Life Extension Magazine

Life Extension Magazine November 2005

Report

A Little-Known Fact: Alcohol is a Carcinogen!

By Dale Kiefer

By Dale Kiefer

Liver cancer cells. These cancerous cells have large nuclei (pale purple), very little cytoplasm (orange, yellow), and are undergoing chaotic division.

Alcohol and the Liver

During first-pass metabolism of alcohol, the coenzyme nicotinamide adenine dinucleotide (NAD) is converted to its reduced form, NADH. NAD and NADH are compounds involved in the synthesis of the energy molecule adenosine triphosphate (ATP) within the mitochondria. Production of excess NADH upsets the delicate reduction/oxidation, or redox, balance in liver cells.

Excess alcohol ingestion promotes fatty acid synthesis, causing a rise in liver fatty acid content. This saturates the liver with lipids, causing “fatty liver,” or steatosis, a first step on the path to more serious liver disease. Elevation of blood lipids, including high-density lipoprotein (HDL), may also occur.23

In recent years, the mild increase in HDL induced by alcohol has been touted as playing a beneficial role in the reduction of cardiovascular disease and incidence of stroke.23 But alcohol’s other effects are less benign.

The acetaldehyde produced during alcohol metabolism is a mutagenic agent, capable of producing harmful genetic mutations that may trigger various cancers.45-47 Some of alcohol’s worst effects, however, are caused by the free radicals produced as a result of its metabolism. These rogue molecules steal hydrogen ions from fatty acids in the cell membranes, triggering a chain reaction that damages or destroys cell membranes, a process referred to as lipid peroxidation.48

Metabolism of alcohol provokes a striking increase in the activity of cytochrome P450 liver enzymes, especially a subset enzyme known as 2E1. Studies show that 2E1 liver enzymes are four to 10 times higher in people who have recently

consumed alcohol than in non-drinking controls. This liver enzyme converts various compounds to highly toxic metabolites. One consequence of drinking, therefore, is the production of toxic metabolites that would otherwise not occur. For example, many pesticides are normally converted to non-carcinogenic compounds in the livers of non-drinkers. But among alcohol drinkers, they are converted to carcinogens—compounds known to have cancer-promoting properties.47

Glutathione and N-acetylcysteine

Glutathione, one of the body’s most important natural antioxidants, plays a key role in alcohol detoxification. In the liver, glutathione binds to toxins and transforms them into compounds that can be excreted in the bile or urine. The liver’s supply of glutathione may be exhausted by binding to carcinogens produced during alcohol detoxification by the liver. The direct conjugation of acetaldehyde and glutathione has been observed in acute models of alcohol ingestion. When depleted by chronic alcohol ingestion, glutathione becomes unavailable for ordinary regulatory processes.

N-acetylcysteine is an antioxidant supplement that has been shown to help restore depleted glutathione levels.49 Studies in rats suggest that oral glutathione supplementation may restore glutathione levels that have been depleted by toxins.50,51 Preventing glutathione depletion is important in preventing alcoholic hangover and averting the damaging effects of even moderate amounts of alcohol.

Vitamin C

Vitamin C is one of the essential nutrients depleted by alcohol consumption.52 Because it is the body’s primary water-soluble dietary anti-oxidant, this depletion results in severe oxidative stress in daily drinkers.42 Vitamin C is also an essential co-factor for many enzymes, and its depletion lowers levels of internally produced antioxidant enzymes such as superoxide dismutase (SOD), catalase, and glutathione peroxidase.53 Low levels of these antioxidants may be associated with increased rates of cancers in humans, whether or not they consume alcohol.54

Vitamin C protects human brain cells against the damaging effects of alcohol exposure in several ways. Although alcohol increases brain cell levels of inflammatory mediators such as COX-2 and PGE-2, these remain at low levels when adequate vitamin C is present. Scientists have shown that brain cells enriched with vitamin C contain low levels of heat shock protein, even after exposure to alcohol. But cells not enriched with vitamin C produce high levels of heat shock protein upon exposure to alcohol.55 Heat shock protein activates glial cells, which damage other human brain cells when both are exposed to alcohol. Heat shock proteins are overexpressed in vascular disease and spinal disease, and appear to be involved in the death execution pathways of brain cells (apoptosis).56,57 Vitamin C supplementation is essential to protecting brain cells against oxidative damage caused by alcohol exposure.

Vitamin E

Vitamin E is the most vital fat-soluble antioxidant and complements vitamin C and the important liver antioxidant glutathione.

Vitamin E, which comprises eight structurally related tocopherols and tocotrienols, is capable of numerous actions within the body.58 As an antioxidant, it imbeds itself in the fat-soluble portions of cell membranes, where it counters free radical reactions in the fatty acid chains that are critical to the architecture and proper functioning of the membranes.

Vitamin C regenerates vitamin E back to its reduced form, so that vitamin E, once spent, is able to rejoin the fray.59-61 Brain and liver cells contain the lion’s share of lipids among the body’s organs, and lipid peroxidation rates are highest in the brain and liver due to their fat content. Accordingly, vitamin E content is also highest in these organs. Alcohol contributes heavily to lipid peroxidation in both organs.58,62,63 Nature has tailored vitamin E to block the peroxidation process, thus explaining its concentration in these two organs and its depletion by alcoholism and cirrhosis.53,62,64 Vitamin E is an essential nutrient that may prevent damage caused by alcohol in the brain and liver.65,66 As such, it is a supplement that should always be taken by those who consume alcohol.

Micrograph of crystalline thiamine, vitamin B1 magnified 30 times.

Thiamine and Benfotiamine

Thiamine (vitamin B1) is an essential water-soluble vitamin. Thiamine deficiency can cause lethargy, fatigue, apathy, impaired awareness, loss of equilibrium, disorientation, memory loss, anorexia, muscular weakness, and eventually death.67 Alcohol consumption depletes thiamine and produces the same symptoms as non-alcoholic thiamine deficiency.68 Thiamine deficiency damages brain cells and other nerve cells throughout the body. Thiamine deficiency—rather than the toxic effects of ethanol—has been proposed as the primary cause of cerebellar degeneration in alcoholics.69

Allithiamines are naturally occurring fat-soluble thiamines that have demonstrated a superior ability to penetrate cell membranes. The most common allithiamine, benfotiamine, has much greater bioavailability than thiamine. Benfotiamine prevents glucose from reacting with proteins in the body to form potentially harmful compounds called advanced glycation end products.70 Blocking this process helps preserve the structure and function of retinal, nerve, kidney, and other cells.

Studies have shown that benfotiamine completely blocks advanced glycation end products from forming, while thiamine has no such effect. One study concluded that benfotiamine supplementation is absolutely essential for patients suffering from chronic alcohol abuse.71 Other studies have shown that benfotiamine increases thiamine status much more effectively than thiamine supplementation alone after chronic alcohol use.72 Supplementing with both fat-soluble benfotiamine and water-soluble thiamine therefore is essential to preventing some of chronic alcohol consumption’s most damaging effects.

Chlorophyllin

Chlorophyllin, a water-soluble form of the green plant pigment chlorophyll, is among the most powerful gene protectors—or antimutagenic agents—ever discovered. Used extensively as a food colorant, it has numerous medicinal applications and has proven to be an effective anti-carcinogen in animal models of liver cancer.73 Chlorophyllin is an “interceptor molecule” that bonds to the carbon-chain backbone of hydrocarbon carcinogens and allows them to be excreted in the feces.74 It has been shown to be effective at the extremely low dose of 1 mg per kilogram of body weight in both animal and human studies. (It is rare to find a supplement for which the doses used in animal studies are virtually identical to the doses found to be effective in humans.)

In numerous human and animal studies, chlorophyllin has been shown to protect the liver against environmental carcinogens and those produced by the liver itself.74 Chlorophyllin also acts as an antioxidant, protecting mitochondria against oxidative damage induced by various reactive oxygen species, and inhibiting lipid peroxidation.75

Middle-aged people at high risk of contracting liver cancer served as subjects in a landmark Chinese study that demonstrated chlorophyllin’s remarkable protective effects against liver-activated dietary carcinogens. This randomized, double-blind, placebo-controlled chemoprevention trial tested whether chlorophyllin could affect levels of the dietary toxin aflatoxin in the subjects’ livers. Nearly 200 adults were randomly assigned to ingest 100 mg of chlorophyllin or a placebo three times daily for four months. Subjects who took chlorophyllin lowered their load of the studied carcinogen by 55%. The investigators estimated that this could help protect these adults from developing cancer for 20 or more years beyond the age when liver cancer commonly occurs, thus extending life significantly in this Chinese population.76 In several studies, chlorophyllin has also been shown to protect against the harmful chromosome-breaking and mutating effects of commonly used pesticides and chemotherapy drugs. This is notable, as alcohol may induce the liver to metabolize pesticides into considerably more toxic compounds than it would otherwise normally do.77-80