Ways Alcohol Hinders Fat Loss

5 Ways Alcohol Hinders Fat Loss!

Many people enjoy alcohol’s sedating influence and use it as part of our society’s traditions. Here I’ve put together details about alcohol and will explain main concerns, how it is processed, what they contain, and more… Get the facts!

5 Ways Alcohol Hinders Fat Loss!

Alcohol use—as a well-established part of human culture—is something that has become almost as acceptable as eating and breathing. As a social facilitator and feel good drug of choice for many, alcohol is very popular indeed, with consumption at mass levels.

However, alcohols well-documented deleterious effects—diminished performance, mental impairment, possible addiction, diabetes and liver disease to varying degrees in certain individuals—could be seen as a good reason to steer clear of it.

This being said, many people enjoy its sedating influence and it does play a vital role in many of society’s traditions and practices. One effect alcohol has, which is not widely discussed, is its impact on body composition. In its purest form, ethyl alcohol, which supplies seven calories per gram, alcohol provides energy, bumping up ones total energy balance whenever it is consumed.

Unlike macronutrients such as carbohydratesproteins and fats, alcohol supplies what nutritionists often refer to as empty calories: calories without nutrition. To make matters worse, it is the first fuel to be used when combined with carbohydrates, fats and proteins, postponing the fat-burning process and contributing to greater fat storage.

Here is what diet guru Robert C. Atkins says regarding alcohols affect on fat storage:

“Here’s the problem with all alcoholic beverages, and the reason I recommend refraining from alcohol consumption on the diet. Alcohol, whenever taken in, is the first fuel to burn. While that’s going on, your body will not burn fat. This does not stop the weight loss, it simply postpones it, since the alcohol does not store as glycogen, and you immediately go back into ketosis/lipolysis after the alcohol is used up.

If you must drink alcohol, wine is an acceptable addition to levels beyond the Induction diet. If wine does not suit your taste, straight liquor such as scotch, rye, vodka, and gin would be appropriate, as long as the mixer is sugarless; this means no juice, tonic water; or non-diet soda. Seltzer and diet soda are appropriate.”

Although Mr. Atkins suggestions are valid ones, especially as he is advocating the elimination of additional sugars along with the higher calorie beers, any form of alcohol can pose problems for those wanting to shed unwanted fat to look their best.

Main concerns are as follows:

1. Alcohol Supplies Almost Twice As Many Calories As Protein And Carbs

At seven calories per gram, alcohol supplies almost twice as many as protein and carbohydrates. In fact, alcohol has only two fewer calories than fat, which has nine per gram. It must also be remembered that the calories in alcohol lack the nutrients beneficial for a healthy metabolism and will therefore hasten fat storage.

The calories found in the average alcoholic drink are quite concentrated compared to many foods, and this actually causes one to inadvertently take in many more calories than would otherwise be consumed. Alcohol is quite deceptive in that it passes through the system rapidly, often before the drinker is aware of the number of drinks they have had.

Alcoholic drinks also contain calories from other sources, which add to overall caloric intake. Certain cocktails, for example, contain fats. Wine and beer both have high carbohydrate content. Although the affects these various calorie types have on the body are different—carbohydrates release insulin, which can hasten fat storage, while fats will be stored directly in the fat cells—the overall result is added body fat.

An example of how many calories can be easily consumed can be seen with a small glass of wine: a 5-ounce glass of wine will typically contain 110 calories, 91 of which come from the alcohol itself (13 grams), with the remaining five grams coming from carbohydrates.

Beer contains more carbohydrates (although many of the “Lite” beers have a carb content similar to a glass of wine) and less alcohol than wine, but is seen as being more fattening, due to its higher energy content.

2. Alcohol Loosens The Inhibitions

While drinking, people usually will not stop to consider the impact alcohol is having on their bodies; such is alcohol’s affect on loosening the inhibitions. The result of this relaxed thinking could mean more calories consumed and extra body fat gains. Those drinking might also eat more of the wrong kinds of food, without thinking of the consequences.

null

Those drinking might also eat more of the wrong kinds of food, without thinking of the consequences.

Alcohol tends to have an appetite stimulating effect as it provides little in the way of nutrition, leaving a craving for other foods at the time of consumption. Add this to the fact that fatty and salty foods tend to accompany most occasions featuring alcohol (as well as alcohol actually stimulating one’s appetite for these kinds of foods), and the general loosening of resolve that goes with an inebriated mindset, and you have a recipe for excess fat gain. Alcohol has also been shown to affect motivation, making a healthy diet harder to stay on while it is being used.

3. Alcohol Can Damage The Stomach, Kidneys, And Liver

Given alcohol is a by-product of yeast digestion; it can have an irritating effect on the lining of the stomach and gradually weaken the kidneys and liver, leading to serious health problems—even death in certain instances. Any weakening of the stomach will lessen the rate and efficiency at which food is digested, which ultimately interferes with a healthy metabolism and the weight loss process.

The liver—which processes toxins and breaks down fats for fuel—is crucial when it comes to maintaining a healthy body composition. Alcohol is at its most destructive during the liver’s detoxification process.

4. Alcohol Lowers Testosterone

Testosterone, which has a powerful fat loss effect, is reduced whenever alcohol is consumed, thus halting its full potential as a fat burner. Also, testosterone as an anabolic hormone, contributes to gains in lean muscle mass. Lowered testosterone means fewer muscle gains, and less muscle means a lowered metabolic rate.

A lower metabolic rate will make the job of losing fat all the more harder. This is what governs the way we use energy. Those with a higher metabolic rate will burn more calories at rest. By interfering with testosterone production, alcohol indirectly causes the body to lower its metabolic rate (and thus the rate at which it uses energy) and directly prohibits testosterone from exerting its powerful fat-burning effects.

null

Lowered testosterone means fewer muscle gains, and less muscle means a lowered metabolic rate

5. Alcohol Increases Appetite

Touched on briefly in point two, alcohol can increase appetite, making the combination of alcohol and a fattening meal all the more worse. A Canadian study showed that alcohol consumed before a meal increased caloric intake to a far greater extent than did a carbohydrate drink. Also, researchers from Denmark’s Royal Veterinary and Agricultural University showed that if a group of men were given a meal and allowed to eat as much as they wanted, alcohol, rather than a soft drink, would increase the amount of food consumed.

How Is Alcohol Processed In The Body?

To gain an understanding of why alcohol affects us the way it does, it is important to known how it is processed in the body.

After consuming the first alcoholic drink, 25% of this alcohol is absorbed straight from the stomach into the bloodstream, with the remainder taken in through the small bowel. Alcohol is generally absorbed fairly rapidly, but its absorption can be quickened depending on several factors:

  1. The amount of food in the stomach (a fuller stomach slows the rate of absorption).
  2. Whether the drink is carbonated (champagne is absorbed more quickly than non-sparkling drinks).
  3. Alcohol concentration of the drink (higher alcohol drinks are absorbed faster).

Around 98% of alcohol that is consumed is processed in the liver, with the other two to ten percent being expelled through urine, breathing, or sweat. The amount of alcohol in a standard drink will take around 10 hours for the average person to process, which means the more that is consumed at any one point, the greater the rise in blood alcohol content. When the liver processes alcohol, it does so in one of two ways.

For the most part, alcohol is broken down by the enzyme alcohol dehydrogenase (ADH, which is contained in the liver cells). ADH then metabolizes the alcohol into acetaldehyde. Acetaldehyde is broken down into acetate by another enzyme, aldehyde dehydrogenase. In the final stage, the acetate is further metabolized to where it eventually exits the body as waste products carbon dioxide and water.

null

Around 98% of alcohol that is consumed is processed in the liver.

The other way alcohol can be processed is a less common alternative, which uses a different set of liver enzymes. This alternative pathway, called the microsomal ethanol-oxidizing system, is used when the blood has very high levels of alcohol.

Calorie And Nutrient Content Of Popular Alcohol Drinks

The alcohol content of our most popular beverages varies, so it is important to know exactly what percentage of alcohol is in any given drink if one is wanting to limit all the empty calories. The following percentages are usually contained in each standard drink—five ounces of wine, 12 ounces of beer or 1.5 ounces of 80 proof (40% alcohol) distilled liquor.

  • Beer: 5% alcohol
  • Wine: 12% alcohol
  • 100 proof liquor: 50% alcohol
  • 80 proof liquor: 40% alcohol

The caloric content and nutrient breakdown of several popular alcohol choices follows.

Beer

null

One Can Of Regular 4-5% Alcohol Beer Contains:

  • 14 milligrams of sodium (1%).
  • 12.6 grams of carbohydrates (4%).
  • 1.6 grams of protein.
  • 14.2 milligrams of calcium.
  • 96.1 grams of potassium.
  • Total Calories: 153 (includes 97 calories from alcohol).

One Can Of Low Alcohol (2.3% Alcohol) Beer Contains:

  • 34.7grams of carbohydrates (12%).
  • Total Calories: 139.

One Can Of Lite Beer Contains:

  • 14 milligrams of sodium.
  • 5.9 grams of carbohydrates.
  • 0.98 grams of proteins.
  • 14.4 milligrams of calcium.
  • 75.6 milligrams of potassium.
  • Total Calories: 105 (includes 78 calories from alcohol).

Wine

One Glass Of Champagne Contains:

  • 2 grams of carbohydrates.
  • Total Calories: 85 (includes 77 calories from alcohol).

One Glass Of Dessert Wine (Sweet) Contains:

  • 9 milligrams of sodium.
  • 14.1 grams of carbohydrates.
  • 0.1 milligrams of calcium.
  • 0.9 milligrams of potassium.
  • Total Calories: 165 (includes 110 calories from alcohol).

One Glass Of Reduced Alcohol (6%) Wine Contains:

  • 10 milligrams of sodium.
  • 13.3 milligrams of calcium.
  • 130.2 milligrams of potassium.
  • 1.7 grams of carbohydrate.
  • Total Calories: 74 (including 66 calories from alcohol).
null

One Glass Of Red Wine (Claret) Contains:

  • 4.4 grams of carbohydrate.
  • 0.1 grams of protein.
  • Total Calories: 123 (including 105 calories from alcohol).

One Glass Of Table Wine Contains:

  • 7 milligrams of sodium.
  • 4 grams of carbohydrate.
  • 0.1 grams of protein.
  • 11.8 milligrams of calcium.
  • 146.5 milligrams of potassium.
  • Total Calories: 124 (including 108 from alcohol)/

One Glass Of White Wine (Riesling, Chablis) Contains:

  • 5.5 grams of carbohydrate.
  • 0.1 grams of protein.
  • Total Calories: 120 (including 98 calories from alcohol).

One Glass Of White Sparkling Wine Contains:

  • 4 grams of carbohydrates (all of white are sugars).
  • Total Calories: 93 (including 77 calories from alcohol)

Liquors

One Ounce Of Gin (40% Alcohol) Contains:

  • 0.6 milligrams of potassium.
  • Total Calories: 64 from alcohol content.

One Ounce Of Rum (40% Alcohol) Contains:

  • 0.6 grams of potassium.
  • Total Calories: 64 from alcohol content.

One Ounce Of Vodka (40% Alcohol) Contains:

  • 0.6 milligrams of potassium.
  • Total Calories: 64 from alcohol content.

One Ounce Of Whiskey (40% Alcohol Contains):

  • 0.6 milligrams of potassium.
  • Total Calories: 64 from alcohol content.
null

Liqueurs

One Nip Of Baileys Irish Cream Contains:

  • 5.8 grams of fat (3.5 grams of this saturated fat).
  • 14 milligrams of cholesterol.
  • 33 milligrams of sodium.
  • 7.4 grams of carbohydrate.
  • 1.2 grams of protein.
  • Total Calories: 121 (including 35 from alcohol).
null

One Nip Of Ouzo (40% Alcohol) Contains:

  • 11 grams of carbohydrate (10.9 of this is sugar).
  • Total Calories: 103 (including 70 from alcohol).

One Nip Of Schnapps (40% Alcohol) Contains:

  • 7 grams of carbohydrate.
  • Total Calories: 100 (including 70 from alcohol).

One Nip Of Curacao (35% Alcohol) Contains:

  • 6 grams of carbohydrate.
  • Total Calories: 95 (including 56 from alcohol).

One Nip Of Amaretto (38% Alcohol) Contains:

  • 17 grams of carbohydrate.
  • Total Calories: 110 (including 42 from alcohol).

One Nip Of Coffee Liqueur Contains:

  • 3 milligrams of sodium.
  • 11.2 grams of carbohydrate (all sugars).
  • 0.3 milligrams of calcium.
  • 10.4 milligrams of potassium.
  • Total Calories: 107 (including 63 from alcohol).

What Are The Best Alcohol Choices

If you really have to drink, what are the best choices? Some lower calorie brands to hit the market are showing promise, as are some of the more traditional alternatives.

As shown above, total caloric content of various alcoholic drinks varies, with beer generally containing the highest number, considering the smaller amount of alcohol found in this drink compared with others. Various spirits (also known as liquor) generally contain around 64 calories per nip, but these do add up depending on the strength of the drink (for example, a double will contain two nips, or 128 calories).

Combine this with one glass of coke (around 180 calories, 95% of these from sugars) and your typical bourbon and coke could supply 308 calories—double the number found in the average can of beer. Wine generally contains around 100 to 125 calories per medium sized glass. It also contains more alcohol than beer given the same volume, making it a better choice calorie-wise, as less would be consumed at any one sitting.

Liqueurs, although usually around 100 calories per nip, are often consumed with other, often-higher calorie mixers such as coke or milk to make cocktails, bumping the calorie content way up. Baileys Irish Creme, one of the highest calorie alcohols, contains 121 calories per nip, with a comparatively low alcohol content (17% compared to around 25-35 for most liqueurs). It is usually consumed 2-3 nips at a time given its lower alcohol strength. It is definitely one worth avoiding if weight loss is the aim.

null

Drink alcohol with a lower caloric value, and a higher alcohol percentage (like wine for example). Less will be consumed, meaning lower overall calorie consumption.

The worst alcohol choices would be the cream based drinks such as eggnog (340 calories without the alcohol) and an Amaretto Sour (includes tequila and orange juice and contains 421 calories). The highest calorie cocktail of the all would be the Vodka Mudslide, which contains coffee liqueur, Irish cream and vanilla ice cream and supplies 820 calories.

It would be better to drink a smaller quantity of liqueur with a healthier, lower calorie base such as trim milk or tomato juice (the latter being the base for a Bloody Mary cocktail).

Given alcohol taste is an individual matter, and people will usually choose what they like, rather than what they are advised to consume based on the health content of the drink, it is no easy task trying to persuade someone to change their drinking habits. The above information can however be used by one who is wanting to make some physical changes by lowering the overall caloric content of what they drink.

Some more general guidelines follow:

  1. Drink alcohol with a lower caloric value, and a higher alcohol percentage (like wine for example). Less will be consumed, meaning lower overall calorie consumption.
  2. Avoid high-calorie liqueurs. These are extremely deceptive (they taste so good) and will add enormously to overall caloric content.
  3. Keep healthy food on hand when drinking. As mentioned, drinking will relax the inhibitions and cause one to compromise their nutritional habits.
  4. If drinking beer, try a lower calorie alternative. Also, drink diet sodas with various spirits to significantly lower the calorie content of these drinks.
  5. Drink water between alcoholic drinks. This will increase feelings of fullness and may help to prevent over consumption of alcohol.

Conclusion

So what is one to do? Given alcohol plays a large role in celebration and social cohesion, can one completely refrain from its use? It really depends on the goals a person has. Most could probably consume moderate levels of alcohol (two or three standard drinks three to four times per week) without any problem.

Larger amounts (more than seven drinks at any one time), often described as binge drinking, can cause major problems and probably should not be advocated. Maintaining reasonable levels of health, while enjoying a few drinks—using moderation as the key—should be no problem. However, athletes—who definitely are not your average population—wanting to improve performance, and those wanting to lose weight are a different issue entirely.

Alcohol, as shown, will negate any efforts to lose body fat and will alter performance for the worst. The best advice would be to totally abstain until performance and weight loss goals are obtained.

Ray Audette, author of the NeanderThin Diet, provides sound advice for anyone wanting to lose weight while drinking alcohol. Remember, to be at your best physically you can’t have it both ways and Mr Audette provides a good rationale as to why.

“Don’t Drink Alcohol[.] It is best not to consume alcohol in any amount from any source. Alcohol is a by-product of yeast digestion (the yeast equivalent of urine) and is known to damage the stomach, kidneys, and liver. Alcohol adds fat principally by producing cravings for both it and other carbohydrates (see snack trays at any bar) and even other addictive substances (ask any former smoker.) It is almost impossible to drink alcohol and follow the hunter-gatherer lifestyle. If you must drink, do so only on special occasions (once or twice a year) and stick to alcohols derived from fruit (wine and champagne.)”

References
  1. Buemann, B., Toubro, S., & Astrup, A. (2002). The effect of wine or beer versus a carbonated soft drink, served at a meal, on ad libitum energy intake. International Journal of Obesity and Related Metabolic Disorders, 26, 1367-1372.
  2. Borushek, A. (2006). CalorieKing alcohol information. [Online]
  3. Shape Fit. (2006). How alcohol effects your weight loss—alcohol calories and fat. [Online]
  4. Tremblay, A., & St-Pierre, S. (1996). The hyperphagic effect of a high-fat diet and alcohol intake persists after control for energy density. American Journal of Clinical Nutrition, 63, 479-482.

Women are more affected by alcohol than men

Alcohol
ethanol

Alcohol in men vs women; women are….
more affected by alcohol than men

Why are women more affected by alcohol than men
1) they are smaller (less total body mass)
2) have less water to dilute alcohol (bc they are more % fat; lean muscle is 75% water, fat tissue is 15% water) per body weight
3) have less ADH in stomach lining (consumes 10% of ethanol vs 30% for men) making them more sensitive to alcohol

Nutrition of Alcohol
Yields 7kcal/gram

Alcohol damages what organs?
all organs in the body

In US for 18-24 year olds how many deaths/injuries are there?
>1,000 deaths and 500,000 injuries due to alcohol related accidents

What can hide alcoholic content?
caffeinated drinks

Binge Drinking
4 or more drinks for women and 5 or more drinks for men in 2 hrs

Result of binge drinking
can lead to acute alcohol intoxicaion and death

Absorption of Ethanol
1. Absorbed in stomach and small intestine => blood system
2. Food in stomach slows absorption
3. BAC increases

BAC of 0.08 means
0.08% alcohol in blood or 8×10^-4 g/mL blood

What does BAC depend on?
1. how many drinks you have
2. body size
3. gender
4. Time since ingestion

What BAC is driving impaired
.02%

Legal limit in CA
.08%

What do cells phones affect; does handheld or handsfree do this?
increase rate of injury crashes by 4 times; both handsfree and hand held

Pathways for alcohol metabolism
1. ADH pathway
2. MEOS pathway (Microsomal Ethanol Oxidizing System (MEOS) is an alternate pathway of ethanol metabolism that )

Metabolism (ADH Pathway) where does it occur?
1. Occurs in liver (70-90%)
2. Occurs in stomach (10-30%)
3. Occurs in cell cytosol; yields energy

Metabolism (ADH Pathway)
Ethanol => use alcohol dehydrogenase => acetylaldhyde => use aldehyde dehydrogenate => acetic acid => use CoA + Ac-CoA => TCA cycle => ATP => Fat via lipgenesis

What else gives rise to Acetyl-CoA?
1. Glucose => Fructose => acetyl-CoA
2. Glycolysis
3. FA oxidation
4. Ketogenic AA
5. Acetyl-CoA give rise to ketone bodies

2 Isoforms enzymes
1. ALDH1
2. ALDH2

ALDH1
cytosol high km (indication of protein activity)

ALDH2
mito low km
=> common mutation in East Asian Population => flushing and hangover
=> Drug target for alcoholics

Km is…
Km is the amount of substrate that produces the half of the maximum velocity of the enzyme.

MEOS pathway used when
1. When ADH can no longer be used, this is the second pathway for alcohol detoxification

How does MEOS work?
1. bypasses ADH
2. Uses NADPH, oxygen, and MEOS (Microsomal Ethanol Oxidizing System) to produce acetylaldehyde and NADP+ and water

MEOS includes
cytochrome P450 mono oxygenase (Cyt P450)

MEOS cytochrome P450 contains
heme group (Fe)

Equation for MEOS
RH + O2 + NADPH => ROH + H2O + NADP+

Why is MEOS important?
remove toxins (xenobiotics) and affect drug metabolism

What is alcohol’s effect on p450?
1. Alcohol competitively inhibits sedative detoxification
2. Acetaminophen => use p450 => liver toxin

Alcohol competitively inhibits sedative detoxification
Take a lot of sedative with alcohol can lead to death

Acetaminophen => use p450 => liver toxin
1. This process is stimulated/enhanced by alcohol
2. Increase cyt P450=> cause problems in body

Effects of alcohol
1. Alcohol interacts with endorphins receptors => increase dopamine
2. Alcohol depress CNS => decrease in respiration and heart rate
3. Alcohol can be addictive (esp. in US)
4. Alcohol intake can lead to tolerance => can increase consumption => can lead to dependence and addition

—————
Alcohol dehydrogenases (ADH) (EC 1.1.1.1) are a group of dehydrogenase enzymes that occur in many organisms and facilitate the interconversion between alcohols and aldehydes or ketones with the reduction of nicotinamide adenine dinucleotide (NAD+ to NADH). In humans and many other animals, they serve to break down alcohols that otherwise are toxic, and they also participate in generation of useful aldehyde, ketone, or alcohol groups during biosynthesis of various metabolites. In yeast, plants, and many bacteria, some alcohol dehydrogenases catalyze the opposite reaction as part of fermentation to ensure a constant supply of NAD+.
————–

Genetic evidence from comparisons of multiple organisms showed that a glutathione-dependent formaldehyde dehydrogenase, identical to a class III alcohol dehydrogenase (ADH-3/ADH5), is presumed to be the ancestral enzyme for the entire ADH family.[2][3][4] Early on in evolution, an effective method for eliminating both endogenous and exogenous formaldehyde was important and this capacity has conserved the ancestral ADH-3 through time. Gene duplication of ADH-3, followed by series of mutations, the other ADHs evolved.[3][4]

The ability to produce ethanol from sugar (which is the basis of how alcoholic beverages are made) is believed to have initially evolved in yeast. Though this feature is not adaptive from an energy point of view, by making alcohol in such high concentrations so that they would be toxic to other organisms, yeast cells could effectively eliminate their competition. Since rotting fruit can contain more than 4% of ethanol, animals eating the fruit needed a system to metabolize exogenous ethanol. This was thought to explain the conservation of ethanol active ADH in other species than yeast, though ADH-3 is now known to also have a major role in nitric oxide signaling.[5][6]

In humans, sequencing of the ADH1B gene (responsible for production of an alcohol dehydrogenase polypeptide) shows two variants, in which there is an SNP (single nucleotide polymorphism) that leads to either a Histidine or an Arginine residue in the enzyme catalyzing the conversion of ethanol into acetaldehyde. In the Histidine variant, the enzyme is much more effective at the aforementioned conversion.[7] The enzyme responsible for the conversion of acetaldehyde to acetate, however, remains unaffected, which leads to differential rates of substrate catalysis and causes a buildup of toxic acetaldehyde, causing cell damage.[7] In humans, various haplotypes arising from this mutation are more concentrated in regions near Eastern China, a region also known for its low alcohol tolerance and dependence.

A study was conducted in order to find a correlation between allelic distribution and alcoholism, and the results suggest that the allelic distribution arose along with rice cultivation in the region between 12,000 and 6,000 years ago.[8] In regions where rice was cultivated, rice was also fermented into ethanol.[8] The results of increased alcohol availability led to alcoholism and abuse by those able to acquire it, resulting in lower reproductive fitness.[8] Those with the variant allele have little tolerance for alcohol, thus lowering chance of dependence and abuse.[7][8] The hypothesis posits that those individuals with the His variant enzyme were sensitive enough to the effects of alcohol that differential reproductive success arose and the corresponding alleles were passed through the generations.

Classical Darwinian evolution would act to select against the detrimental form of the enzyme (Arg variant) because of the lowered reproductive success of individuals carrying the allele. The result would be a higher frequency of the allele responsible for the His-variant enzyme in regions that had been under selective pressure the longest. The distribution and frequency of the His variant follows the spread of rice cultivation to inland regions of Asia, with higher frequencies of the His variant in regions that have cultivated rice the longest.[7] The geographic distribution of the alleles seems to therefore be a result of natural selection against individuals with lower reproductive success, namely, those who carried the Arg variant allele and were more susceptible to alcoholism.[9]

———–

Mechanism of action in humans

Steps

  1. Binding of the coenzyme NAD+
  2. Binding of the alcohol substrate by coordination to zinc
  3. Deprotonation of His-51
  4. Deprotonation of nicotinamide ribose
  5. Deprotonation of Thr-48
  6. Deprotonation of the alcohol
  7. Hydride transfer from the alkoxide ion to NAD+, leading to NADH and a zinc bound aldehyde or ketone
  8. Release of the product aldehyde.

The mechanism in yeast and bacteria is the reverse of this reaction. These steps are supported through kinetic studies.[16]

Involved subunits

The substrate is coordinated to the zinc and this enzyme has two zinc atoms per subunit. One is the active site, which is involved in catalysis. In the active site, the ligands are Cys-46, Cys-174, His-67, and one water molecule. The other subunit is involved with structure. In this mechanism, the hydride from the alcohol goes to NAD+. Crystal structures indicate that the His-51 deprotonates the nicotinamide ribose, which deprotonates Ser-48. Finally, Ser-48 deprotonates the alcohol, making it an aldehyde.[16] From a mechanistic perspective, if the enzyme adds hydride to the re face of NAD+, the resulting hydrogen is incorporated into the pro-R position. Enzymes that add hydride to the re face are deemed Class A dehydrogenases.

Active site

The active site of alcohol dehydrogenase

The active site of human ADH1 (PDB:1HSO) consists of a zinc atom, His-67, Cys-174, Cys-46, Thr-48, His-51, Ile-269, Val-292, Ala-317, and Leu-319. In the commonly studied horse liver isoform, Thr-48 is a Ser, and Leu-319 is a Phe. The zinc coordinates the substrate (alcohol). The zinc is coordinated by Cys-46, Cys-174, and His-67. Leu-319, Ala-317, His-51, Ile-269 and Val-292 stabilize NAD+ by forming hydrogen bonds. His-51 and Ile-269 form hydrogen bonds with the alcohols on nicotinamide ribose. Phe-319, Ala-317 and Val-292 form hydrogen bonds with the amide on NAD+.[16]

Structural zinc site

The structural zinc binding motif in alcohol dehydrogenase from a MD simulation

Mammalian alcohol dehydrogenases also have a structural zinc site. This Zn ion plays a structural role and is crucial for protein stability. The structures of the catalytic and structural zinc sites in horse liver alcohol dehydrogenase (HLADH) as revealed in crystallographic structures, which has been studied computationally with quantum chemical as well as with classical molecular dynamics methods. The structural zinc site is composed of four closely spaced cysteine ligands (Cys97, Cys100, Cys103, and Cys111 in the amino acid sequence) positioned in an almost symmetric tetrahedron around the Zn ion. A recent study showed that the interaction between zinc and cysteine is governed by primarily an electrostatic contribution with an additional covalent contribution to the binding.[17]

Types

Human

In humans, ADH exists in multiple forms as a dimer and is encoded by at least seven different genes. There are five classes (I-V) of alcohol dehydrogenase, but the hepatic form that is used primarily in humans is class 1. Class 1 consists of α, β, and γ subunits that are encoded by the genes ADH1A, ADH1B, and ADH1C.[18] The enzyme is present at high levels in the liver and the lining of the stomach.[19] It catalyzes the oxidation of ethanol to acetaldehyde (ethanal):

CH3CH2OH + NAD+ → CH3CHO + NADH + H+

This allows the consumption of alcoholic beverages, but its evolutionary purpose is probably the breakdown of alcohols naturally contained in foods or produced by bacteria in the digestive tract.[20]

Another evolutionary purpose may be metabolism of the endogenous alcohol vitamin A (retinol), which generates the hormone retinoic acid, although the function here may be primarily the elimination of toxic levels of retinol.

Yeast and bacteria

Unlike humans, yeast and bacteria (except lactic acid bacteria, and E. coli in certain conditions) do not ferment glucose to lactate. Instead, they ferment it to ethanol and CO2. The overall reaction can be seen below:

Glucose + 2 ADP + 2 Pi → 2 ethanol + 2 CO2 + 2 ATP + 2 H2O[24]

Alcohol Dehydrogenase

In yeast[25] and many bacteria, alcohol dehydrogenase plays an important part in fermentation: Pyruvate resulting from glycolysis is converted to acetaldehyde and carbon dioxide, and the acetaldehyde is then reduced to ethanol by an alcohol dehydrogenase called ADH1. The purpose of this latter step is the regeneration of NAD+, so that the energy-generating glycolysis can continue. Humans exploit this process to produce alcoholic beverages, by letting yeast ferment various fruits or grains. It is interesting to note that yeast can produce and consume their own alcohol.

The main alcohol dehydrogenase in yeast is larger than the human one, consisting of four rather than just two subunits. It also contains zinc at its catalytic site. Together with the zinc-containing alcohol dehydrogenases of animals and humans, these enzymes from yeasts and many bacteria form the family of “long-chain”-alcohol dehydrogenases.

Brewer’s yeast also has another alcohol dehydrogenase, ADH2, which evolved out of a duplicate version of the chromosome containing the ADH1 gene. ADH2 is used by the yeast to convert ethanol back into acetaldehyde, and it is expressed only when sugar concentration is low. Having these two enzymes allows yeast to produce alcohol when sugar is plentiful (and this alcohol then kills off competing microbes), and then continue with the oxidation of the alcohol once the sugar, and competition, is gone.[26]

Plants[edit]

In plants, ADH catalyses the same reaction as in yeast and bacteria to ensure that there is a constant supply of NAD+. Maize has two versions of ADH – ADH1 and ADH2, Arabidopsis thaliana contains only one ADH gene. The structure of Arabidopsis ADH is 47%-conserved, relative to ADH from horse liver. Structurally and functionally important residues, such as the seven residues that provide ligands for the catalytic and noncatalytic zinc atoms, however, are conserved, suggesting that the enzymes have a similar structure.[27] ADH is constitutively expressed at low levels in the roots of young plants grown on agar. If the roots lack oxygen, the expression of ADH increases significantly.[28] Its expression is also increased in response to dehydration, to low temperatures, and to abscisic acid, and it plays an important role in fruit ripening, seedlings development, and pollen development.[29] Differences in the sequences of ADH in different species have been used to create phylogenies showing how closely related different species of plants are.[30] It is an ideal gene to use due to its convenient size (2–3 kb in length with a ~1000 nucleotide coding sequence) and low copy number.[29]

Iron-containing

Iron-containing alcohol dehydrogenase
PDB 1jqa EBI.jpg

bacillus stearothermophilus glycerol dehydrogenase complex with glycerol
Identifiers
Symbol Fe-ADH
Pfam PF00465
Pfam clan CL0224
InterPro IPR001670
PROSITE PDOC00059
SCOP 1jqa
SUPERFAMILY 1jqa

A third family of alcohol dehydrogenases, unrelated to the above two, are iron-containing ones. They occur in bacteria and fungi. In comparison to enzymes the above families, these enzymes are oxygen-sensitive.[citation needed] Members of the iron-containing alcohol dehydrogenase family include:

Moderate alcohol consumption linked to brain decline

By

beers in a bucket
The results of a new study have shown that even moderate alcohol intake can have a negative impact on cognitive health.
A new study concludes that even moderate alcohol consumption is linked to a raised risk of faster decline in brain health and mental function. The researchers say that their findings support the United Kingdom’s recent tightening of guidance on alcohol and question the limits given in the United States guidelines.

The study – by the University of Oxford and University College London, both in the U.K. – is published in the BMJ.

Alcohol consumption is a recognized global public health issue. According to the World Health Organization (WHO), “5.1 percent of the global burden of disease and injury is attributable to alcohol.”

In 2010, the World Health Assembly passed a resolution urging countries to “strengthen national responses to public health problems caused by the harmful use of alcohol.”

The U.K. government recently tightened their guidance on alcohol consumption, following new evidence of links to cancer.

They suggest that men and women “are safest not to drink regularly more than 14 units per week, to keep health risks from drinking alcohol to a low level.” This is roughly the amount of alcohol contained in 4 pints of strong beer or 5 large glasses of 14 percent wine.

However, the researchers behind the new study note that the U.S. guidelines allow a higher limit for men of 24.5 units per week.

‘Higher risk of hippocampal atrophy’

In their study paper, in which they discuss the rationale for their investigation, the researchers explain that a link between heavy drinking and adverse brain health – including dementia and degeneration of brain tissue – has already been well established.

However, fewer studies have examined the relationship between moderate drinking and brain health, and their evidence is largely inconsistent.

Therefore, the team decided to investigate whether or not there is a link between moderate alcohol consumption and brain changes by analyzing 30 years worth of data (collected between 1985 and 2015) on 550 healthy men and women who took part in the Whitehall II Study.

The participants were aged 43 on average when they started the study and none of them were alcohol dependent.

The data included information about weekly alcohol consumption and regular measures of brain function and mental performance. The participants also had an MRI brain scan at the end of the study.

When they analyzed the data, the researchers found that higher alcohol intake over the 30-year study period was tied to a higher risk of atrophy or tissue degeneration in the hippocampus, which is a part of the brain that is important for spatial orientation and memory.

They found that the link remained after taking into account factors that might influence it. These included sex, age, years of education, socioeconomic status, social and physical activity, medical history, smoking status, and stroke risk.

Moderate alcohol linked to three times greater risk of atrophy

However, while the participants whose alcohol intake exceeded 30 units per week had the highest risk of hippocampal atrophy (as expected), the analysis also showed a link to moderate alcohol consumption, which they defined as 14 to 21 units per week.

Compared with people who did not drink, people who drank moderately showed a three times higher risk of hippocampal atrophy.

The researchers also found that, compared with abstinence, light drinking – defined as no more than 7 units per week – offered no protective effect against hippocampal atrophy.

The brain scan data also showed evidence of greater deterioration in white matter with higher alcohol consumption. White matter integrity is important for mental ability.

Language fluency also declined faster with higher alcohol consumption. This is tested by asking people to give as many words starting with a particular letter as they can within the space of 1 minute.

However, decline in neither word recall nor semantic fluency was linked to higher alcohol consumption. Semantic fluency is tested by asking people to recall as many words in a particular category as they can within the space of 1 minute.

Questions idea that ‘normal’ drinking does no harm

While the study was not designed to show cause and effect, the results cannot be taken as proof that moderate drinking hastens brain decline. The authors suggest that further studies should now be done to confirm their findings.

Two strong points that could be argued as placing the study in the robust category are the amount of detailed data on potential influencing factors, and that alcohol consumption was measured regularly over a long period.

The authors suggest that their findings support the idea that alcohol might be a “modifiable risk factor for cognitive impairment, and primary prevention interventions targeted to later life could be too late.”

Because alcohol consumption affects a large proportion of the population, the implications for public health could be significant, they conclude.

In an editorial comment about the findings, Killian Welch, a consultant neuropsychiatrist from the Royal Edinburgh Hospital in the U.K., says that they support the “argument that drinking habits many regard as normal have adverse consequences for health.”

“With publication of this paper,” he adds, “justification of ‘moderate’ drinking on the grounds of brain health becomes a little harder.”

The authors of the study paper conclude:

Our findings support the recent reduction in U.K. safe limits and call into question the current U.S. guidelines, which suggest that up to 24.5 units a week is safe for men, as we found increased odds of hippocampal atrophy at just 14-21 units a week, and we found no support for a protective effect of light consumption on brain structure.”

What triggers your pain?

A 60 yr old woke up with leg pains. Her diet consists of meat and rice. She does not exercise but she works as a caregiver. I suggested some health tips for her that includes: whole foods diet with strong enzymes from fruits and veggies, dandelion tea or lemon grass, exercise and to apply and massage with oil mixed with essential oils of eucalyptus and other oils.

What aggravates or triggers your pain? What time of day do you feel the pain? What age did it start?

Please answer the following survey to identify the genes, environment,diet, behaviour, and other unknowns that trigger your pain.

Extra abdominal fat are three times more likely to develop memory loss and dementia

Your liver could be “eating” your brain, new research suggests.

People with extra abdominal fat are three times more likely than lean individuals to develop memory loss and dementia later in life, and now scientists say they may know why.

It seems that the liver and the hippocampus (the memory center in the brain), share a craving for a certain protein called PPARalpha. The liver uses PPARalpha to burn belly fat; the hippocampus uses PPARalpha to process memory.

In people with a large amount of belly fat, the liver needs to work overtime to metabolize the fat, and uses up all the PPARalpha — first depleting local stores and then raiding the rest of the body, including the brain, according to the new study. [10 Things You Didn’t Know About the Brain]

The process essentially starves the hippocampus of PPARalpha, thus hindering memory and learning, researchers at Rush University Medical Center in Chicago wrote in the study, published in the current edition of the journal Cell Reports.

Other news reports were incorrect in stating that the researchers established that obese individuals were 3.6 times more likely than lean individuals to develop dementia. That finding dates back to a 2008 study by researchers at the Kaiser Permanente Division of Research in Oakland, Calif.

In another study, described in a 2010 article in the Annals of Neurology, researchers at Boston University School of Medicine found that the greater the amount of belly fat, the greater the brain shrinkage in old age.

The surprising discovery in the new study is that the hippocampus uses PPARalpha to process memory and learning, and that this is a possible reason for the connection between belly fat and dementia and/or memory loss.

Rush University researchers, led by neurological sciences professor Kalipada Pahan, raised mice that were deficient in PPARalpha. Some mice had normal PPARalpha in the liver but depleted PPARalpha in the brain, and had poor memory and learning abilities. Others had normal PPARalpha in the brain but not the liver, and showed normal memory, as expected.

When the researchers injected PPARalpha into the hippocampus of PPARalpha-deficient mice, their learning and memory improved, Pahan said.

“Further research must be conducted to see how we could potentially maintain normal PPARalpha in the [human] brain in order to be resistant to memory loss,” Pahan told LiveScience.

PPARalpha thus provides a new avenue to explore in searching for a treatment or cure for Alzheimer’s disease, dementia, and related memory-loss and cognition problems, Pahan said.

Losing your belly fat won’t hurt, either.

Follow Christopher Wanjek

Ativan or Benzodiazepine oxidation is decreased in persons with liver disease

atiAlcohol withdrawal syndrome (AWS) may result in nausea, vomiting, diarrhea, weakness, sweating, tremors, tachycardia, hypertension, agitation, delirium, hallucinations, seizures, and death beginning 6 hours after alcohol cessation in alcoholics.

Benzodiazepines are cross-tolerant with ethanol and are considered first-line therapy for treating AWS.

Chlordiazepoxide and diazepam are first metabolized by hepatic oxidation, then glucuronidation.

Lorazepam and oxazepam undergo only hepatic glucuronidation.

Benzodiazepine oxidation is decreased in persons with liver disease and the elderly.

Accumulation with resultant excessive sedation and respiratory depression may be significant when administering chlordiazepoxide or diazepam to patients with impaired oxidative metabolism.

Lorazepam and oxazepam metabolism is minimally affected by age and liver disease. Chlordiazepoxide and diazepam are erratically absorbed by the intramuscular route. Lorazepam is predictably absorbed by the intramuscular route. Oxazepam is not available in parenteral form. Lorazepam appears to be the safest empiric choice among the various benzodiazepines for treating AWS in the elderly and in patients with liver disease, or those who require therapy by the intramuscular route.

https://www.ncbi.nlm.nih.gov/pubmed/8700792


Lorazepam, sold under the brand name Ativan among others, is a benzodiazepine medication.[2] It is used to treat anxiety disorders, trouble sleeping, active seizures including status epilepticus, alcohol withdrawal, and chemotherapy induced nausea and vomiting, as well as for surgery to interfere with memory formation and to sedate those who are being mechanically ventilated.[2][6] While it can be used for severe agitation, midazolam is usually preferred. It is also used, along with other treatments, for acute coronary syndrome due to cocaine use. It can be given by mouth or as an injection into a muscle or vein. When given by injection onset of effects is between one and thirty minutes and effects last for up to a day.[2]

Common side effects include weakness, sleepiness, low blood pressure, and a decreased effort to breathe. When given intravenously the person should be closely monitored. Among those who are depressed there may be an increased risk of suicide. With long-term use larger doses may be required for the same effect. Physical dependence and psychological dependence may also occur.

If stopped suddenly after long-term use, benzodiazepine withdrawal syndrome may occur. Older people more often develop adverse effects. In this age group lorazepam is associated with falls and hip fractures.

Due to these concerns, lorazepam use is generally only recommended for up to two to four weeks.[9]

Lorazepam was initially patented in 1963 and went on sale in the United States in 1977.[10] It is on the World Health Organization’s List of Essential Medicines, the most effective and safe medicines needed in a health system.[11] It is available as a generic medication.[2] The wholesale cost in the developing world of a typical dose by mouth is between US$0.02 and US$0.16 as of 2014.[12] In the United States as of 2015 a typical month supply is less than US$25.[13] In the United States in 2011, 28 million prescriptions for lorazepam were filled making it the second most prescribed benzodiazepine after alprazolam.

https://en.wikipedia.org/wiki/Lorazepam


Connie’s comments: Benzodiazepine should not be given to seniors who might have dementia and Alzheimer’s disease.

Can limited alcohol consumption help stave off age related cognitive impairment?

Summary: A new paper raised the question, can limited alcohol consumption help stave off age related cognitive impairment?

Source: PLOS.

Wisdom and grace come with age, but so do mental slowing and increased risk for dementia. As the elderly population continues to grow, preserving brain health to maintain independence and quality of life into older age is a pressing concern. Researchers have identified some unsurprising factors that reduce one’s risk for cognitive decline, including education, exercise or a healthy diet. But a more controversial question that continues to perplex scientists is whether alcohol consumption might also stave off cognitive impairment with age.

The aging brain on alcohol

Image shows a glass of wine.

Anyone who’s experienced the fatigue and brain fog that follow a night of heavy drinking doesn’t need science to explain the dangers of excessive alcohol intake. These health risks may be especially impactful to the older brain, which is already particularly vulnerable to environmental stressors. However, in moderation, a glass of wine or beer may not only be harmless, but may in fact also confer resilience to the aging brain against cognitive decline. Numerous studies have reported that moderate drinking is associated with lower rates of dementia, better cognitive performance, and slower decline in memory and executive functions. Yet, not all studies support the notion that a nightcap can help keep the brain sharp into late life. These discrepant findings raise two obvious questions. First, why are some patterns of drinking neurobiologically healthy, while others are toxic? And second, how can we better identify drinking behaviors that promote the healthiest trajectories of cognitive aging?

Neuroprotective in moderation, neurotoxic in excess

In excess, alcohol works as a neurotoxin on many levels. Studies in animals have shown that binging on ethanol kills neurons and impairs neurogenesis–the birth of new neurons–in the hippocampus, a region critical to creating new memories. Furthermore, alcohol-induced dementia results from brain damage that occurs with prolonged alcohol abuse. The reasons for the observed benefits of alcohol are less clear. In contrast to binge drinking, moderate alcohol intake increases neurogenesis and may help counteract oxidative stress in neurons. It’s well documented that what’s good for the heart is good for the brain, and indeed, vascular dysfunction often co-exists with or precipitates many forms of dementia. A prevailing theory is that the neuroprotective properties of drinking stem largely from their positive effects on cerebrovascular health. Alcohol can reduce risk for stroke and heart disease, lower blood pressure and increase HDL (“good”) cholesterol. However, some evidence that wine is more strongly neuroprotective than other forms of alcohol suggests that resveratrol, a potent antioxidant found in red wine, may also play a role. Although resveratrol minimizes dementia pathology in animals, the extremely high doses required make it unlikely to be the primary source of neuroprotection from alcohol.

Unraveling healthy drinking patterns for the aging brain

For our aging population to reap the greatest benefit from alcohol, it will be essential to determine patterns of healthy drinking that are optimized for the individual. This will require, foremost, a comprehensive understanding of how alcohol distinctly affects you versus me based on our genetics, sex or lifestyle. For example, alcohol has been found to differentially influence brain structure and risk for dementia or cognitive impairment for those with and without the apolipoprotein E4 gene, a strong risk factor for Alzheimer’s disease. Furthermore, studies have inconsistently reported sex differences in how drinking influences cognitive decline, which may be explained by differences in how men and women metabolize alcohol.

Despite overwhelming evidence that moderate alcohol intake can be healthy for the aging brain, there are striking incongruences across findings–which may be due to differences in study design or confounding factors­–that muddle our understanding of alcohol’s benefits. ‘Survival bias,’ in which healthier individuals participate in studies for longer, is an unavoidable complication in longitudinal studies of aging. This could significantly skew results if unhealthy drinkers drop out early, leaving only “healthy” drinkers to be studied in very old age. Furthermore, most human studies on alcohol and brain aging rely on observed associations, which can be replete with confounding factors. For instance, it’s known that drinkers tend to live more healthy lifestyles (e.g., they may exercise more or follow a Mediterranean diet), or may drink more often simply because they’re more socially active, which alone is known to be brain-healthy. What’s more, effects of alcohol on cognitive aging may depend on the type of alcohol consumed, how alcohol intake is measured, or the definition of “non-drinkers.” Many studies group life-long abstainers together with quitters, who may avoid alcohol due to poor health or may have developed health problems from alcohol abuse. However, my postdoctoral adviser Linda McEvoy, who studies effects of alcohol on brain aging at UC San Diego, explains that “Randomized controlled trials offer a better alternative to more definitely answer the question of how moderate alcohol intake affects cognitive function. Such trials have demonstrated beneficial cardiometabolic effects in those randomized to drink moderate amounts of alcohol.”

A prescription for alcohol?

Despite some uncertainties in the research so far, it appears that regular moderate drinking is unlikely to be hazardous to cognitive function and may even support healthy brain aging. Until we have further clarification, McEvoy offers some advice to those hoping to preserve brain health into late life: “If a person consumes alcohol, I would advise drinking moderate amounts of alcohol (one or two drinks) with dinner. If the person does not drink, I would not advise starting. Some individuals have a hard time controlling the amount they drink, and heavy drinking has detrimental effects on brain health and cognitive function.”