What Should We Tell Our Patients About Alcohol?
Joseph Pizzorno, ND, Editor in Chief
Over the years I have written several articles about environmental toxins such as mercury and persistent organic pollutants and nutritional deficiencies such as vitamins D and K2 and iodine. The clinical applications are straightforward: decrease exposure to toxins and optimize intake of nutrients. But what about alcohol? Excess alcoholic consumption is clearly a serious clinical problem in North America, with a prevalence of lifetime and 12-month alcohol abuse of 17.8% and 4.7%, and prevalence of lifetime and 12-month alcohol dependence of 12.5% and 3.8%.1 On the other hand, teetotalers do not live as long and have a higher incidence of several diseases as those who consume light to moderate amounts of alcohol, suggesting that some alcohol is beneficial. But what is the right amount? The research is unclear and complicated.
The primary metabolic processes that regulate the rate of alcohol catabolism in normal individuals are2:
- The rate of ethanol absorption.
- The concentration and activity of liver alcohol dehydrogenase (ADH) and aldehyde dehydrogenase (ALDH).
- The reduced nicotinamide adenine dinucleotide (NADH)/nicotinamide adenine dinucleotide (NAD+) ratio in the liver mitochondria.
The availability and regeneration of NAD+ are the dominant rate-limiting factors for ethanol oxidation. Ethanol is converted to acetaldehyde by ADH, with NAD+ as a necessary cofactor. The aldehyde product of ethanol metabolism is believed to be responsible both for many of the harmful effects of alcohol consumption and for the addictive process itself. Higher than normal blood aldehyde levels have been found in alcoholics and their relatives after alcohol consumption. This suggests either increased ADH activity or depressed ALDH activity in people susceptible to alcohol dependence. Acetaldehyde is converted by ALDH to acetate, most of which is converted to long-chain fatty acids.
Nutritional and genetic factors have a huge impact on the metabolism and toxicity sensitivity to alcohol. For example, zinc is a required cofactor for both ADH and ALDH. However, ALDH is more sensitive to zinc deficiency, resulting in greater aldehyde levels after alcohol consumption with resultant increased toxicity.3 There is evolving research showing that populations susceptible to alcoholism have significant genetic variation in the activity of ADH and ALDH, such as that found in individuals of Otomi Mexican Indian ancestry.4
Excessive Alcohol Is Clearly Harmful
The health-damaging effects of excessive alcohol are substantial. As they are well-known, in the interests of space I focus here only on how to recognize alcohol abuse. There are several standards for diagnosing a patient who is consuming too much alcohol. The following are indicative of serious alcohol dependence:
- Serious symptoms when alcohol is withdrawn: tremulousness, convulsions, hallucinations, delirium.
- Alcoholic binges, benders (48 or more hours of drinking associated with failure to meet usual obligations), or blackouts.
- Evidence of alcohol-induced illnesses: cirrhosis, gastritis, pancreatitis, myopathy, polyneuropathy, cerebellar degeneration.
- Physical signs of excess alcohol consumption: alcohol odor on breath, flushed face, tremor, ecchymoses.
- Psychological/social signs of excess alcohol consumption: depression, loss of friends, arrest for driving while intoxicated, surreptitious drinking, drinking before breakfast, frequent accidents, unexplained work absences.
Some is Healthful for Most People—But How Much? The Easy Answer
A lot of research has clearly documented that light to moderate alcohol consumption provides protection from vascular and all-cause mortality, ischemic stroke, peripheral arterial disease, congestive heart failure, and recurrence of ischemic events. The generally recommended amount of “safe” alcohol consumption in healthy individuals is two standard drinks for a man and up to one drink for a nonpregnant woman.5 The form of alcohol does have an effect, with wine (which contains anti-inflammatory antioxidants like resveratrol) being clearly better than spirits or beer.6 However, there is huge individual variation in the level of alcohol consumption that causes transition from modestly helpful to seriously damaging.
There are some surprising, unexpected benefits of alcohol consumption. For example, one interesting study reported that consuming alcohol improved the efficacy of triple drug therapy for the treatment of H. pylori (omeprazole, 20 mg twice daily, clarithromycin, 500 mg twice daily, and amoxicillin, 1000 mg). Eradication was dose dependent: 70.1% in teetotalers, 79.3% in users of 4 to 16 g of ethanol a day, and 100% in users of 18 to 60 g daily.7
An unexpected problem with alcoholic beverages is factors other than its ethanol content. For example, some alcohol beverages contain surprisingly high levels of fluoride, which might be problematic for those who are sensitive to fluorides or who are already being exposed to excessive amounts of fluoride through water, tooth paste, dental applications, environmental exposure, etc.
The More Complex Answer—Personalization
The more complex answer, like everything else in biochemical individuality it seems, is to realize that some populations simply can’t drink any alcohol without immediate as well as long-term adverse events while others have substantially higher tolerance. One of the reasons for alcohol’s diverse toxic effects is not only variation in the level of the various breakdown products but also that it depletes glutathione. This results in the up-regulation of GGT (gamma glutamyl transferase) to increase resynthesis of glutathione. How about using GGT as a measure of excessive alcohol consumption?
There are some major limitations in the use of GGT as a measure of excessive alcohol consumption:
- It is also elevated by exposure to other chemicals, especially persistent organic pollutants (POPs) and several prescription drugs.
- Genetics and nutrient availability will affect its sensitivity to alcohol consumption.
- Some chronic imbibers of as much as nine drinks per day have GGT in the “normal” range.
Individuals have great variation in their ability to produce glutathione in response to toxic and oxidative challenge. Nonetheless, GGT is most effective when the patient is used as their own baseline. In a uniform population, GGT will increase in direct proportion to alcohol consumption as shown in the following figure (adapted from Nagaya T et al).8 In a nonuniform population, 40 g of ethanol per day will elevate GGT ~15% while 60 g/d for 5 weeks in young men will almost double GGT from 27 to 52 u/l. However, there is a lot of individual variation. In general, GGT goes back to “normal” after abstinence for 1 month.
So what value of GTT is indicative of excessive alcohol consumption for an individual? I could not find a specific research study answering this question. My best estimate looking at the alcohol and POP research is that a GGT above 30 clearly indicates too much chemical exposure. However, it could be as low as 25 or even 20.
Natural Health Products for Patients Consuming Alcohol
As noted above, the most toxic effects of alcohol are not due to ethanol itself but its first metabolic product, aldehyde. Fortunately, there are some natural health products we can prescribe that will help minimize the toxic effects of alcohol. However, just as prescribing supplements is not a substitute for eating a healthy diet, supplements are not a “get out of jail free card” for excessive alcohol consumption. The most important nutrients for those who abuse alcohol include the minerals magnesium, selenium, and zinc; the vitamins A, B-complex and C; and the nutrients glutamine, carnitine, and free-form amino acids.
Less understood, but with very promising evolving research, are NAC (N-acetylcysteine) and curcumin. Early research is showing that curcumin decreases the rate of alcohol absorption, decreases blood aldehyde levels, and decreases the normally resultant elevation in GGT.9 Another novel approach could be supplementation with NAC. Animal research has shown substantial protection from acetaldehyde poisoning with NAC, the efficacy of which was improved by co-administration of vitamin D and thiamin. Unfortunately, this research, which was performed over 20 years ago, does not appear to have been followed up.10
The research is clear showing that light to moderate alcohol consumption is healthful and excessive alcohol is extremely damaging to health. The challenge is that the border between healthful and toxic has huge variation based on genetics, nutritional status, and environmental toxin load. I hypothesize that one of the reasons for benefit from light to moderate alcohol consumption (separate from the antioxidant benefits of wine and the HDL elevation from ethanol) is the increased levels of glutathione that result from the induction of GGT. While most of the glutathione is being used up to detoxify alcohol and its metabolites, some is left over, resulting in increased oxidative protection within cells, especially mitochondria. No, I am not saying drink alcohol to increase glutathione! As soon as the alcohol breaches a threshold that appears to vary according to diet and genetics, cytoplasmic and mitochondrial glutathione levels plunge resulting in metabolic dysfunction and disease. It is much safer and cheaper to eat whey or take NAC. I believe that GGT might be a useful tool to personalize the guidance we give patients. Elevation of GGT (above about 30 u/l)—for whatever reason—is associated with substantial increased risk of sick days, disease (especially obesity, diabetes, and myocardial infarction) and death, an association that has been reported in the research since 1974.11 Perhaps our best measure for advising patients on their alcohol consumption is RBC glutathione, but I could not find any research.
Bottom line: it’s safest is to follow the general guidelines of one drink per day for women and two per day for men. For those unwilling to accept such limits or wanting to explore their limits, GGT monitoring might be a novel tool for providing guidance.
- Hasin DS, Stinson FS, Ogburn E, Grant BF. Prevalence, correlates, disability, and comorbidity of DSM-IV alcohol abuse and dependence in the United States: results from the National Epidemiologic Survey on Alcohol and Related Conditions. Arch Gen Psychiatry. 2007;64(7):830-842.
- Murray M. Alcohol dependence. In: Pizzorno J, Murray M. Textbook of Natural Medicine. 4th ed. Philadelphia, PA: Elsevier; 2012:1181-1188.
- Das I, Burch RE, Hahn HK. Effects of zinc deficiency on ethanol metabolism and alcohol and aldehyde dehydrogenase activities. J Lab Clin Med. 1984;104(4):610-617.
- Montano Loza AJ, Ramirez Iglesias MT, Perez Diaz I, et al. Association of alcohol-metabolizing genes with alcoholism in a Mexican Indian (Otomi) population. Alcohol. 2006;39(2):73-79.
- Di Minno MN, Franchini M, Russolillo A, Lupoli R, Iervolino S, Di Minno G. Alcohol dosing and the heart: updating clinical evidence. Semin Thromb Hemost. 2011;37(8):875-884.
- Lippi G, Franchini M, Favaloro EJ, Targher G. Moderate red wine consumption and cardiovascular disease risk: beyond the “French paradox”. Semin Thromb Hemost. 2010;36(1):59-70.
- Baena JM, López C, Hidalgo A, et al. Relation between alcohol consumption and the success of Helicobacter pylori eradication therapy using omeprazole, clarithromycin and amoxicillin for 1 week. Eur J Gastroenterol Hepatol. 2002;14(3):291-296.
- Nagaya T, Yoshida H, Takahashi H, Matsuda Y, Kawai M. Dose-response relationships between drinking and serum tests in Japanese men aged 40–59 years. Alcohol. 1999;17(2):133-138.
- Shimatsu A, Kakeya H, Imaizumi A, et al. Clinical application of “curcumin”, a multi-functional substance. Anti Aging Med. 2012;9(1):43-51.
- Sprince H, Parker CM, Smith GG, Gonzales LJ. Protective action of ascorbic acid and sulfur compounds against acetaldehyde toxicity: implications in alcoholism and smoking. Agents Actions. 1975;5(2):164-173.
- Whitfield JB. Gamma glutamyl transferase. Crit Rev Clin Lab Sci. 2001;38(4):263-355.