular damage, and may have analgesic effects (Danilov 2016; Hu 2009).
Panax ginseng, also known as Korean or Red Ginseng, is a medicinal plant historically used to treat fatigue, increase energy, and build stamina and resilience (Kim 2013; Ong 2015). A study on 25 healthy men compared the effect of taking 32 mg of a Panax ginseng root extract dissolved in water along with 100 milliliters of 80 proof whiskey to plain water with the same amount of whiskey. Participants experienced less fatigue, fewer cognitive symptoms, less thirst, and fewer stomach aches after taking ginseng with whiskey than after whiskey and water alone (Lee, Kwak 2014).
Findings from animal research suggest Panax ginseng and its constituents reduce alcohol-related tissue injury by inhibiting oxygen free radical activity and inflammation (Li 2014; Gao 2015), and possibly by increasing rates of alcohol and acetaldehyde clearance from the body (Lee, Kim 2014). In mice, even with acute heavy alcohol exposure, pretreatment with Panax ginseng for seven days reduced liver damage (Ding 2015).
Important active constituents of Panax ginseng called ginsenosides are poorly absorbed in their natural state. However, fermentation has been shown to increase the bioavailability and serum concentration of ginsenosides by about 15 fold. Thus, a fermented Panax ginseng formulation may be a superior choice when considering a ginseng supplement (Jin 2012).
Curcumin, a polyphenolic compound found in the culinary spice turmeric root, has potent anti-inflammatory properties (Gupta 2013). In a preliminary study, seven healthy men drank alcohol with either water alone or a preparation of curcumin and water. Blood acetaldehyde levels were significantly lower in the curcumin group (Sasaki 2011). Also, several animal studies suggest curcumin can reduce alcohol-related oxidative stress, inflammation, and tissue injury (El-Deen 2010; Kandhare 2012; Pyun 2013; Rong 2012; Tiwari 2013a; Varatharajalu 2016).
Taurine is a sulfur-containing amino acid with multiple functions throughout the body, including in the central nervous and cardiovascular systems (Oja 2007). Supplemental taurine, in combination with medicinal herbs, administered to mice exposed to a high amount of alcohol increased their rate of alcohol metabolism, lengthening time to become intoxicated and shortening recovery time (Wu 2013). Taurine also prevented hypertension in rats given large amounts of alcohol for four weeks (Harada 2000). In another study, zebrafish briefly exposed to a single high dose of alcohol had lower brain alcohol levels and showed less anxious behavior if they also received taurine (Rosemberg 2012). Various other animal studies show taurine may prevent alcohol toxicity by reducing oxidative stress, inflammation, and tissue injury (Devi, Anuradha 2010; Devi, Viswanathan 2010; Latchoumycandane 2014).
S-adenosyl methionine (SAMe) is critical to the formation of the cellular antioxidant glutathione, and also participates in methylation pathways that neutralize homocysteine, a cellular toxin. Alcohol disrupts SAMe formation, and liver SAMe concentrations are depleted in patients with alcoholic liver disease. Fortunately, SAMe supplementation has been found to improve liver function in alcohol-exposed animals and alcoholic humans (Lieber 2003). Investigation using an animal model found SAMe may protect the liver against toxic effects of alcohol in part by improving mitochondrial function in liver tissue (King 2016), in addition to facilitating glutathione synthesis.
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