Acetaldehyde is hardly a
household word in America, yet it is one of the most common neurotoxins in the
lives of tens of millions of people. It is a simple substance its chemical
formula is CH3CHO yet acetaldehyde insidiously promotes damage to brain
structure and function through numerous pathways.
Sources of Acetaldehyde
There are four main routes that bring acetaldehyde (abbreviated here as
"AH") into the human brain. These are alcohol consumption, Candida
"the yeast syndrome," exhaust from cars and trucks, and cigarette
smoking.
Ethanol (more commonly known as
alcohol) is the chemical contained in beer, wine, liquor and liqueurs that
gets people drunk. These beverages serve as carriers to get ethanol into the
drinker's brain, promoting some degree of intoxication. Once in the body,
alcohol is broken down into carbon dioxide and water. However, this process
takes time and occurs in several steps. The first step occurs primarily in the
liver, although other organs such as the brain and kidney can also perform
this stage of alcohol detoxification to a slight extent. An enzyme called
"alcohol dehydrogenase" converts alcohol into AH. Then another
enzyme "aldehyde dehydrogenase" must break the AH down into acetate.
Acetate can then serve as a fuel in cellular energy production. (Acetate is a
form of acetic acid, the acid that makes vinegar sour.)
However, the conversion of AH
to acetate does not always occur quickly or smoothly and therein lies the
problem. Research over the last several decades has shown that alcoholics tend
to rapidly convert alcohol to AH, but then convert AH to acetate very slowly,
thus giving AH a chance to work its mischief in the body.1 And depending on a
person's genetics, nutritional status, and exposure to other chemicals such as
formaldehyde, which also utilize aldehyde dehydrogenase for their
detoxification, even non-alcoholics may have difficulty rapidly detoxifying
AH.
The second major route of AH
into the brain is through its production by a yeast called Candida albicans.
Candida is known to occur in the intestinal tract of virtually all humans to
some degree. When present only in small amounts, being kept in check by a
healthy immune system and the so-called "friendly flora," such as
Acidophilus and Bifidus bacteria, Candida is relatively harmless. Yet due to
the modern overuse of antibiotics, birth control pills, and cortisone/prednisone
drug therapy, as well as excessive stress (which naturally produces excess
cortisone in the body), sugar consumption and malnutrition, millions of
Americans now suffer from an excessive growth of Candida in their intestines
the so-called "yeast syndrome."2 Candida lives by fermenting sugars
to produce energy. Unfortunately for the humans who harbor large colonies of
Candida in their gut, the waste by-product of this sugar fermentation by
Candida is AH.3 Biochemical research has shown that this AH may combine with
red blood cells, proteins, enzymes, and other substances present in the gut or
gut lining, and thus travel through the bloodstream to reach more distant
parts of the body such as the brain.3 Research has also shown that AH can then
detach from the red blood cells or proteins it traveled with through the
bloodstream, thus enabling AH to damage cells far from the site of its
intestinal production by Candida.3
For those suffering from the
yeast syndrome, the ingestion of beer, wine, and liqueurs provides a
double-barreled dose of AH. Not only is the alcohol in these beverages turned
into AH, but the malt and grain in beer and the sugar in wine and liqueurs
provide excellent fuel for Candida to produce the energy it needs to live.2
More AH is the inevitable by-product of the yeast's sugar fermentation.
When oil, gasoline, diesel
fuel, and natural gas are burned, ending up in the air, AH is produced.4 Thus,
another major route of entry into the body for AH is through inhaling air
laden with vehicle and factory exhaust. People who spend hours commuting in
dense freeway traffic, professional drivers such as truck and taxi drivers in
urban areas, and even those who live or work in heavily trafficked areas or
near freeways or major streets are especially at risk for inhaling small but
significant chronic levels of AH.
AH is also produced through the
burning of tobacco.7 Thus, heavy cigarette smokers are also at risk of
inhaling AH through the inhaled smoke. And while the amounts of AH inhaled
through auto exhaust and cigarette smoke may be small compared to that from
alcohol, research shows that low-dose chronic AH exposure may still be
sufficient to gradually damage proteins, enzymes and other cellular structures
in the brain and other organs.21
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.5
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.
|
Below
is a range of possible nutrient levels that may offer protection to
those suffering from chronic AH toxicity.
|
| NUTRIENT |
AMOUNT/DAY |
| (divide
into 2-3 doses, take with meals) |
| Thiamin (B1) |
50-500
mg |
| Niacin or Niacinamide
(B3)* |
50-500
mg |
| Pantothenic Acid (B5)
(Pantethine) |
25-200
mg |
| Pyridoxine (B6) |
25-150
mg |
| N-Acetyl-Cysteine
(NAC) |
500-2000
mg |
| Ascorbate (C) |
500-3000
mg |
| Zinc (Monomethionine,
Ascorbate or Citrate) |
15-30 mg |
| Gamma Linolenic Acid (GLA)** |
120-480
mg |
| Lipoic Acid (Thioctic
Acid) |
50-200
mg |
| Silymarin (Milk
Thistle Extract, 70-80%) |
200-600
mg |
* Those
with known or suspected liver disease or gout should use this only
with their physician's permission. Also, those who find the
"hot flush" action of niacin too unpleasant should use the
niacinamide form of B3
** From Borage Seed Oil or Evening Primrose Seed Oil |
Acetaldehyde induces
deficiencies of niacin and NAD. Niacin (Vitamin B3) is present in the human
body primarily in its coenzyme form, NAD.1 NAD is involved in the majority of
steps in which sugar and fat are burned for energy in all cells.10 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.11 Zinc is also required along with NAD
to activate these two enzymes.12
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.13 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.11
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
that AH 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.14
Acetaldehyde induces a
deficiency of Pyridoxal-5-Phosphate (P5P). P5P is the major coenzyme necessary
to form virtually all major brain neurotransmitters.10 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.10 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 E1.15 P5P helps regulate magnesium entry into cells,16 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.17 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.1,18
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.15 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.,15 and
psychiatrist Julian Lieb,19 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.20 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.20 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!20 Successfully detoxifying alcoholics have been shown to excrete
especially high levels of these opiate-like chemicals in their urine.20 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.20 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.20
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!7 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 a long-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 B311 and zinc-activated,12 this
provides an obvious rationale for their protective use in chronic alcohol/AH
toxicity situations. Finally, because chronic high tissue levels of AH impair
the normal process of recycling the active form of B3 (NAD) for continual
re-use,1 it is obvious why normal dietary levels of B3 might be insufficient
to provide optimal brain B3 levels in chronic AH toxicity situations.
Highly recommended
source of nutrients and supplements.
How did we
qualify VRP?
References:
| 1. Cleary, J.P. The
NAD Deficiency Diseases. J Orthomolecular Med, 1986, 1:164-74. |
| 2. Galland, L.D.
Nutrition and Candida Albicans, 1986 A Year in Nutritional Medicine,
ed J. Bland. New Canaan:Keats Pub., 1986, 203-238. |
| 3. Truss, C.O.
Metabolic Abnormalities in Patients with Chronic Candidiasis: The
Acetaldehyde Hypothesis. J Orthomolecular Psychiatry, 1984,
13:66-93. |
| 4. Levine, S. and
Kidd, P. Antioxidant Adaptation, pp. 70-71. San Francisco:
Biocurrents Pub., 1986. |
| 5. Tsuboi, K.K. et al.
Acetaldehyde-Dependent Changes in Hemoglobin and Oxygen Affinity of
Human Erythrocytes. Hemoglobin, 1981, 5:241-50. |
| 6. Tuma, D.J. et al.
The Interaction of Acetaldehyde with Tubulin, in: Ann NY Acad Sci,
ed. E. Rubin, Vol. 492, 1987. |
| 7. Sprince, H., et al.
Protective Action of Ascorbic Acid and Sulfur Compounds against
Acetaldehyde Toxicity: Implications in Alcoholism and Smoking.
Agents and Actions, 1975, 5:164-73. |
| 8. Williams, R.R., et
al. Induced Thiamin (Vitamin B1) Deficiency in Man. Arch Int Med,
1942, 69:721-38. |
| 9. Dreyfus, P.M. and
Victor, M. Effects of Thiamine Deficiency on the Central Nervous
System. Am J Clin Nutr, 1971, 9:414-25. |
| 10. Kutsky, R.J.
Handbook of Vitamins, Minerals, and Hormones, 2nd ed, p. 284. NYC:
Van Nostrand Reinhold, 1981. |
| 11. Lehninger, A.L.
Principles of Biochemistry, p. 761. NYC: Worth Pub., 1982. |
| 12. Das, I., et al.
Effects of Zinc Deficiency on Ethanol Metabolism and Alcohol and
Aldehyde Dehydrogenase Activities. J Lab Clin Med, 1984, 104:610-17. |
| 13. Lesser, M.
Nutrition and Vitamin Therapy, pp. 41-50. NYC: Bantam, 1981. |
| 14. Pike, R.L. and
Brown, M.L. Nutrition, An Integrated Approach, 3rd ed., pp 624. NYC:
Macmillian Pub., 1984. |
| 15. Horrobin, D.F. The
Importance of Gamma-Linolenic Acid and Prostaglandin E1 in Human
Nutrition and Medicine. J Holistic Med, 1981, 3:118-39. |
| 16. Abraham, G.E., et
al. Effect of Vitamin B6 on Plasma and Red Blood Cell Magnesium
Levels in Premenopausal Woman. Ann Clin Lab Sci, 1981, 11:333-36. |
| 17. Hoffer, A.
Orthomolecular Medicine for Physicians, p. 34. New Canaan: Keats
Pub, 1989. |
| 18. Lumeng, L. The
Role of Acetaldehyde in Mediating the Deleterious Effect of Ethanol
on Pyridoxal-5-Phosphate Metabolism. J Clin Invest, 1978, 62:286-93. |
| 19. Lieb, J. Elevated
Levels of Prostaglandin E2 and Thromboxane B2 in Depression. Prost
Leukotr Med, 1983, 10:361-67. |
| 20. Blum, K. and
Payne, J. Alcohol and the Addictive Brain, pp. 99- 216. NYC: The
Free Press, 1991. |
| 21. Sorrell, M.F. and
Tuma, D.J. The Functional Implications of Acetaldehyde Binding to
Cell Constituents; Ann NY Acad Sci, ed. E. Rubin, 1987, Vol. 492. |
| 22. Cleary, J.P.
Etiology and Biological Treatment of Alcohol Addiction. J Neurol
Orthop Med Surg, 1985, 6:75-77. |
