Originally Posted by CavefishPart 2
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.
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 one 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 on 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 on 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 on 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 only 60-70% of the population's average daily energy needs (7).
However, a more interesting study is one by Addolorato et al. which looked at not only 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. one 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 on 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 only 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 on 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 on amount ingested.
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.
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.
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 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.
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 on 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 on HCG stimulated testosterone production (66).
Before you go out and get these drugs, remember that adrenergic stimulation, PERIPHERALLY, has a positive effect on testosterone levels. However, if anyone knows of adrenergic antagonists that only 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 on the female bodybuilder, however, are not so bleak. Because female testosterone production occurs primarily outside the gonadal structures (81), ethanol's effect oÃƒâ€šÃ‚*n LH is not as relevant -- and its effects on 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).
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 one 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 on 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 one 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).
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).
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).
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.