Alcohol+and+Training

Ethanol, aka "alcohol", is perhaps the most widely consumed drug o­n Earth. With the exception of its effects o­n heart disease, few people would claim it is good for you. But, because of its legality, omnipresence, and just the fact that it is so much fun, most think very little of having a few beers or even a few six packs. This includes many bodybuilders.

However, it is far from being a harmless vice, even in non-alcoholics. It affects numerous neurotransmitters, metabolic processes, and hormones -- and many of these effects go beyond the time period of intoxication. These have ramifications, not o­nly for general health, but as you will see, body composition as well.

This is the first of a two parts series -- We will first look at the basic science of ethanol, then we will turn to its effects o­n body composition in the second installment. We will not be looking at the effects of chronic ethanol consumption, addiction, and withdrawal, as they are not relevant to what I consider as my target audience. Suffice it to say, such a lifestyle is utterly incompatible with getting the most out of o­ne's bodybuilding efforts.


 * Biochemistry**

Ethanol, in addition to being a drug, is also a nutrient (1). However, unlike the other nutrients such as carbs, fat and protein, the body lacks the ability to store ethanol (1) -- It is also the o­nly toxic macronutrient (1). These two characteristics lead to some important consequences -- namely, it must be metabolized, and this metabolism take precedence over all other nutrients (2).

It is metabolized by o­ne of two pathways, depending o­n blood levels. The primary is to aldehyde, via alcohol dehydrogenase (ADH) (3). However, at high levels, what is known as the microsomal ethanol oxidizing system (MEOS) becomes a significant pathway (4). Both result in conversion to acetate, then acetyl-CoA -- where it can either a) enter the tricarboxylic acid cycle and be oxidized into CO2 and water, or b) be stored a fat (1).


 * Pharmocokinetics**

Ethanol is readily bioavailable with oral administration, however, oral clearance rate and % absorption decrease in the post-prandial state (i.e. with food) (5), due to the presence of ADH activity in the stomach (6). The more food in the stomach, the longer the ethanol stays there to be metabolized before it reaches the bloodstream. The type of food will effect this, with protein and fat have the greater effect. Fat, due to slowing transport into the small intestine, protein, probably through direct binding with the ethanol molecule (7).

The type of drink can also effect blood alcohol levels obtained - particularly in the fed state. For instance, after a meal, a less concentrated drink (such as a beer) will be absorbed more quickly than a more concentrated o­ne (such as a shot) -- and, in rats, this led to an 80% higher peak blood alcohol level and 95% higher overall absorption (8). However, o­n an empty stomach, the opposite was found, though the magnitude of the difference was not as strong.

It is also interesting to note that when large amounts are taken in, absorption can exceed systemic distribution, thus exceptionally high concentrations can occur in arterial blood, and, therefore, the brain (7). This is why bonging 6 beers right in a row hits you harder than drinking 8 drinks over 2 hours.

Despite popular opinion to the contrary, women do not metabolize ethanol more slowly than men - the opposite is in fact true. Failure to take into account differences in total body water (i.e. LBM) between men and women has accounted for much of this confusion (9). But, when normalized for total body water, women metabolize ethanol 33% faster than men, due to a proportionally larger liver (10).

Due to limitations of ADH, metabolism of ethanol follows zero-order, straight line kinetics - meaning it is broken down at a constant rate (about a drink per hour) rather than having a half-life as most drugs do (11).

DHT has been shown to decrease breakdown of ethanol by increasing the breakdown of ADH, thus a good testosterone cycle will increase susceptibility to intoxication (12).

Aldehyde, as mentioned, is a product of ethanol metabolism. In the literature, its presence has generally been found to produce an aversive response, thus the basis of treatment of alcoholics with disulfiram (13). It is responsible for the flushing seen in some drinkers, usually Asians -- this can be reduced with the use of antihistamines (14). However, a few studies have shown it to be involved in the reinforcement of ethanol intake (15).

Aldehyde is also implicated in ethanol's hepatotoxic effects (16). The amino acid taurine enhances the metabolism of aldehyde by activating the hepatic enzyme aldehyde dehydrogenase, thus lowering levels -- though this was with the equivalent of 45 grams for a 200lb person (17), so who knows if supplementing with reasonable levels would be effective.


 * Pharmacology**

Following oral, intravenous, or intraperitoneal administration, ethanol produces central nervous system (CNS) effects of a biphasic nature. Lower concentrations (10-25mM -- 3 to 8 drinks) tend to produce stimulant effects (euphoria) while higher doses result in CNS depression (anti-anxiety, sedation) (18).

It was thought for quite some time that ethanol produce its effects through nonspecific means, by acting as a solvent, or interfering with lipid membranes (19, 20). In fact, as late as a 1997 drug education class I took in college, we were informed that it worked by coating the cells rather than interacting with specific receptors like all other drugs. This view has recently fallen out of favor for several reasons that I won't go into detail o­n, and it is now considered to exert its effects through binding to proteins o­n specific receptors (21). It is widely held that no specific ethanol receptor exists, though o­ne prominent researcher suggests that the evidence suggests we should be moving toward the concept of a specific ethanol receptor (22).

The exact mechanism behind its subjective effects are still not completely understood, and involve multiple neurotransmitter systems and ion channels with many studies reporting effects that completely contradict other o­nes, and all of this is further complicated by the fact that ethanol seems to preferentially affect certain subtypes of the various receptors. An exhaustive presentation is best suited for a 500 page book, thus I have weeded through and analyzed the research in order to give what I consider the best overall generalization about its effects o­n the various systems.


 * Dopamine**

Levels of the central neurotransmitter dopamine have been consistently shown to be increased by ethanol (23,24), and it is considered as the primary mediator of the reinforcing effects of all drugs of abuse (25). It is also involved in behavioral reinforcement in general. Of particular importance is the mesolimbic dopamine system, which is regulated by neurons in the Ventral Tagamental Area (VTA) and Nucleus Accumbens (NAC) (26).

Alcohol-preferring rats have been shown to have lower basal mesolimbic dopaminergic activation and innervation than non-preffering rats (27) -- as well as altered serotonin, GABA, and opioid activity, all of which are major modulators of the mesolimbic dopamine system and likely contribute to the hypofunctioning of this area (27, 28). Acute administration of ethanol increases extracellular dopamine levels in the NAC as a result of increased firing of dopamine neurons in the VTA, thus bringing mesolimbic activity toward normal (29). Thus, ethanol intake is merely representing self-medication -- bringing about behavioral activation (thought analogous to euphoria in humans) and decreased anxiety in alcohol-preffering rats, while non-preferring rats, whose dopamine system is not faulty, tend to just become sedated (27).


 * Opiod**

Ethanol has been found to increase brain levels of the endogenous opioid beta-endorphin (31), and it is likely that the opioid system mediates a large part of its effects o­n dopamine levels, by removing GABA mediated inhibition of dopamine neuron firing (32).

It has been found that alcoholics have lower basal levels of endogenous opioids than non-alcoholics, and when ethanol is consumed these levels increase to a level higher than those reached by non-alcoholics with ethanol consumption (33). Opiod receptor antagonists have been found to inhibit the reinforcing effects of ethanol in animals and the euphoric effect in humans (34). o­ne of these, nalaxone, is considered a very promising drug in the fight against ethanol addiction.

However, if I may opine for a moment, I would like to point out that opioids are the brain's happy hormones, so alcoholics are self medicating to bring themselves happiness that the biochemistry of their brain withholds from them, so a drug that keeps someone from drinking by making it ineffective at making them happy seems a piss poor approach to me. But, of course, they would never allow a long-acting morphine for such purposes, because, heaven forbid, someone might want a little more happiness than The Man deems appropriate and thus might "abuse" it.


 * NMDA**

The NMDA receptor is o­ne of three types of glutamate receptors -- the body's primary excitatory neurotransmitter. It is named for n-Methyl-d-Aspartate, its synthetic, high-affinity ligand (35). Ethanol has been found to block the action of this receptor (36). The likely mechanism is by preventing glutamate's removal of a magnesium ion which blocks calcium influx into the cell (37). This decreases the excitation of the cell, which, along with increased inhibition via GABA, results in the sedative-depressant effects of ethanol, particularly at higher doses.

This blockade leads to upregulation of glutamate receptors (38), which leads to hyperexcitability of the cell when ethanol is no longer present -- this is o­ne of the mechanisms responsible for ethanol induced neurotoxicity seen with withdrawal (39). It has also been postulated that the end of each drinking episode represents a mini-withdrawal complete with the aforementioned excitotoxicity (40). Because magnesium is the natural antagonist for the receptor (41), it would probably not be a bad idea to take 400-800 mg before bed after a night of drinking. Zinc, and the amino acid taurine may be as well (42,43).

By the way, magnesium and zinc's antagonism of the NMDA receptor may account for ZMA's positive effects o­n sleep. Unfortunately, it is disruption of the NMDA receptor that leads to the decrease in REM sleep caused by alcohol (43b).

The NMDA receptor complex is also implicated in memory loss and blackouts from ethanol (35) -- This is due to its effects o­n long-term potentiation (LTP). We will address this in more detail later.


 * GABA**

Another very important system is the gamma-aminobutyric acid (GABA) system -- the body's primary inhibitory pathway (44). Ethanol potentiates GABA's activity at its receptor (45). It likely has a biphasic effect on behavior, with lower doses inhibiting inhibitory GABA interneurons on dopamine receptors in the VTA -- thus causing dopamine induced stimulation and euphoria, and higher doses producing widespread inhibition of CNS activity, thus overriding the stimulant effects (46, 47). This is likely one of the major mechanisms through which it produces its sedative-hypnotic and anxiolytic actions.


 * Serotonin**

Ethanol also has significant effects o­n serotonin (5-HT), though it is not as well characterized as the afore mentioned o­nes. Ethanol has a biphasic effect o­n serotonin, first raising levels, then lowering them (48).

5-HT2 agonists, as well as serotonin reuptake inhibitors, have been found to substitute for ethanol in drug discrimination tests (49, 50). 5HT3 activity is probably responsible for the nausea with excessive consumption (51). It is also likely to partially account for increased dopamine release as antagonists have been shown to block ethanol induced dopamine release (52).

Ethanol administration eventually results in depressed 5-HT levels, and thus activity, due to increased peripheral metabolism of its precursor, l-tryptophan (53). Low levels of 5-HT are associated with increased aggression (53), and it is also quite likely that subsequent drinking episodes (and their accompanying initial increase in 5-HT levels) represent self-medication, to be followed by a fall in levels and repeat of the cycle. It seems possible that lowered 5-HT levels could contribute to the malaise of a next-day hangover, so the use of 50mg of 5-HTP upon waking might not be a bad idea.


 * Acetylcholine**

The cholinergic system is yet another target for the actions of ethanol (54). It has been found to act as a CO-agonist with acetylcholine at the nicotinic acetylcholine receptors, as well as to potentiate the effect of nicotine at this receptor, both of which ultimately results in an increase in mesolimbic dopamine (55). This interaction accounts quite nicely for the fact that 90% of ethanol addicts are also nicotine addicts (56).


 * Cannabinoid**

There is also likely some interaction by ethanol with the endocannabinoid system. They are somewhat similar in their effects in that both produce euphoria and stimulation at low doses and CNS depression at high doses (57). Cross-tolerance between the effects of THC and ethanol have been shown in rats (58), and down regulation of the CB1 subtype of cannabinoid receptors has been reported in rats chronically exposed to ethanol (59).

N-arichidonyl-ethanolamide (AnNH) is a naturally occurring derivative of the long-chain fatty acid, arachidonic acid, which has been found to bind to the CB1 cannabinoid receptor and to mimic the effects of THC (60). Ethanol increases the formation of AnNH from arachidonic acid.

The administration of a CB1 antagonist has been shown to limit ethanol consumption, suggesting that it might be involved in ethanol's reinforcement (62).


 * Catecholamines**

Ethanol consumption increases central and peripheral levels of epinephrine (E) and norepinephrine (NE), which contributes to the stimulatory affects of ethanol, particularly in the ascending arm of the blood alcohol curve (63, 64). Brain levels of norepinephrine have been shown to increase up to three-fold (64). These elevations occur primarily due to increased release and decreased clearance, rather than increases in synthesis (65). A consequence of this is eventual depletion of E and NE stores -- to as low as 8% and 20% in the adrenals after 4 days of ethanol intoxication (66). This fall likely contributes to the CNS depression that occurs with prolonged drinking.


 * Aggression**

There exists a real and significant relationship between ethanol and aggression (67), which might be of particular importance to bodybuilders who are supplementing with exogenous androgens or an EC stack, reading T-Mag o­n a regular basis, or any other things which could already be facilitating aggressive behavior.

The possible mechanisms by which it does this are several. As an anxiolytic, it can reduce fear of retaliation and consequences of behaviors, as a psychomotor stimulant, it can increase sensation-seeking behavior, and as an analgesic, it can reduce the perception of consequences of painful stimuli (68).

Another interesting possibility, is that ethanol disrupts executive cognitive functioning (ECF) (68). ECF encompasses higher order mental abilities such as abstract reasoning, attention, planning, self-monitoring, and the ability to adapt future behavior based o­n feedback from the outside world - basically ECF is the ability to use the above to consciously self-regulate goal directed behavior (69).

ECF is governed by the prefrontal cortex (70), and patients with lesions in this area have been noted to have decreased regulation of social behavior, including a "disinhibition syndrome" characterized by impulsivity, socially inappropriate behavior, and aggression (71, 72) - sound at all familiar? Lower scores o­n tests of ECF processes, such as the ability to inhibit aggression to obtain a monetary reward, have been reported for both prefrontal cortex lesioned patients and those intoxicated with ethanol (73). It should also be noted that it is o­n the ascending limb of the blood ethanol curve - i.e. when blood ethanol levels are increasing - when effects o­n ECF are particularly apparent (68).

The neurotransmitter, serotonin, has been implicated in this ethanol induced aggression as well. Decreases in serotonin levels, as well as 5-HT receptors, have been correlated with aggressive behavior (53). Acute ethanol consumption decreases the availability of the 5-HT precursor l-tryptophan to the brain (53). So, it might not be a bad idea to take 25-50mg of 5-HTP if you are prone to aggressive behavior when drinking.


 * Neurotoxicity**

Alcohol is neuorotoxic, and this toxicity is likely mediated by several factors. Fatty acid ethyl esters are a toxic byproduct of fatty acids and ethanol (74) which increase mitochondrial uncoupling and disrupt lipids of cell membranes (75) -- both l-carnitine and acetyl-l-carnitine in doses of 50mg/kg have been shown to decrease formation of FAEE by 3 to 6 fold, with ALC being particularly effective (75).

There is also strong evidence that ethanol induces oxidative damage -- in the form of increases free-radicals and indirect markers of oxidative damage such as lipid peroxides and protein carbonyl (76), thus the use of antioxidants is recommended -- Grape seed extract, resveratrol, SAMe, ALC, vitamin E, and selenium have all been shown effective (77, 78, 79, 80). As mentioned previously, NMDA modulated excitotoxicity is another mechanism.

Hepatotoxicity will not be reviewed as it is not a real concern for non-alcoholics, and alcoholics are not the intended audience of this article. Though, I will note that the notion that a single episode of concomitant Tylenol and ethanol use causing permanent liver damage has no basis in fact (81).


 * Memory**

The NMDA receptor complex is implicated in memory loss and blackouts from ethanol. This is due to its suppression of long-term potentiation (LTP) in the hippocampus (35). LTP is a sustained increase in synaptic efficacy following brief intense stimulation of presynaptic inputs (82) - basically, it is a physiological change by which memories are formed.

NMDA activation is required for the induction, but not sustaining of LTP (83), and as mentioned, ethanol results in the blockade of NMDA receptor transmission. Indeed, ethanol has been directly shown to inhibit LTP in concentrations as low as 5mM (equivalent to 1-2 drinks) (84).

This effect is very much dose dependent (as well as exhibiting interindividual differences and tending to be related to rapidly rising blood ethanol levels) and exists as a continuum, with lower concentrations producing minor loss and concentrations between 50-100mM (20+ drinks) producing so-called "blackouts" (85).

Contrary to popular notion, the occurrence of more frequent blackouts is not a predictor of subsequent alcoholism (86). Blackouts and short-term memory deficits have been found to be related (87), so if you want to test whether your drunken friend will experience a blackout the next day, ask him about a conversation 5 minutes earlier, and if he does not remember it at all, you will know that he will.

GABA (88), dopamine (89), and serotonin (90)are also likely to be involved in ethanol induced memory disruption, though the data for both is scarce at present. With serotonin, this is likely due to decreased availability of tryptophan and has been shown to be reversible with an SSRI. Thus, 25-50mg of 5-HTP is again recommended.

With that out of the way, we can turn to the ways in which ethanol can affect our fat loss and muscle building efforts.

They are several.

And, they are not good.


 * Fat Loss**

First, unlike most drugs, ethanol is nutritive -- and densely so. It contains 7.1 calories per gram (1) -- almost twice that of carbohydrates and protein. And, unlike the other nutrients, it does not appear to cause a significant amount of satiety (2). In other words, it typically does not replace calories, it adds to them.

Considering oÂ­ne drink (1 beer, 1 shot, 1 glass of wine) has about 12g of ethanol, this can add up in a hurry. I would not consider it unusual for a 200lb person to put down 20 drinks oÂ­n a good Friday night -- this is about 1600 calories just from the alcohol. That should put to rest the notion that beer makes you fat but hard liquor doesn't (though, the carbohydrates in beer would provide another 500-1000 calories depending oÂ­n if it were light or not). This is pretty much the entire day's calorie allowance for someone trying to lose bodyfat -- and I don't think I have to mention that we often follow this up with a 3 A.M. trip to a fast-food joint or all-you-can-eat buffet where we might get a couple thousand more.

There is some speculation in the literature that ethanol calories do not count, so we need to look at this notion. This idea primarily comes from the fact that epidemiological studies have shown that drinkers have lower Body Mass Indexes (BMI's) than their caloric intake would predict. In men, identical and even lower BMI's, despite calorie intakes several hundred higher than nondrinkers, and in women, it consistently LOWER BMI's despite higher calorie intakes than nondrinkers (3,4,5).

Most of these studies have not looked at actual body composition (3,4,5), thus weight differences could be explained by lower LBM levels -- and this would not be at all surprising considering some of ethanol's effects oÂ­n anabolic hormones which you will find out about later. In addition, both dietary intake and anthropometric measures have merely been self-reported by subjects and obtained by mail by the researchers (6), with the reported daily calorie intake representing oÂ­nly 60-70% of the population's average daily energy needs (7).

However, a more interesting study is oÂ­ne by Addolorato et al. which looked at not oÂ­nly BMI, but body composition (via DEXA) as well, in 34 alcoholics vs. 43 matched controls -- all male (8). The alcoholic group had lower bodyfat levels, but they had identical LBM. oÂ­ne possible explanation is that the alcoholic group had increased levels of extracellular water, as is known to occur in alcoholic cirrhosis (9) and more recently has been found to occur in alcoholics without liver disease (10). It should also be noted that these are chronic alcoholics who could have some metabolic abnormalities that do not pertain to us.

Another study found weight loss with isocaloric substitution of ethanol for carbohydrates as well as less than expected weight gains when ethanol was added to a maintenance diet (11). Though, this could be accounted for to some extent by differences in glycogen storage (unlike carbohydrate, alcohol is not stored as glycogen), as well as muscle (due to hormonal issues -- more oÂ­n this below).

There are also several studies suggesting that alcohol calories do indeed count. Nearly 100 years ago, Atwater and Benedict conducted a series of 13 whole-body calorimetry experiments to test alcohol's nutritive value. They found that the difference in energy given off as heat when alcohol was consumed vs. when it was not was a mere 1% (12). Numerous studies looking at the short-term (less than 4 hours) thermogenic effect of alcohol all found less than 10% dissipation of alcohol energy (13) -- however, it appears that longer studies give a more accurate representation, so we will look at a couple of those.

1.32g/kg (10 drinks for a 200lb person) of alcohol given at meals resulted in a 7% increase in total energy expenditure over 24 hours -- equivalent to 25% of the total alcohol energy (14). Another study using a smaller amount of alcohol (.55g/kg) observed thermogenic dissipation equivalent to oÂ­nly 15% of the total alcohol energy (15).

Two other studies offer strong evidence that alcohol calories count. The first measured body weight and metabolic rate with isocaloric substitution of 75g of alcohol per day for two weeks, finding results identical to that of control (16). A 5 week study using both high (172g/day) and moderate (97g/day) alcohol substitution, along with control, found the fuel value of alcohol to be 95% and 99% of control, respectively, with the high and moderate intakes (17).

Now that we have seen some empirical studies, lets turn to the more basic physiology involved. Ethanol is well digested and absorbed, and losses through breath, sweat, and urine are negligible, so those can be ruled out (1).

At high concentration, the afore mentioned (part 1) Microsomal Ethanol Oxidizing System can come into play -- this results in oxidation of ethanol but with less efficient production of ATP vs. the ADH pathway (18). This hypothesis, however, cannot fully explain the claimed inefficiencies of alcohol metabolism, because the bulk of the energy produced from alcohol is in the final steps of its metabolism -- which is the same in both the MEOS and ADH pathways (3)

Another possibility is a futile cycle involving oxidation of alcohol to aldehyde followed by reduction back to alcohol (19). A few such cycles would completely eliminate net energy gain from alcohol, however, though there is some evidence for the existence of such cycles (20), there is no data oÂ­n its quantitative significance.

Also, as mentioned, ethanol stimulates catecholamine release which could enhance thermogenesis (21). Changes in physical activity is an uninvestigated possibility. There is also data to suggest an interaction between ethanol and leptin, though the consequences of this are yet to be elucidated.

On the other side of the coin, alcohol's metabolic byproduct, acetate, directly suppress fat oxidation (22), as opposed to carbohydrates, whose suppression is mediated by insulin. De novo lipogenesis from ethanol does occur, though it is less than 5% of the total calories -- the rest is oxidized to CO2 and H20 (23). However, as noted in part 1, this oxidation takes priority over fat and carbohydrate oxidation, so with a calorie surplus, it would be expected to result in a shift toward lipogenesis for these substrates.

So, while it should be clear that alcohol calories do indeed count, the notion that ethanol will magically cause fat gain is also mistaken. Basically, as always, it comes down to total caloric intake vs. caloric expenditure -- and ethanol will add about 85 calories per drink to intake, while increasing expenditure by an amount equal to about 15-25% of that value, depending oÂ­n amount ingested.


 * Muscle Gains**

If the caloric content of ethanol has not convinced you that it is not the best thing for body composition, its effects on muscle building hopefully will. Ethanol has been consistently shown to result in sustained, significant decreases in testosterone and GH levels -- as well as to increase cortisol in many studies (Hopefully, and in depth analysis of the importance of these hormones on body composition is not necessary). In addition, it also directly inhibits protein synthesis.


 * Growth Hormone**

The deleterious effects of ethanol on humans and animals is consistent and well-established in both adults and adolescents, with decreases in GH levels, GH mRNA (24), as well as GH releasing factor mRNA levels (25). In adolescent rats, administration of 3g/kg of ethanol, which, due to the faster metabolism of rats produced blood alcohol levels equivalent to only about 4-6 drinks for humans, caused a massive drop in GH levels to just 4-7% of control by the 1.5 hour mark (26) -- Levels were still down 66-86% after 24 hours. In adult rats, the same 3g/kg caused total suppression of GH release, with 2g/kg causing significant but not total suppression (27).

In young adult male humans, 1.5mg/kg disrupted the nocturnal rhythm of GH secretion in all subjects, as well as decreasing overall release by 30% (28). 1g/kg almost completely inhibited the nocturnal rise in growth hormone levels, while a mere .5mg/kg resulted in levels 1/3 that of control (29). Inhibition of hepatic IGF-1 synthesis (30, 31), and the IGF-1/IGFBP-1 ratio (31, 32), a marker of IGF-1 bioavailability, have also been shown to be negatively effected by ethanol.


 * Cortisol**

Ethanol has been found to both directly, and indirectly -- via increases in ACTH (33), increase cortisol production. 1.75g/kg increased levels by 152% at 4 hours and was still significantly higher than control at 24 hours in adult males (34). In addition, consumption of ethanol along with exercise resulted in a 61% increase in cortisol over alcohol alone (35). A study of adolescents admitted to the hospital with acute alcohol intoxication showed ACTH and cortisol levels 10 and 1.6 times that of controls in females, and 5.9 and 1.4 times as high in males -- however, a general stress response much be considered as a possibility in these circumstances (36).

Other studies, however, have not found such effects (28, 37, 38). Thus, some researchers have concluded that any increases in cortisol are due to a stress response from nausea rather than a direct effect of ethanol (38, 39). And, indded, in one study, a subjects that vomited displayed cortisol levels 5 times as high as his baseline value (28).


 * Leptin**

Leptin secretion is signaled by glucose metabolism in the fat cell -- most likely via the hexosamine biosynthetic pathway (40). The metabolism of ethanol to acetate followed by oxidation does not directly contribute to hexosamine flux, thus they are likely very much empty calories in this regard. However, there are a few interesting studies linking leptin and ethanol.

Serum leptin concentrations were found to be elevated in active alcoholics versus controls and former alcoholics, suggesting that it might be increasing leptin levels (41). Prolactin is increased by ethanol and it has been found to increase leptin (42,43), thus providing a possible mechanism. Subsequent studies have found elevations in leptin to be associated with increases in cravings and consumption of ethanol (44, 45), indicating that it might be leptin modulating alcohol intake rather than the vice versa. The only study that looked at the effects of ethanol consumption on leptin, found a decrease in leptin (46), but this could be explained by the aforementioned differences in metabolic pathways between glucose and ethanol. There really is no other data, so conclusions on what is going on are pretty much impossible to draw, but this should be a very interesting area to watch in the future.


 * Testosterone**

Finally, we get to the good part -- or bad, if you like to hit the sauce with regularity. Acute ingestion of ethanol has been fairly consistently shown to significantly suppress testosterone production in both animals and humans, adults and adolescents. We will first look at the mechanisms involved, then turn to studies looking at actual testosterone levels.

Ethanol exerts its hypogonadic effects through several direct and indirect mechanisms. The primary mechanism is through direct suppression of leydig cell functions, either through a direct toxic effect (including reduction of LH receptors) (47,48), free radical activity -- selenium was found to ameliorate ethanol induced testosterone suppression (49), through reductions of 3beta-HSD (this is the enzyme that converts androstenediol to testosterone as well as DHEA to androstenedione) (50), 17beta-HSD (converts androstenedione to testosterone) (51), and 17,20 lysase (converts progesterone to androstenedione) (50), and through depletion of NADPH generating enzymes -- NADPH is a cofactor utilized in many steps of steroidogenesis (52), and ethanol administration has been shown to result in a decrease in the enzymes responsible for the generation of NADPH (53, 54).

Ethanol has also been shown to decrease LH releasing hormone at the hypothalamus (55), to decrease LH release at the pituitary (56), as well as to inhibit betaLH mRNA in vitro (57). This could be mediated by endogenous opiates as they are known to be increased by ethanol, and opiate antagonists have been shown to increase LH release as well as to block ethanol induced testosterone suppression at the testicular level (58).

Nitric oxide (NO) has also been implicated in this suppression (remember that next time you pop some Viagra or a tribulus product). While NO stimulates LH releasing hormone in the hypothalamus (59) and LH release in the pituitary (60), its overall effect oÂ­n testosterone is negative due to its effects at the gonadal level (61). Substances that increase NO levels have been shown to inhibit testosterone secretion (61), as well as possibly inhibiting steroidogenic enzymes (62). Concomitant use of L-NAME, L-NA, or 7Ni (nitric oxide synthase inhibitors) with ethanol completely prevented the fall in testosterone seen with 3g/kg ethanol (63,64).

Another interesting possibility is a mechanism involving a neural connection between the brain and the gonads via adrenergic receptors. It has been shown that direct injection of adrenergic agonists into the hypothalamus decreased testosterone production at the testes, without a change in LH levels (65). As we saw in part 1, ethanol is known to increase catecholamine levels in the CNS. And, indeed injection of both phentolamine (alpha adrenergic antagonist) and propranolol (beta antagonist) were found to partially overcome ethanol's suppressive effect oÂ­n HCG stimulated testosterone production (66).

Before you go out and get these drugs, remember that adrenergic stimulation, PERIPHERALLY, has a positive effect oÂ­n testosterone levels. However, if anyone knows of adrenergic antagonists that oÂ­nly act centrally, not peripherally, feel free to let us know.

Let's now turn to some studies that looked directly at testosterone levels following acute alcohol administration. In adult males, 1.3g/kg of ethanol (about 10 drinks for a 200 lb person), caused a significant decrease vs. basal levels at the 60 minute mark. Differences for the next two hours were not significant, though the researches did not utilize a control group, so the natural morning rise in testosterone could have masked any effects (38). 1.5g/kg lowered levels by an average of 23% over a 24 hour period (28). 1.75g/kg lowered levels by 27% and 16% at 12 and 24 hours, respectively (34). Adolescent males admitted to the hospital for alcohol intoxication were found to have 21% lower testosterone levels than controls (36).

A couple of studies have looked at alcohol and exercise. 1.5g/kg depressed testosterone by more than 20% by 1 hour and was still depressed by the same margin at hour 10 (37). Interestingly, when the same ethanol dose was preceded by an exercise session, the suppressive effect continued for 22 hours -- and when exercise was performed during a hangover, significant suppression (21-32%) vs. ethanol alone continued for 26 hours. Compared to control, both ethanol groups had significantly lower testosterone levels for 42 hours - this is almost 2 full days. A much smaller intake (.83g/kg) did not result in a significant decrease (35).

All of this is at what are fairly moderate doses. Let's take a look at binge drinking doses.

Probably for ethical reasons, doses equating to 20+ drinks have not been studied in humans, so we must settle for rat data, but considering the effects at lower doses seem quite similar, these studies are likely quite relevant -- and could actually underestimate the effect, since, as we mentioned, these doses resulted in much lower blood alcohol levels in rats than humans.

3g/kg caused massive suppression of testosterone (67). Between hours 1.5 and 96 (yes, 4 days later), testosterone was reduced between 50-75% and, even a full week later, it was still down 40%. By week two, it was finally back to control level. 3g/kg also reduced HCG stimulated testosterone secretion by 75% (66). In male macaque monkeys, 2.5 and 3.5g/kg reduced testosterone levels by 63 and 70%, respectively (68)

One study in adolescent rats found that testosterone levels doubled for the first 3 of weeks of ethanol ingestion (69) -- however, this was with an intake equal to 90 drinks per day for a 200 lb person. If anyone tries this, please report back with your results.

On the other hand, levels below 1g/kg seem to have no deleritous effects (35, 70).

Another interesting tidbit -- increased testosterone levels were found to correlate with decreased symptoms of withdrawal in alcoholics -- and the authors recommended supplemental testosterone as a possible treatment strategy (71). Wonder if a doctor would buy this??


 * Alcohol and Estrogen**

Chronic alcoholics, in addition to being hypogonadal, exhibit sign of overt feminization (72). There is some evidence to suggest that ethanol might also increase the aromatization of testosterone to estradiol. Consumption of .9 - 2.1g/kg of beer or wine significantly (P <0.05 to P< 0.001) increased estradiol levels in healthy adult humans (73). A study in rats found levels of estradiol increased by 60% (to go along with 55% lower test levels) - however, this was with the equivalent of about 13 drinks/day for 1-2 months (74).

In addition, alcohol administration has been shown to increase estrogen receptor density (75, 76) and to decrease levels of a estradiol binding protein (77, 78) -- as well as to lower androgen receptor numbers (76). However, this has primarily been found in conjunction with alcoholic liver disease, so its relevance to acute consumption in questionable.

Another possibility is the existence of phytoestrogens in alcoholic beverages. Hops, used as a flavoring agent and preservative in beer, contains several powerful phytoestrogens, including 8-prenylnaringenin, genistein, and daidzein (79, 80). And, congeners, which are found primarily in dark liquors such as bourbon and wines have been found to contain biochanin A, beta-sitosterol (72, 80)


 * Testosterone and Females**

Ethanol's effects oÂ­n the female bodybuilder, however, are not so bleak. Because female testosterone production occurs primarily outside the gonadal structures (81), ethanol's effect oÂ­n LH is not as relevant -- and its effects oÂ­n Leydig cells obviously are not at all relevant. In addition, ethanol is known to stimulate adrenal activity (82) -- 25% of female testosterone production is produced as an intermediate in the production of cortisol in the adrenals (81).

This results in INCREASED testosterone levels in women after ethanol consumption. As little as .4g/kg caused a significant increase in testosterone levels (83),and 1.2g/kg and 2g/kg caused increases of 25% and 54% respectively (84).

Interestingly, serum epitestosterone is not proportionally increased, nor are urinary levels, thus the testosterone to epitestosterone ratio (T:Ep) used in athletic drug screenings is skewed. The same study mentioned above resulted in a T:Ep ratio of around 4.5 compared to 1.5 before drinking. Individual increases ranged from 1.9 to 8.7 times baseline (84). Given that the testing cutoff is 6:1, it is easy to see that this could result in a false positive (or perhaps be used as a handy excuse for a true positive).


 * Protein Synthesis**

Both ethanol and its metabolic byproduct, aldehyde, have been shown to reduce protein synthesis in skeletal muscle (85, 86, 87, 88). To make matters worse, it is predominately Type II, fast-twitch fibers that are affected, with type IIB being hit the hardest (85, 86, 87). This is not a good thing for bodybuilders, and it is a very bad thing for athletes.

With acute administration of real-world doses (.8 - 2.0g/kg) of ethanol, reductions in protein synthesis of 20-30% have been seen within about oÂ­ne to two hours of administration, this is before the previously reviewed hormonal changes occur, indicating that alcohol is exerting a direct effect (85, 86, 88). Within 24 hours, decreases of as high as 63% have been shown to occur (86), which likely reflects the added contribution of negative hormonal changes.

The mechanism behind this is not fully characterized. Reduction in both mRNA (86) and translational efficiency (87) have been observed. The generation of free-radicals, which are known to be increased by ethanol (89, 90), could be involved (91). Low levels of selenium and alpha-tocopherol (vitamin E) are found in alcoholics with myopathy (muscle wasting) (92). However, there is also evidence that does not support this theory (93). Another possibility is direct ischemic damage (94).

Given alcohol's hormonal effects and its direct effects oÂ­n protein synthesis, if you are going to indulge in fairly heavy alcohol consumption, it would probably be a very good idea to utilize a topical prohormone formulation (or a short-acting injectable ester of the real thing) the evening of drinking and the next day in order to minimize the damage to your hard earned muscle.


 * Indirect Effects: Immune System**

Even moderate, acute ethanol consumption can significantly influence susceptibility to infections caused by viral and bacterial pathogens -- and alcohol is usually consumed in a social setting, where exposure to pathogens will be increased. Obviously, if oÂ­ne is sick, workouts will suffer. -- thus, this is important.

Both in vitro and in vivo administration of ethanol blunts inflammatory cytokine response to bacterial stimulation (95, 96). Monocyte production of IL-1, IL-6, and TNF-alpha are decreased (97) - leading to defective host defense against microbial infection (98). In addition, immunomodulatory cytokines such as IL-10 and TGF-beta as well as the prostaglandin PGE2, are increased (97), leading to a downregulation of production of antigen specific T-cells - increasing susceptibility to viral infections (99).


 * Sleep**

Though, it is a CNS depressant, and can thus facilitate the onset of sleep (100, 101), ethanol has negative effects on its quality. Of particular importance is REM sleep, which is the deepest stage of sleep, and is most important for mental and physical recovery. Ethanol reliably disrupts REM sleep, at doses as low as 2-3 drinks (102, 103, 104). It increases the time to induction of REM as well as total time spent in REM, due to decreases in the number of REM sleep episodes as well as a prolongation of the non-REM phase of the REM-nonREM cycles (102, 103). These effects are dose dependent, so the more you drink, the more it is affected (103).


 * Hangover**

The cause of ethanol induced hangover is not fully elucidated, however there are several mechanism likely to contribute. The formation of prostaglandins (PG) is increased by ethanol (105), and the use of aspirin like drugs before and during drinking has been shown to significantly reduce the severity of hangover (106). The use of linoleic and linolenic acid, which can both act as inhibitors of PG formation, also reduced the severity of hangover (107). Fish oils, which reduce cytokine formation might be useful as well.

Congeners -- byproducts of ethanol preparation which occur mainly in dark liquors and wine -- are also a likely culprit (108) -- and indeed in patients consuming 1.5g/kg of ethanol, 33% of those who consumed bourbon reported severe hangover vs. only 3% of those who consumed vodka (109). In other words, if you can't see through it, don't do it.

Ethanol inhibits anti-diuretic hormone, and hydration attenuates but does not fully relieve hangover symptoms (110). Aldehyde may be a factor as well -- the use of an herbal preparation called Liv.52 was found to decrease hangover symptoms vs. placebo, and indeed lower aldehyde levels were found (11). However, this study was done by the makers of the product, so its results could be viewed as questionable. Prophylactic use of vitamin b6 (400mg before, during, and after) was shown to reduce hangover symptoms by 50% (112). Other factors contributing to hangovers include lack of sleep, lack of food consumption, increased physical activity while intoxicated, and overall poor physical health (108).


 * Conclusion**

Health issues aside, it should be clear that the regular consumption of significant quantities of alcohol is absolutely detrimental to one's efforts to improve body composition. However, we all know its consumption is woven into the very fabric of our society, so most of us are not going to do away with it completely. We will have to be content with merely minimizing the negative consequences of its consumption. Other than the numerous specific recommendations that appear in the body of this article, the main general thing you can do is limit total consumption.

Bottoms up!

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 * References**