The bio-pathways of alcohol addiction

Acetaldehyde alters natural healthy brain neurotransmitter activity
It is becoming common knowledge that the true addictive substance of alcohol is not alcohol itself but the acetaldehyde (AH) produced when we metabolize it. If acetaldehyde is not efficiently broken down into acetate some of the excess drifts to the brain and combines with serotonin and / or dopamine to produce the infamous Tetrahydrolsoqulnoline (THIQ). THIQ is extremely addictive and in brain biochemistry actually fits the receptor sites that our natural pain killers (beta-endorphins) and "feel good" (serotonin) neurotransmitters are supposed to occupy. This causes a chain of very undesirable events. Our brain becomes incapable of receiving serotonin because our receptors sites are telling what little is there that they are full, very full with what it thinks is serotonin and beta-endorphin. The process is referred to as down-regulation. This condition is also why it takes more and more alcohol over time to get you "feeling right" once you've been at it a while. Because of the flood of THIQ in our brains our receptor sites begin to say "enough" and closes down beta-endorphin receptor sites.
Initially, when alcohol is introduced into your life, if you are sugar sensitive because of your genes or your dietary patterns have rendered you so, you most likely have a precondition of what is called up-regulation meaning that you have more beta-endorphin receptor sites than normal and you will overreact (in a potentially addictive way) to any morphine like drug- THIQ.
Also, we need to extract and metabolize various precursor amino acids from our food to make serotonin and other healthy neurotransmitters and heavy drinkers are often incapable of doing this because they suffer from malnutrition for a combination of reasons: they don't eat a sufficient amount of food; the types of diets they foster are naturally driven to are high simple carbs (body produces these cravings in an attempt to raise serotonin (especially when one quits drinking and THIQ is no longer fulfilling the receptor needs), and due to stomach and intestinal damage that alcohol does they are incapable of properly extracting and utilizing what little actual nutrition they might eat to produce healthy neurotransmitter activity.
Next month we will discuss in detail brain chemistry and alcohol consumption. For now let's take a close look at the evils of Acetaldehyde (excerpts from VRP's Nutritional News)

How Acetaldehyde Damages the Brain:

There are many ways that acetaldehyde (AH) can gradually damage brain structure and function through chronic, low-dose AH exposure. The following are some of them. Acetaldehyde alters red blood cell structure. It has been known since 1941 that AH easily combines with red blood cell membrane proteins to convert the red blood cells into a "time-release capsule" for AH, releasing the AH in the body far from the site where it attached to the red blood cell.3 As this happens, however, the membrane covering the red blood cell becomes stiffer.21 Yet in order to travel through the capillaries, which are the smallest blood vessels and which feed the trillions of individual cells, the red blood cell must be able to fold or deform. The average red blood cell diameter is 7 microns; yet a typical capillary is only 2 microns in diameter. Red blood cells stiffened through chronic AH exposure will have difficulty deforming sufficiently to pass through capillaries. Consequently, red blood cell-carried oxygen to many cells is reduced.3 (Our brains require 20% of all the oxygen we breathe!) In addition, the work of K.K. Tsuboi and colleagues has shown that AH forms stable combinations with hemoglobin in red blood cells. This reduces the ability of red blood cells to accept, hold, and transport oxygen through the bloodstream, which is their primary function.

Acetaldehyde decreases the ability of the protein tubulin to assemble into microtubules.6 Microtubules are long, thin, tube-like structures that serve several functions in the brain cell. They help provide structural support to the nerve cell, somewhat like girders in a bridge or a building, keeping the nerve cell and the dendrites semi-rigid. Dendrites are the feathery-looking extensions from the main body of the nerve cell which connect nerve cells to each other, with some neurons connecting through dendrites to as many as 100,000 other neurons. Microtubules also serve to transport nutrients and biochemical raw materials manufactured in the cell body to the dendrites. When this raw material transport is compromised, the dendrites will gradually atrophy and die off. Two classic examples of brain pathology involving degeneration of the dendrites in humans are chronic alcoholic brain damage and Alzheimer's disease.

Acetaldehyde induces a deficiency of vitamin B1. Thiamin, or Vitamin B1, is so critical to brain and nerve function it is often called the "nerve vitamin." AH has a very strong tendency to combine with B1, as the work of Herbert Sprince, M.D. (discussed below) has shown.7 Unfortunately, in detoxifying AH through combination with it, B1 is destroyed. Moderately severe B1 deficiency in humans leads to a group of symptoms called Wernicke-Korsakoff syndrome.9 This syndrome is characterized by mental confusion, poor memory, poor neuromuscular coordination, and visual disturbances. Its primary accepted cause is chronic alcoholism. B1 is also necessary for the production of ATP bioenergy in all body cells including the brain, and the brain must produce and use 20% of the body's energy total, even while asleep. Vitamin B1 is also essential for production of acetylcholine. Acetylcholine is one of the brain's major neurotransmitters, facilitating optimal memory, mental focus and concentration, and learning. Alzheimer's disease represents a rather extreme case of memory loss and impaired concentration due to destruction of acetylcholine-using brain cells. In a classic experiment reported in 1942, R.R. Williams and colleagues found that even mild B1 deficiency in humans continued over a long period of time (the experiment ran six months) produces symptoms including apathy, confusion, emotional instability, irritability, depression, feelings of impending doom, fatigue, insomnia, and headaches8 all symptoms of less-than-optimal brain function.

Acetaldehyde induces deficiencies of niacin and NAD. Niacin (Vitamin B3) is present in the human body primarily in its coenzyme form, NAD. NAD is involved in the majority of steps in which sugar and fat are burned for energy in all cells. NAD is normally the most plentiful vitamin coenzyme in the human brain. NAD is important as a catalyst in the production of many key, brain neurotransmitters, such as serotonin. Neurotransmitters are the biochemicals that allow nerve cells to communicate with each other. NAD is also the coenzyme that activates alcohol dehydrogenase and aldehyde dehydrogenase, the enzymes that break down alcohol and AH. Zinc is also required
along with NAD to activate these two enzymes. Since the need for NAD in all cells is great, yet the supply is limited, NAD is normally recycled continually during cellular energy production. Yet, when NAD helps detoxify AH, this recycling of NAD is blocked, and an altered form of NAD called "NADH" accumulates, impairing cellular biochemistry in many ways.1, 21 Thus, chronic AH exposure may produce a mild, functional, niacin/NAD deficiency, even in a person consuming a so-called "balanced diet" which meets RDA levels of niacin intake.

Extreme niacin deficiency produces the classic nutritional disease Pellegra with dramatic symptoms, both physical and mental. Since niacin is needed in large amounts for optimal brain function, a mild niacin deficiency tends to produce mostly psychological symptoms. These symptoms may include feeling fearful, apprehensive, suspicious, and worrying excessively with a gloomy, downcast, angry and depressed outlook. Headaches, insomnia, depression, agitation, and inability to concentrate may also occur. This profile certainly applies to many chronic alcoholics and Candida patients, who obviously suffer from long-term, mild AH exposure. Acetaldehyde reduces Acetyl Coenzyme A and impairs cellular energy production. Pantothenic Acid (Vitamin B5) is one of the most critical vitamins for normal brain function. The active form of B5 is Coenzyme A. Coenzyme A in turn is combined with acetate in all cells to form Acetyl Coenzyme A. Acetyl Coenzyme A is perhaps the most pivotal single biochemical in all cellular biochemistry; both sugar and fat must be transformed into Acetyl Coenzyme A to power the Krebs' cycle which produces 90% of all the energy used by every cell in the body, including brain cells. Unfortunately, for Acetyl Coenzyme A, however, AH has a strong affinity to combine with Acetyl Coenzyme A. The work of biochemist H.P. Ammon has shown thatAH suppresses the activity of Acetyl Coenzyme A in a dose-dependent fashion. He has also demonstrated that the energy-producing activity of cells falls in parallel with the declining levels of Acetyl Coenzyme A as the concentration of AH increases.1 The brain use. 20% of all body energy for normal function. Acetyl Coenzyme A is also necessary for the production of acetylcholine, the memory, learning and concentration neurotransmitter. Acetaldehyde induces a deficiency of Pyridoxal-5-Phosphate (P5P). P5P is the major coenzyme necessary to form virtually all major brain neurotransmitters. It is involved in all transamination reactions, whereby cells may convert many different amino acids into each other to satisfy their ever-shifting amino acid needs. P5P is necessary to convert essential fatty acids into their final use forms, as well as to turn linoleic acid into the key, nerve cell-regulating biochemical, Prostaglandin E1. P5P helps regulate magnesium entry into cells, and the level of excitability of nerve cells is strongly dependent upon their magnesium level. P5P is also necessary to convert vitamin B3, niacin/niacinamide, into the active coenzyme form, NAD. Unfortunately for P5P (and we humans who are so dependent on it), AH is known to strongly combine with the protein portion of P5P enzymes in a way that displaces the P5P portion of the molecule. This subjects P5P to an increased rate of destruction and results in abnormally low blood and tissue levels of this coenzyme.1, Acetaldehyde unfavorably influences prostaglandin metabolism. Delta-6-Desaturase is the enzyme that converts the common fatty acid linoleic acid into gamma linolenic acid, which is totally absent from any typical diet. Gamma linolenic acid in turn is the only raw material that can be converted into prostaglandin E1. Prostaglandin E1 is a key regulatory biochemical for both nerve cells and the immune system. It also serves to regulate the production of the pro-inflammatory prostaglandin E2. Prostaglandin E1 prevents excessive production of prostaglandin E2 from the dietary fatty acid, arachidonic acid, which is plentiful in meat, poultry and dairy products. Researchers in prostaglandin biochemistry have discovered, however, that AH is a powerful deactivator of Delta-6-Desaturase. AH thus tends to suppress gamma linolenic acid production, which in turn suppresses prostaglandin E1 production. Low prostaglandin E1 production "takes the brakes off" production of prostaglandin E2 and a related compound, TXB2, increasing their levels far above normal. The published research of David Horrobin, M.D., andpsychiatrist Julian Lieb, has shown high levels of prostaglandin E2 and TXB2, coupled with low levels of prostaglandin E1, to be a major causal factor in some forms of depression.

Acetaldehyde promotes addiction to toxic substances. Perhaps one of the most surprising ways AH may alter normal brain function is due to its tendency to combine in the brain with two key neurotransmitters, dopamine and serotonin. When AH and dopamine combine, they form a condensation product called salsolinol. When AH combines with serotonin, another product called beta-carboline is formed. Salsolinol and beta-carboline are two of a group of inter-related and interconvertible compounds called tetrahydro-isoquinolines. The various tetrahydro-isoquinolines which both animal and human research have shown to occur at high levels in the brains, spinal fluids, and urine of chronic alcoholics are closely related in structure, function, and addictive power to opiates! Successfully detoxifying alcoholics have been shown to excrete especially high levels of these opiate-like chemicals in their urine. Thus, these AH-generated, opiate-like biochemicals may at least partly explain why alcoholics are so addicted to alcohol, cigarette smokers to cigarettes, and Candida-sufferers to sugar, since all three of these conditions promote chronic excessive body AH levels. And, like opiates, these tetrahydroisoquinoline biochemicals would tend to promote lethargy, mental cloudiness and fogginess, depression, apathy, inability to concentrate, etc. These, of course, are symptoms common to both alcoholism and Candidiasis, the two conditions which would tend to generate the highest chronic AH levels in the body.

The difficulties discussed above that are caused by chronic AH toxicity should indicate to the reader that AH has a significant ability to compromise brain function. A partial summary of AH's damaging effects on brain function includes the following:
· Impaired memory
· Decreased ability to concentrate ("brain fog")
· Depression
· Slowed reflexes
· Lethargy and apathy
· Heightened irritability
· Decreased mental energy
· Increased anxiety and panic reactions
· Decreased sensory acuity
· Increased tendency to alcohol, sugar, and cigarette addiction
· Decreased sex drive
· Increased PMS and breast swelling/tenderness in women.

How Nutrition Can Help
Fortunately, applied nutrition science offers some protection against chronic AH toxicity, even when it is not possible to completely avoid the four main offenders that promote AH in our bodies alcohol, Candida, cigarettes, and heavy auto exhaust. Herbert Sprince, M.D. and his colleagues published many articles in the 1970's detailing the results of their experiments which used various nutrients to protect rats from AH poisoning. Sprince fed a control group of rats an amount of AH sufficient to kill 90% of the control group in 72 hours. The experimental group of rats given the same amount of AH were also given various nutrients, either singly or in combination, that might detoxify the AH. After 72 hours, the death rate for rats given large oral doses of Vitamin C was only 27% (vs 90% in controls), 20% for rats given the sulfur amino acid L-cysteine, 10% for rats receiving Vitamin B1, and an amazing 0% for rats protected by N-acetyl cysteine or lipoic acid. A lower dose combination of C, B1 and either L-Cysteine or N-acetyl cysteine also gave near 0% death rates! But, the nutrient doses Sprince administered were rather gigantic compared to RDA levels of nutrients, being equivalent to multi-gram doses for humans. Fortunately, however, most people are not subjected to such high levels of AH, so lower doses of these nutrients would doubtless provide significant AH-detoxifying power when used on along-term basis.

John Cleary, M.D. has published papers summarizing many doctors' and researchers' successful use of niacin (Vitamin B3) and zinc in alcohol and AH detoxification.1 Since the enzymes that break down alcohol and AH are both B3 and zinc-activated.

Hypoglycemia
If you are hypoglycemic or even borderline hypoglycemic it is very possible that it is difficult for you to "have just one". This is because the alcohol and sugar combined go right into your blood stream, causing a spike in insulin which drives your blood sugar down and that translates to that little voice that says "I need another drink". Combine that with the ravages of acetaldehyde toxicity and you're handcuffed to a need to self-medicate - more and more and more. Then add that to the compulsiveness that low-serotonin levels creates and you are battling the desire to self-medicate with some very mindless soldiers.
Hypoglycemic or sugar sensitive conditions can be inherited and they can be produced by long-term fast food, junk food diets - excessive sugar intake over time and yes, drinking alcohol.
This is the reason why AA is known for it's coffee urns, donuts and cigarettes. All of these help to raise blood sugar levels (which, for a short time, raise serotonin); and cigarettes are known to produce acetaldehyde as well!
When you consider that the body naturally produces about an ounce of alcohol a day from unused carbohydrates one can't help but think that in addition to the blood sugar rise sought, problem drinkers who try and quit without biochemically curing the addiction are possibly getting a little THIQ out of those junk food, coffee and cigarette diets as well!
Obviously diet is a huge concern for breaking the addiction to alcohol and for those who wish to moderate after they have healed the damage to their bodies. It is also a concern if one desires to enjoy their sobriety (or moderation) and hope for a long life. Studies show that the mortality rates even for long term ex drinkers is extremely high. This, I'm sure is due to the usual lack of addressing the damage and the other habits and bad diets pursued after they quit.
Markers for susceptibility for problem drinking are:
" You have the Concord of the alcohol dehydrogenase enzyme (a topic we will focus much on since altering the activity of this enzyme in a manner that would slow it's ability to produce acetaldehyde from the metabolizing of alcohol down actually makes us respond to alcohol differently).
" Your body is slow to detoxify (break down) acetaldehyde into acetate. If the studies regarding THIQ are true this is a very important topic to address regarding removing the desire to drink excessively and staying away from the propensity to become addicted (again). There are at least four other common sources of pollutants, which produce acetaldehyde in our bodies including smoking. It is very important to keep up the nutritional supplements that aggressively "clean up" acetaldehyde from the body.
" You are hypoglycemic or sugar sensitive and you self-medicate your low blood sugar symptoms with a drink(s). If you are sugar sensitive it is also likely that you will overreact to the THIQ floating around in your brain masked as beta-endorphin and absorb far more of both beta-endorphin and THIQ than the average bear.
In the next issue we will be breaking these topics down and discuss how diet and specific supplements can help to modify these conditions.


Therapeutic Supplements
This month's nutrient is vitamin B1 - Thiamine
Thiamine helps a great many bodily functions, acting as the coenzyme thiamine pyrophosphate (TPP). It has a key metabolic role in the cellular production of energy, mainly in glucose metabolism. Thiamine is also needed to metabolize ethanol, converting it to carbon dioxide and water. B1 helps in the initial steps of fatty acid and sterol production. In this way, thiamine also helps convert carbohydrate to fat for storage of potential energy.

Thiamine is important to the health of the nerves and nervous system, possibly because of its role in the synthesis of acetylcholine (via the production of acetyl CoA), an important neurotransmitter. With a lack of vitamin B1, the nerves are more sensitive to inflammation. Thiamine is linked to individual learning capacity and to growth in children. It is also important to the muscle tone of the stomach, intestines, and heart because of the function of acetylcholine at nerve synaptic junction. It is conceivable that adequate thiamine levels may help prevent the accumulation of fatty deposits in the arteries and thereby reduce the progression of atherosclerosis.

Thiamine is a water-soluble vitamin which is used to protect against excess water. This was the first identified B vitamin thus its name. It plays the role of a coenzyme in the Krebb's cycle (a biological pathway converting blood sugar (glucose) into energy) and the central nervous system needs vitamin B1 for functioning.

" Protects against acetaldehyde free radical damage. Very important!
" Free radical antioxidant - helps clean up acetaldehyde
" Was actually one of 3 components to Libby's patented alcohol withdrawal formula
" Helps relieve and heal alcoholic psychosis
" Helps in blood sugar management
" Heavy drinkers and those with liver disease have extreme deficiencies.

Thiamine is a vitamin essential to two entirely separate processes in humans: it is required for the oxygen-dependent part of the metabolism of carbohydrates (and alcohol) to produce energy and thiamine is also required for the membrane polarization /depolarization step in nerve transmission, (interestingly, the actual thiamine-dependent step is the same one blocked by the puffer fish nerve poison, tetrodotoxin.)
The effect of these two separate processes that both require thiamine means that alcohol consumption under conditions where the vitamin is limited, diverts available thiamine away from the brain to break down the alcohol. After this is exhausted, alcohol remaining is converted to fat, but in the interim, high levels of intermediate products of alcohol breakdown (prior to the thiamine-dependent step) float around in the blood and enter the brain. In order to dilute the alcohol and its breakdown products, water is drawn out of the tissues (including the brain) into the blood, dehydrating these tissues.
Clinical data indicates that 3mg thiamine per stubby of beer (375ml) is more than sufficient to prevent Wernicke-Korsakoff syndrome and around 90% of alcoholic brain damage, however hitherto unpublished findings of this researcher indicate that optimum hangover-eliminating doses are considerably larger.
This evidence would suggest that a third thiamine-dependent process may be a factor in hangovers. The most likely candidate appears to be a multienzyme complex called alpha-ketoglutarate dehydrogenase, which not only catalyses a critical thiamine-dependent step in the energy producing breakdown of alcohol, but is also at a point at which amino acid and carbohydrate metabolism interact. The substrate of this enzyme complex, alpha-ketoglutarate, can be converted to glutamate which in turn can be converted to gamma-aminobutyric acid, (GABA) an inhibitory neurotransmitter and the active metabolite of gamma-hydroxybutyrate, (GHB) with the street drug name "Fantasy".
It is because of this metabolic link that, while essential for normal brain function, glutamate is toxic in excess, (as anyone who has become ill after eating Chinese food with mono-sodium glutamate (MSG) can attest!)
Inhibition of alpha-ketoglutarate dehydrogenase under conditions of limited thiamine is likely to lead to a build-up of alpha-ketoglutarate formed from alcohol, which would be expected to drive the production of the alternative uninhibited glutamate pathway and hence to increase GABA production.

Absorption/Storage: Thiamine is absorbed in the upper and lower sections of the small intestine. Upon absorption, the vitamin is carried by the circulatory system to the liver, kidneys, and heart. Vitamin B1 may then combine with manganese resulting in an active enzyme that breaks down complex carbohydrates into simple sugars. Since this is a water-soluble vitamin it is not stored in the body; therefore, the excess is excreted in the urine. Thiamine must be replenished every 5-6 hours since it is excreted. Alcohol easily destroys this vitamin. Depletion of thiamine will result if sugar (alcohol) is consumed in excess and smoking has the same effect.

Healthy Sources:
Brazil nuts, brewer's yeast, buckwheat, millet, navy beans, oatmeal, peanuts with or without skins, pecans, pine nuts, pinto beans, pistachio nuts, rice polishings, red beans, soybean flour, dry soybeans, split peas, sunflower seeds, torula yeast, wheat bran and wheat germ.

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