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Indlæg: 27 aug 2006 16:55 
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Der er mange råd om at tage forskellige ting for at reducere skader fra stofferne, f.eks. at indtage 5-htp efter ecstasy. Til gengæld lurer der efterhånden flere og flere resultater fra videnskabens verden, som siger at enkelte substanser som anti-oxydanter taget ud af sammenhæng ikke har nær den virkning man troede.

Jeg tænkte at starte en tråd med et par artikler fra nettet som måske kunne give en almindelig ernæringsguide til folk. Forhåbentlig kommer der flere artikler til naturlige fødevarer med gavnlige virkninger.

Ofte er naturlige fødevarer også billigere end diverse præparater, og nemmere at få fat i (f.eks. kan 5-htp ikke købes i DK).


Senest rettet af Malkavian 27 aug 2006 17:06, rettet i alt 1 gang.

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Indlæg: 27 aug 2006 16:59 
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http://www.psychologytoday.com/articles ... 00012.html

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The cholesterol conundrum

Focuses on studies conducted by Jay Kaplan, Ph.D., which link cholesterol in the diet with the neurotransmitter serotonin and its manifestation in impulsive behavior. Highlights of the findings, which were reported in 'Psychosomatic Medicine' (Vol.56); Possible reasons why people on low-cholesterol diets die less often of heart disease, but more often of suicide, accidents, and homicide than the rest of the population; The National Cholesterol Education Program.


Why do people on low-cholesterol diets die somewhat less often of heartdisease, yet a lot more often of suicide, accidents, and homicide than the rest of the population?

Although the finding has cropped up in numerous studies over the past decade, it has met with much disbelief in medical circles. Nevertheless, an expert in heart disease research decided to test whether there might be any behavioral basis for the results. His studies link cholesterol in the diet with the neurotransmitter serotonin and its manifestation in impulsive behavior.

Jay Kaplan, Ph.D., looked at monkeys who were eating diets high in fat, but either low or high in cholesterol. After eight months, he found that the low-cholesterol monkeys, who had cholesterol readings of about 220, had no heart disease but were more hostile than the monkeys on a cheeseburger-like diet, whose levels hit 600.

"These monkeys went at it hammer and tong," says Kaplan, a professor of comparative medicine. "They engaged in more contact aggression--highly charged impulsive fighting--than the other monkeys."

Impulsivity, an increasingly scrutinized category of behavior, plays out in violence, suicide, and risk taking. And, impulsive people are likely to have a deficit of serotonin. "People in cholesterol-lowering trials might have been experiencing impulsivity, which led to the higher rates of suicide and accidents," suggests Kaplan.

He then measured serotonin levels in the monkeys' cerebrospinal fluid. Sure enough, the low-cholesterol, aggressive monkeys had less serotonin than the high-cholesterol monkeys.

Cholesterol is a major component of brain-cell membranes. Alterations in dietary cholesterol affect the fluidity and viscosity of the membranes, which house receptors for serotonin. So altering the condition of neuronal membranes may well alter the function of these serotonin receptors, explains Kaplan.

The findings, reported in Psycho-somatic Medicine (Vol. 56), raise questions about the National Cholesterol Education Program recommendations that Americans over the age of two significantly lower their intake of fat and cholesterol. "Can this diet do harm?" asks Kaplan. "For people who already have low serotonergic activity, a low-cholesterol diet might shove them across some threshold that makes them more likely to do things they might not otherwise do."

Or into depression. A recent study of men being treated for heart disease showed that those receiving cholesterol-lowering drugs experienced more symptoms of depression and anxiety than those who were not on the drugs.

Kaplan is swimming against a strong current. "The NIH," he laments, "has billions of dollars tied up in the [cholesterol] hypothesis."

Publication: Psychology Today
Publication Date: May/Jun 95
(Document ID: 1309)
---

Gode kilder til kolesterol er animalsk fedt og æg.


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Indlæg: 27 aug 2006 17:05 
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Teksten kun medtaget fra denne artikel. Se originalen for nogle informative grafikker:

http://www.whfoods.com/genpage.php?tnam ... t&dbid=103

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tryptophan
What can high-tryptophan foods do for you?

* Help regulate your appetite
* Help you sleep better
* Elevate your mood

What events can indicate a need for more high-tryptophan foods?

* Depression
* Anxiety
* Irritability
* Impatience
* Impulsiveness
* Inability to concentrate
* Weight gain or unexplained weight loss
* Slow growth in children
* Overeating and/or carbohydrate cravings
* Poor dream recall
* Insomnia

Food sources of tryptophan include red meat, dairy products, nuts, seeds, bananas, soybeans and soy products, tuna, shellfish, and turkey.

Description

What is tryptophan?

Tryptophan is one of the 10 essential amino acids that the body uses to synthesize the proteins it needs. It's well-known for its role in the production of nervous system messengers, especially those related to relaxation, restfulness, and sleep.

How it Functions

What is the function of tryptophan?
Preventing Niacin Deficiency

Tryptophan has two important functions. First, a small amount of the tryptophan we get in our diet (about 3%) is converted into niacin (vitamin B3) by the liver. This conversion can help prevent the symptoms associated with niacin deficiency when dietary intake of this vitamin is low.
Raising Serotonin Levels

Second, tryptophan serves as a precursor for serotonin, a neurotransmitter that helps the body regulate appetite, sleep patterns, and mood. Because of its ability to raise serotonin levels, tryptophan has been used therapeutically in the treatment of a variety of conditions, most notably insomnia, depression, and anxiety.

Deficiency Symptoms

What are deficiency symptoms for tryptophan?

As an essential amino acid, dietary deficiency of tryptophan may cause the symptoms characteristic of protein deficiency, which include weight loss and impaired growth in infants and children.

When accompanied by dietary niacin deficiency, lack of tryptophan in the diet may also cause pellagra, the classic niacin deficiency disease that is characterized by the "4 Ds" - dermatitis, diarrhea, dementia, and death. This condition is very rare in the United States, however, and cannot occur simply because of a tryptophan deficiency.

Dietary deficiency of tryptophan may lead to low levels of serotonin. Low serotonin levels are associated with depression, anxiety, irritability, impatience, impulsiveness, inability to concentrate, weight gain, overeating, carbohydrate cravings, poor dream recall, and insomnia.

Toxicity Symptoms

What are toxicity symptoms for tryptophan?

High dietary intake of tryptophan from food sources is not known to cause any symptoms of toxicity. In addition, tryptophan has been given therapeutically, as a prescription medicine or dietary supplement, in doses exceeding five grams per day with no report of adverse effects.

However, in 1989, the use of dietary supplements containing tryptophan was blamed for the development of a serious condition called eosinophilia-myalgia syndrome (EMS), which caused severe muscle and joint pain, high fever, weakness, swelling of the arms and legs, and shortness of breath in more than a thousand people. In addition, more than 30 deaths were attributed to EMS caused by tryptophan supplements.

Many experts believe that the EMS was caused by a contaminant that was found in one batch of tryptophan sold by one manufacturer and occurred in only a small number of susceptible individuals. However, the United States Food and Drug Administration, the agency responsible for overseeing the dietary supplement industry, remained convinced that high doses of tryptophan were categorically unsafe. Since 1989, tryptophan has not been available as a dietary supplement in the United States.

To date, a Tolerable Upper Intake Level (TUL) for tryptophan has not yet been established by the Institute of Medicine at the National Academy of Sciences.

Impact of Cooking, Storage and Processing

How do cooking, storage or processing affect tryptophan?

There is no research showing problematic effects of cooking, storage, or processing on tryptophan levels in food.

Factors that Affect Function

What factors might contribute to a deficiency of tryptophan?

Vitamin B6 is necessary for the conversion of tryptophan to both niacin and serotonin. Consequently, a dietary deficiency of vitamin B6 may result in low serotonin levels and/or impaired conversion of tryptophan to niacin.

In addition, several dietary, lifestyle, and health factors reduce the conversion of tryptophan to serotonin, including cigarette smoking, high sugar intake, alcohol abuse, excessive consumption of protein, hypoglycemia and diabetes.

Drug-Nutrient Interactions

What medications affect tryptophan?

People taking the anti-depressant medications known as selective serotonin reuptake inhibitors (SSRIs) (including Prozac, Paxil, and Zoloft) should consult a physician before taking any other supplement or medication that also increases the amount of, or the effect of, serotonin, in the body.

Nutrient Interactions

How do other nutrients interact with tryptophan?
Vitamin B6, vitamin C, folic acid and magnesium are necessary for the metabolization of tryptophan. In addition, tyrosine and phenylalanine compete with tryptophan for absorption.

Because of this, some healthcare practitioners believe that food sources of tryptophan do not cause a significant enough increase in blood levels of tryptophan to produce therapeutic results, and that tryptophan must, therefore, be taken as a supplement to increase its blood levels.

Health Conditions

What health conditions require special emphasis on tryptophan?

Tryptophan may play a role in the prevention and/or treatment of the following health conditions::

* Anxiety
* Depression
* Headaches
* Insomnia
* Nightmares
* Obesity
* Obsessive/compulsive disorder
* Pain
* Premenstrual syndrome
* Senile dementia
* Tourette's syndrome

Form in Dietary Supplements

What forms of tryptophan are found in dietary supplements?

Until 1989, tryptophan supplementation was standard practice in many countries around the world - including the United States - to treat insomnia, depression, and anxiety.

In the summer and fall of 1989, hundreds of people taking tryptophan supplements in the U.S. began to report the development of serious side effects including muscle and joint pain, high fever, weakness, swelling of the arms and legs, and shortness of breath, a constellation of symptoms that later became known as eosiniphilia-myalgia syndrome (EMS).

Upon investigation, it was discovered that nearly all of the cases of EMS could be traced back to a contaminant found in one batch of tryptophan produced by a Japanese manufacturer called Showa Denko K.K.

While all manufacturers of supplemental tryptophan synthesized this amino acid through a fementation process using bacteria, several months before the outbreak of EMS, Showa Denko K.K. had altered its process to make it more efficient and was apparently unaware that a toxic contaminant was being produced.

The United States Food and Drug Administration took immediate steps to limit the availability of tryptophan, and since 1989 this amino acid has not been sold as a dietary supplement. Tryptophan is still available, however, for use in the manufacture of infant formulas and entereral and parenteral (intravenous) nutritional supplements prescribed by physicians.

A few years ago, a new tryptophan-like supplement emerged in the U.S. marketplace. This supplement is called 5-hydroxytryptophan or 5-HTP. 5-HTP has been used in much the same way as tryptophan for the treatment of depression and insomnia, and for weight loss.

The reason is simple: the body ordinarily takes tryptophan and converts it into 5-HTP, and then takes the 5-HTP and converts it into serotonin. By taking 5-HTP, a person is taking a compound that is actually one step closer to serotonin than tryptophan.

Food Sources
Introduction to Nutrient Rating System Chart

The following chart shows the nutrients for which this food is either an excellent, very good or good source. Next to the nutrient name you will find the following information: the amount of the nutrient that is included in the noted serving of this food; the %Daily Value (DV) that that amount represents; the nutrient density rating; and the food's World's Healthiest Foods Rating. Underneath the chart is a table that summarizes how the ratings were devised. Read detailed information on our Nutrient Rating System.

Public Health Recommendations

What are current public health recommendations for tryptophan?

In its most recent 2005 public health recommendations for amino acids (published as the Dietary Reference Intakes for Energy, Carbohydrate, Fiber, Fat, Fatty Acids, Cholesterol, Protein, and Amino Acids (Macronutrients), National Academies Press, 2005), the National Academy of Sciences (NAS) established a general principle for tryptophan intake. The NAS recommended that all individuals 1 year of age or greater consume 7 milligrams of tryptophan for every 1 gram of food protein. Here is how that recommendation would look for each age and gender group, assuming RDA-level protein intake for each group:

* Children 1-3 years: 91 mg of tryptophan
* Children 4-8 years: 133 mg of tryptophan
* Males 9-13 years: 238 mg of tryptophan
* Males 14-18 years: 364 mg of tryptophan
* Males 19 years and older: 392 mg of tryptophan
* Females 9-13 years: 238 mg of tryptophan
* Females 14 years and older: 322 mg of tryptophan
* Pregnant or lactating females: 497 mg of tryptophan

References

* Bell C, Abrams J, Nutt D. Tryptophan depletion and its implications for psychiatry. Br J Psychiatry 2001 May;178:399-405.
* Celenza JL. Metabolism of tyrosine and tryptophan--new genes for old pathways. Curr Opin Plant Biol 2001 Jun;4(3):234-40.
* Crean J, Richards JB, and de Wit H. Effect of tryptophan depletion on impulsive behavior in men with or without a family history of alcoholism. Behav Brain Res 2002 Nov 15;136(2):349-57.
* Groff JL, Gropper SS, Hunt SM. Advanced Nutrition and Human Metabolism. West Publishing Company, New York, 1995.
* Lininger SW, et al. A-Z guide to drug-herb-vitamin interactions. Prima Health, Rocklin, CA, 2000.
* Mahan K, Escott-Stump S. Krause's Food, Nutrition, and Diet Therapy. WB Saunders Company; Philadelphia, 1996.
* Martinez A, Knappskog PM, Haavik J. A structural approach into human tryptophan hydroxylase and its implications for the regulation of serotonin biosynthesis. Curr Med Chem 2001 Jul;8(9):1077-91.
* Moore P, Landolt HP, Seifritz E, et al. Clinical and physiological consequences of rapid tryptophan depletion. Neuropsychopharmacology 2000 Dec;23(6):601-22.
* Van der Does AJ. The effects of tryptophan depletion on mood and psychiatric symptoms. J Affect Disord 2001 May;64(2-3):107-19.
* Widner B, Wirleitner B, Baier-Bitterlich G, et al. Cellular immune activation, neopterin production, tryptophan degradation and the development of immunodeficiency. Arch Immunol Ther Exp (Warsz) 2000;48(4):251-8.
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Indlæg: 27 aug 2006 19:08 
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Tilmeldt: 03 jun 2005 05:20
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Jeg ved ikke om du også tænkte på urtemedicin, men jeg kom lige til at tænke på det. Marietidslen er kendt for at være god for leveren og da man jo kan gro den slags selv, vil jeg mene det er relevant.

Marietidsel

Citat:
Indholdsstoffer: omfatter bitterstoffer, garvestoffer, kulhydrater, fed olie (højtumættede fedtsyrer), biogen amin (livsvigtigt proteinstof) og silymarin. Silymarin blev først opdaget i vor tid. Det består af 3 »flavandignaner« (plantefarvestoffer), nemlig silybin, silydianin og silychristin. Silymarin er et udpræget leverbeskyttende stof, der først og fremmest virker regenererende (fornyende) ved den i dag så udbredte fedtlever.

Ved sådanne skader og især ved deres forebyggelse, sætter virkningen af marietidsel ind og giver ikke alene beskyttelse, men hjælper også med til at helbrede uden, heller ikke ved høje doseringer, at være skadelig. Denne leverbeskyttende virkning blev entydigt påvist i dyreeksperimenter. Skadelige stoffer for leveren - f.eks. tetraklorkulstof, der fører til alvorlige necroser i leverparenkymet - blev standset. Stærkest blev dette påvist ved de alvorligste levergifte alfa-amanitin og falloidin fra knoldbladssvampen. Det lykkedes at reducere forsøgsdyrenes dødelighedsrate betydeligt. Samtidig blev det konstateret, at silymarin er helbredende over for de overordentlig alvorlige leverskader, der fremkaldes af falloidin. I dag anvender man silybinin (udvundet af silymarin) til at beskytte mennesker mod disse alvorlige forgiftninger. Kort sagt er marietidsel vigtig for lever og galdeblære.


Præcist hvor effektivt det er for at forhindre skader ved f.eks. heftig brug af alkohol ved jeg ikke, men man kunne forestille sig at det var en mulighed.


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Indlæg: 29 aug 2006 10:56 
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En måske vigtig advarsel for folk, der er på kolesterolsænkende medicin og som overvejer at tage stoffer, der påvirker serotonin systemet. Der er også noget interessant omkring alkohol, hvor de anbefaler at man tager 5-htp sammen med.

http://www.life-enhancement.com/article ... asp?ID=208

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Reducing Aggression and Violence
The Serotonin Connection
By Lane Lenard, Ph.D.

Robert Louis Stevenson's The Strange Case of Dr. Jekyll and Mr. Hyde has long been viewed as a dissection of the Good and Evil that can exist within a single human being. As the well-known story goes, Jekyll ingests his formula and is temporarily transformed from a conservative, well-respected English physician into a vain, uninhibited, terrifyingly violent criminal. Not only has Jekyll and Hyde stood the test of time as a morality tale, studies in brain chemistry and behavior more than a century later have shown Stevenson to have had remarkable prescience regarding the role of the neurotransmitter serotonin.

Of course, Jekyll's formula was simply a fictional plot device. Other than somehow releasing some of man's baser instincts, Stevenson could have had no idea what was actually going on neurochemically.

But the 100+ years of research on brain chemistry since Stevenson wrote his Victorian classic have revealed that anything that interferes with the actions of serotonin in the brain can bring about a syndrome that resembles Jekyll's transformation to Hyde. While certainly less dramatic than the transformation described by Stevenson, serotonin deficiency bears a striking resemblance in various manifestations as an increased tendency toward anxiety, depression, out-of-control disinhibition, and violence. Conversely, enhancing the activity of the serotonin system may have exactly the opposite effects in many people. Given our current knowledge of neurochemistry, there can be little doubt that if Stevenson were writing today, Jekyll's transforming formula would have been a potent anti-serotonergic agent.
Low levels of serotonin in the brain have
been associated with an increased
susceptibility to impulsive behavior,
aggression, overeating, depression,
alcohol abuse, and violent suicide.

Dr. Jekyll was initially trying to prove a philosophical point when he took this potion. It's hard to imagine anyone today knowingly taking such a potion, and yet, millions of people do things every day - many of them loudly and frequently endorsed by the general medical community, the Food and Drug Administration (FDA), and many other "experts" - that significantly reduce the brain's serotonergic function. The consequences of their behavior, including increased risk of depression, anxiety, alcoholism, suicide, and violent death, are only now coming to be recognized.

Among the best studied of these Jekyll-and-Hyde-like "potions" are the cholesterol-lowering drugs (e.g., Lopid, Questran, Lescol, Mevacor, Zocor, Pravachol) and the appetite-suppressors fenfluramine (the "fen" of fen-phen fame) and dexfenfluramine (the best-selling Redux). Fenfluramine (trade names, Pondimin and Ionamin) and Redux both act by depleting serotonin and may permanently destroy serotonergic neurons in the brain. Even weight-loss diets that are extremely low in fat have also been noted to cause Hyde-like behavior patterns in some people. Mortality associated with violence (suicides and injuries) has been observed to increase following the use of cholesterol-lowering drugs.1 In another study, patients with low cholesterol showed hypersensitivity to detecting anger and sadness in themselves.2 Apparently, these too result in reduced serotonin, although usually without the permanent damage caused by fenfluramine and Redux. Both of these drugs have recently been removed from the market, in part, because of their potent anti-serotonergic effects. (See Ephedra vs. Fen-Phen/Redux®).
Weight-loss diets that are extremely low
in fat have also been noted to cause
irritable and aggressive behavior patterns
in some people, probably because of the
way these diets can cause
serotonin suppression.

Serotonin, or 5-hydroxytryptamine (5-HT), was first isolated from blood exactly 50 years ago and was later identified as a neurotransmitter in the central nervous system (CNS). As a neurotransmitter, serotonin possesses a range of effects unmatched by any similar substance. Like its catecholamine cousins, adrenaline, noradrenaline, and dopamine, serotonin acts all over the body:3

* In the central nervous system (CNS), 5-HT has widespread and often profound implications, including a role in sleep, appetite, memory, learning, temperature regulation, mood, sexual behavior, cardiovascular function, muscle contraction, endocrine regulation, and, of course, depression.
* Low levels of serotonin in the brain have been associated with an increased susceptibility to impulsive behavior, aggression, overeating, depression, alcohol abuse, and violent suicide. Moreover, all these behaviors seem to be linked, so that the presence of one markedly increases the risk for any of the others.
* In the blood vessels, 5-HT constricts large arteries, thus helping to balance excessive dilation required for proper normal blood pressure control.
* In the intestines, 5-HT controls GI motility (movements of the stomach and intestinal musculature).
* In the periphery, 5-HT is a major factor in platelet homeostasis which could be of benefit in the treatment of diabetes.
* As Stevenson portrayed so well in Jekyll and Hyde, altering serotonergic activity may even be capable of inducing profound changes in personality. In his best-selling book, Listening to Prozac,4 psychiatrist Peter D. Kramer, M.D., has argued that taking Prozac - or similar agents that enhance serotonergic activity - may actually help some people reconfigure their personality. This has opened a broad new avenue of use by people with no obvious psychiatric illness, who just want to feel more confident, popular, mentally nimble, and emotionally resilient.

Nerve cells synthesize 5-HT by a two-step process that begins with the essential amino acid tryptophan, which must come from dietary sources. Once taken up into a nerve cell, tryptophan is converted into 5-hydroxytryptophan (5-HTP) with the help of the enzyme tryptophan hydroxylase (TPH). 5-HTP is converted in turn to 5-HT (serotonin). Studies show that taking supplements of tryptophan or 5-HTP will increase the amount of serotonin available for use by neurons.5 (Note: Chronic stress, with its concomitant increases in cortisol, can inhibit the conversion of dietary tryptophan to 5-HTP, but not 5-HTP to 5-HT. This suggests an advantage of using 5-HTP instead of tryptophan for relieving problems associated with stress.)

The first hints that serotonin played an important role in regulating aggressive behaviors came in the mid-1970s when researchers doing postmortem examinations on suicide victims noticed that these people had reduced levels of a major metabolite of serotonin called 5-hydroxyindoleacetic acid (5-HIAA) in their cerebrospinal fluid.6 Subsequent studies found lower levels of 5-HIAA in people who had attempted suicide, had severe depression, or had shown tendencies to harm themselves or others.7
Animals that have been selected for
domesticity (i.e., reduced aggression)
seem to have higher brain levels of
serotonin than their wild counterparts.

CROSS-SPECIES AGGRESSION CONTROL
Serotonin's influence over aggressive tendencies goes way back in the evolution of life. Studies over a wide range of species, from crustaceans to fish to lizards to hamsters to mice to dogs to nonhuman primates to human beings, have all demonstrated essentially the same results: reducing serotonergic activity leads to increases in aggressive behavior, and enhancing serotonergic function decreases aggressive behavior.7-13

This relationship can have some interesting ramifications. For example, animals that have been selected for domesticity (i.e., reduced aggression) may have higher brain levels of serotonin than their wild counterparts. Russian researchers studying silver foxes, for example, found that those selected for more than 30 years for tame behavior and no defensive reactions to humans had higher levels of both serotonin and 5-HIAA in various regions of the brain, compared with wild silver foxes bred in captivity. They also found higher levels of tryptophan hydroxylase (TPH, the primary enzyme involved in the production of serotonin) and lower levels of monoamine oxidase (MAO, the enzyme that removes serotonin from the synapse) in the domesticated animals.14

So sensitive is this serotonergic system that natural variations in serotonin levels among animals on a normal diet can affect their behavior in profound ways, possibly even spelling the difference between life and death. A team of researchers from the National Institute of Alcohol Abuse and Alcoholism (NIAAA) has been studying a colony of free-ranging rhesus monkeys living on a 475-acre sea island. Among their most important findings: those monkeys with the lowest CSF levels of 5-HIAA (indicating low serotonin) stand the greatest chance of getting injured and/or dying young.15
So sensitive is this serotonergic system
that natural variations in serotonin level
among animals on a normal diet can affect
their behavior in profound ways, possibly
even spelling the difference
between life and death.

The NIAAA researchers first took blood and CSF samples from 49 2-year-old male rhesus monkeys and then set them free on the island. Over the next 4 years, they closely and systematically observed the animals' behavior, paying particular attention to aggressive interactions. At the end of 4 years, six of the monkeys were dead, and five others were missing and presumed dead.

In retrospect, the animals' fate could have been predicted by their CSF 5-HIAA at age 2. Not a single monkey from the highest CSF 5-HIAA concentration quartile died or went missing. By contrast, 46% of the dead or missing came from the low end of the 5-HIAA concentration spectrum, with all but one coming from the two bottom quartiles.

The authors also observed that the monkeys that turned up dead or missing were the ones most likely to initiate or escalate aggressive encounters. Not surprisingly, these aggressive animals stood the greatest risk of suffering trauma or injury. Of the six animals whose death could be ascertained, four had died as a result of injuries sustained in a fight, and all four had had among the lowest levels of 5-HIAA at age 2.
A team of researchers has been studying
a colony of free-ranging rhesus monkeys
living on a 475-acre sea island. They have
found that those monkeys with the lowest
serotonin levels stand the greatest chance
of getting injured and/or dying young.

More subtle variations in social behavior have also been related to serotonin levels.16 Among 26 adolescent male rhesus monkeys from the same island colony, for example, those with the highest levels of CSF 5-HIAA concentration were seen spending more time grooming other group members and staying in close proximity to others. Those with the lowest levels of CSF 5-HIAA were more likely to leave their social groups at a younger age, an indication of lower social competence. Low CSF 5-HIAA animals were also observed to take greater physical risks, including longer leaps in the trees at greater heights. The authors suggested that this behavior indicated impaired impulse control.15

The drug parachlorophenylalanine (pCPA) inhibits serotonin synthesis, reducing the availability of serotonin in the brain. When pCPA is given to vervet monkeys, it makes them irritable and aggressive. When these same animals are then treated with the selective serotonin reuptake inhibitor (SSRI) Prozac or the serotonin precursor 5-hydroxytryptophan (5-HTP), both of which increase the availability of serotonin in brain synapses, there is no increase in aggressiveness.16

Since the body normally synthesizes serotonin from dietary tryptophan, altering the diet can also change behavior. For example, animals placed on a tryptophan-free diet, leading to reduced serotonin levels, have greater aggressive tendencies, especially during competitive social interactions like feeding.16
Monkeys with higher serotonin levels spent
more time grooming other group members
and stayed in close proximity to others.
In other words, they were more
social and affectionate.

When it comes to the need for serotonin, human beings appear to be no different than their cousins in the swamp. Feed us too little tryptophan and we can become impulsive, depressive, aggressive, and violent. Feed us enough tryptophan or 5-HTP and these traits diminish or disappear.

In one study, human subjects ingested an amino acid beverage that was devoid of tryptophan. This "unbalanced" mixture not only deprives the body of new tryptophan for making serotonin, it also interferes with the body's utilization of the tryptophan already in the brain. Within 5 or 6 hours after taking this formulation, subjects were found to have an 80% or more drop in plasma tryptophan levels and a concomitant "lowering" of mood.19

Researchers at the University of Texas, Houston Health Science Center gave this low-tryptophan formula (25 gm or 100 gm) to 10 healthy men in a controlled laboratory setting following a 24-hr low-tryptophan diet. They then observed the men's behavior and noted any aggressive tendencies. The men taking the 100-gm formula (lower tryptophan) showed a significant increase in aggressive responding (compared with baseline) within only 5 hours. The 25-gm formula took 6 hours to produce the same effect.20
When human subjects are fed a serotonin-
reducing beverage they become impulsive,
depressive, aggressive, and
violent within 5 or 6 hours.

VIOLENCE: INNER- AND OUTER-DIRECTED
Researchers have found that violence related to low serotonin can be either inner- or outer-directed. A group of Danish scientists measured 5-HIAA and other serotonin metabolites in the CSF of 16 men convicted of criminal homicide, 22 men who attempted suicide and 39 healthy male controls. The lowest levels of 5-HIAA were found in those men who had killed a sexual partner or had attempted suicide.21

Investigators at Columbia University evaluated personality variables and CSF 5-HIAA levels in 26 patients considered to be "self-mutilators."22 In addition to serotonergic dysfunction indicated by lower 5-HIAA levels, compared with controls, self-mutilators were found to have significantly more severe character pathology and greater lifetime aggression; they were more antisocial, and had greater impulsivity, chronic anger, and somatic anxiety.

Suicide, the ultimate expression of "auto-aggression," has long been linked to low serotonin levels. In one meta-analysis, five out of seven studies reported reduced levels of serotonin and/or 5-HIAA in the brain stems of suicide victims. Reduced brain levels were also seen in those who had attempted suicide but failed.23

As one might expect, drugs that interfere with serotonergic function can increase aggressive behavior. British scientists gave 35 healthy subjects dexfenfluramine (better known as the recently departed diet drug Redux), which is known to deplete serotonin (sometimes permanently). Using a questionnaire to assess the subjects' hostility and aggression, they found that dexfenfluramine treatment in male subjects (but not females) was associated with an increase in hostility and aggression scores.23

CHOLESTEROL AND VIOLENT DEATH
One of the more puzzling findings of recent years has been an increase in depression, suicide and violent death among people taking cholesterol-lowering drugs or on severely cholesterol-restricted diets.24-29 In other words, taking these widely recommended steps to reduce your risk of death from coronary heart disease and stroke may place you at greater risk of serious depression, suicide, or death due to violence.

How can this be? Although the exact relationships have yet to be worked out, it appears that the missing link between low cholesterol and violent death may be serotonin. This association was demonstrated most clearly in a study of juvenile cynomolgus monkeys fed a diet high in fat and either high or low in cholesterol. The animals were then observed for 8 months.

The researchers found that animals on the low-cholesterol diet were more aggressive, less affiliative, and had significantly lower CSF 5-HIAA levels compared with those on the high-cholesterol diet. "These monkeys went at it hammer and tong," says Jay Kaplan, Ph.D., who led the study. "They engaged in more contact aggression - highly charged impulsive fighting - than the other monkeys.30 Kaplan believes that people on low-cholesterol diets may be experiencing the same kind of impulsive aggression.

Kaplan raises the heretical question, "Can low-fat, low-cholesterol diets actually do some people more harm than good?" "For people who already have low serotonergic activity, a low-cholesterol diet might shove them across some threshold that makes them more likely to do things they might not otherwise do," he said.31

The precise mechanism linking cholesterol, serotonin, and aggressive behavior has yet to be elaborated, although a few hypotheses have been put forward. One hypothesis emphasizes cholesterol's role as a major component of brain cell membranes. Reducing cholesterol to too low a level may affect the fluidity and viscosity of these membranes, which contain the receptors for serotonin.29

According to another hypothesis, low cholesterol may be accompanied by a decrease in serum-free tryptophan, which results in a decrease in serotonin synthesis.To test this hypothesis, a group of Dutch researchers compared serotonin metabolism in subjects whose serum cholesterol was chronically low with another group whose cholesterol levels were normal. They found that plasma serotonin levels were 21.3% lower in the low-cholesterol group, suggesting a disruption of serotonin metabolism.32

SEROTONIN, ALCOHOL & AGGRESSION
The relationship between alcohol, depression, and violence is well-known. A high proportion of suicide victims are found to have been drinking heavily at the time of their death. Similarly, perpetrators (and victims!) of violent crimes are often intoxicated at the time of the crime.33

In animal studies, some drugs that decrease serotonin activity increase alcohol consumption. But when animals are given serotonin, tryptophan, 5-HTP, or an SSRI, their alcohol consumption drops. Rats that have been bred to prefer drinking alcohol to water have been found to have reduced serotonin activity compared with normal rats.34

Human studies have consistently demonstrated reduced alcohol intake among various groups, including social drinkers and alcohol-dependent males, taking SSRIs.34 Alcoholics have also been shown to have reduced serotonin function activity as indicated by low levels of 5-HIAA.35,36

Chronic alcohol use actually appears to increase serotonin concentration in the CSF and to facilitate serotonin activity. However, as soon as drinking stops, serotonin levels drop concurrently with the appearance of alcohol withdrawal symptoms. It is thought that the decrease in serotonin associated with withdrawal may contribute to the craving for alcohol that occurs during this period. If abstinence is maintained, serotonin levels gradually return to normal.34

(This seems to suggest that, if you're going to have a drink, take a 5-HTP capsule with it, or in advance, or on a regular basis. Although informal studies have been done to test this hypothesis, you may find yourself less likely to want a second (or third) drink. And you might have fewer withdrawal symptoms and hangovers.)

There's little doubt, though, that low serotonin activity combined with high alcohol intake is a dangerous combination. Finnish researchers have found that brain serotonin turnover is low among alcoholic, impulsive, habitually violent offenders. Not only does low serotonin seem to predispose people to alcoholism, it may also make them more aggressive, violent, and suicidal. The risk of violence or other antisocial behavior may be compounded in men whose testosterone levels are high.37,38

How does serotonin modulate these responses? Researchers Robert O. Pihl and colleagues at McGill University speculate that serotonin modifies the response to threat. In people with normal serotonin function, anxiety (the emotional response to threat) inhibits socially inappropriate responses, such as aggression. In people with depleted serotonin, however, anxiety loses its inhibitory effect while retaining its emotional intensity. As a result of this imbalance, a person might become aggressive despite the intense anxiety induced by the threat of punishment.34

Pihl et al state that people with low serotonin are likely "to appear depressed and aggressive, more driven by appetites (more motivated by food, water, sex, and drugs of abuse), and more impulsive (less able to control behavior) in the face of threat." They may also be more likely to use aggression to achieve rewards or deter punishment, and they may be less sensitive to social control of such behavior. Specifically with regard to alcohol, decreased serotonin may lead to an inability to terminate drinking once started. And if a person with low serotonin starts drinking, the result is likely to be an increase in aggressive behavior. "The combination of impulsivity [due to low serotonin] with alcohol-induced fearlessness and hyperactivity appears prone to produce aggressive acts or to culminate in victimization," the authors write.34

REVERSING SEROTONIN DEFICIENCY
If low serotonergic function can lead to aggressive and violent behavior, can reversing a serotonin deficiency restore more normal behavior? Although this area has not been studied systematically, some evidence suggests that it may. Serotonergic function can be enhanced in two basic ways: by providing the metabolic precursors for serotonin or by preventing the inactivation of serotonin that is released into the synapse.

Increasing serotonin synthesis. When taken up into neurons, the amino acids tryptophan and 5-HTP are converted into serotonin. Most studies with these amino acid precursors have involved people with depression, but the results are encouraging, particularly for 5-HTP. In one double-blind study, 5-HTP was found to be equal to an SSRI antidepressant drug in alleviating depression with fewer and less severe adverse effects. In addition to alleviating depression, 5-HTP seems to be capable of alleviating a wide range of symptoms of what Pöldinger has called the "serotonin deficiency syndrome," which includes depression, anxiety, aggression, sleep disturbances, obsessive-compulsive traits, and other behavioral manifestations.5

In another double-blind study, researchers gave tryptophan or placebo to a group of aggressive psychiatric inpatients. Injections of antipsychotics and other medications were also given, as needed, to control violent behavior. Although tryptophan treatment had no effect on the number of violent incidents, it significantly reduced the need for injections of antipsychotic and sedative drugs.39

Inhibiting serotonin inactivation. Serotonin released into the synaptic cleft is normally inactivated by either being taken back up into the neuron that released it (reuptake) or metabolized by the enzyme monoamine oxidase (MAO). Drugs that inhibit this inactivation, including the selective serotonin reuptake inhibitors (SSRIs) like Prozac (fluoxetine) and others and, to a lesser degree, MAO inhibitors, have been shown to be effective antidepressants.

A few studies suggest that SSRIs may also be able to control aggressive or violent behavior. In one study in dogs, for example, fluoxetine was found to be effective in managing dominance aggression.40 In humans, preliminary data suggest that fluoxetine may also decrease aggressive behavior and feelings of anger or hostility.41 In adult male lizards (Anolis carolinensis), fluoxetine injections significantly reduced aggressive responding in males.12

TOWARD A BETTER WORLD
Dr. Jekyll's formula dramatically exposed mankind's darker side. With the benefit of a century of neurobiological research, we can only marvel at Stevenson's insights, not only into the human character, but also into its biochemical basis. While he in all likelihood had no concept of serotonergic mechanisms, he described with astonishing accuracy the behavioral effects of serotonin depletion.

It's probably safe to say that the world would be a better, safer, happier place if everyone's serotonergic functioning could be maintained at optimal levels. Scientific evidence confirms that preventing or restoring serotonin depletion results in decreased depression, alcoholism, aggression, violence, appetite disorders, sleeping disorders, migraine headaches, and many other benefits.

While this is not to say that tryptophan or 5-HTP should be added to the drinking water, the growing body of literature on the adverse effects of reduced serotonin function, including those caused by medically sanctioned practices such as following a low-cholesterol diet, taking cholesterol-reducing drugs or serotonin-depleting drugs (e.g., fenfluramine and Redux) should turn our thoughts to serious consideration of the benefits of precursor dietary supplementation. The proven and potential benefits of enhancing serotonergic function, especially by taking serotonin precursors such as 5-HTP or tryptophan [should the latter ever become available again] are enough to allow us to visualize the day when the Hydes are permanently disabled and the good Dr. Jekylls are empowered.

References

1. Penttinen J. Hypothesis: low serum cholesterol, suicide, and interleukin-2. Am J Epidemiol. 1995;141:716-718.
2. Guggenheim CB, Foster HG Jr. Serum cholesterol and perception of anger and sadness. Psychol Rep. 1995;77:1343-1345.
3. Borne R. Serotonin: The Neurotransmitter for the '90s. Drug Topics. 1994;October 10:108.
4. Kramer P. Listening to Prozac. New York: Viking; 1993.
5. Pöldinger W, Calanchini B, Schwarz W. A functional-dimensional approach to depression: serotonin deficiency as a target syndrome in a comparison of 5-hydroxytryptophan and fluvoxamine. Psychopathology. 1991;24:53-81.
6. Lloyd K, Farley L, Deck J, Horykiewicz O. Serotonin and 5-hydroxy-indoleacetic acid in discrete areas of the brainstem of suicide victims and control patients. Adv Biochem Psychopharm. 1974;11:387-398.
7. Huber R, Smith K, Delago A, Isaksson K, Krvitz E. Serotonin and aggressive motivation in crustaceans: altering the decision to retreat. Proc Natl Acad Sci. 1997;94:5939-5942.
8. Adams C, Liley N, Gorzalka B. PCPA increases aggression in male firemouth cichlids. Pharmacology. 1996;53:328-330.
9. Ferris C, Melloni Jr R, Koppel G, Perry K, Fuller R, Delville Y. Vasopressin/serotonin interactions in the anterior hypothalamus control aggressive behavior in golden hamsters. Neurosci. 1997;17:4331-4340.
10. Amstislavskaya T, Kudryavtseva N. Effect of repeated experience of victory and defeat in daily agonistic confrontations on brain tryptophan hydroxylase activity. FEBS Lett. 1997;406:106-108.
11. Reisner I, Mann J, Stanley M, Huang Y, Houpt K. Comparison of cerebrospinal fluid monoamine metabolite levels in dominant-aggressive and non-aggressive dogs. Brain Res. 1996;714:57-64.
12. Deckel A. Behavioral changes in Anolis carolinensis following injection with fluoxetine. Behav Brain Res. 1996;78:175-182.
13. Higley J, Suomi S, Linnoila M. A nonhuman primate model of type II alcoholism? Part 2. Diminished social competence and excessive aggression correlates with low cerebrospinal fluid 5-hydroxyindoleacetic acid concentrations. Alcohol Clin Exp Res. 1996;20:643-650.
14. Popova N, Voitenko N, Kulikov A, Avgustinovich D. Evidence for the involvement of central serotonin in mechanism of domestication of silver foxes. Pharmacol Biochem Behav. 1991;40:751-756.
15. Higley J, Mehlman P, Higley S, et al. Excessive mortality in young free-ranging male nonhuman primates with low cerebrospinal fluid 5-hydroxyindoleacetic acid concentrations. Arch Gen Psychiatry. 1996;53:537-543.
16. Mehlman P, Higley J, Faucher I, et al. Correlation of CSF 5-HIAA concentration with sociality and the timing of emigration in free-ranging primates. Am J Psychiatry. 1995;152:907-913.
17. Mehlman P, Higley J, Faucher I, et al. Low CSF-HIAA concentrations and severe aggression and impaired impulse control in nonhuman primates. Am J Psychiatry. 1995;151:1485-1491.
18. Chamberlain B, Ervin F, Pihl R, Young S. The effect of raising or lowering tryptophan levels on aggression in vervet monkeys. Pharmacol Biochem Behav. 1987;28:503-510.
19. Young S, Tourjman S, Teff K, Pihl R, Anderson G. The effect of lowering plasma tryptophan on food selection in normal males. Pharmacol Biochem Behav. 1988;31:149-152.
20. Collins D, Davis C, Cherek D. Tryptophan depletion and aggressive responding in healthy males. Psychopharmacology. 1996;126:97-103.
21. Lidberg L, Tuck J, Asberg M, Scalia-Tomba G, Bertilsson L. Homicide, suicide and CSF 5-HIAA. Acta Psychiatr Scand. 1985;71:230-236.
22. Simeon D, Stanley B, Frances A, Mann J, Winchel R, Stanley M. Self-mutilation in personality disorders: psychological and biological correlates. Am J Psychiatry. 1992;149:221-226.
23. Mann J, Arango V, Underwood M. Serotonin and suicidal behavior. Ann NY Acad Sci. 1990;600:476-484.
24. Cleare A, Bond A. Does central serotonergic function correlate inversely with aggression? A study using D-fenfluramine in healthy subjects. Psychiatry Res. 1997;69:89-95.
25. Renzo R, Bertozzi B, Barbisoni P, Trabucchi M. Risk of depression is higher in elderly patients with lowest serum chholesterol values (letter). Br Med J. 1996;312:1296-1299.
26. Kunugi H, Takei N, Aoki H, Nanko S. Low serum cholesterol in suicide attempters. Biol Psychiatry. 1997;41:196-200.
27. Rybakowski J, Ainiyet J, Szajnerman Z, Zakrzewska M. The study of the relationship between cholesterol and lipid concentration and suicidal behavior in patients with schizophrenia affective illness. Psychiatr Pol. 1996;30:699-712.
28. Santiago J, Dalen J. Cholesterol and violent behavior. Arch Intern Med. 1994;154:1317-1321.
29. Hawthon K, Cowen P, Owens D, Bond A, Elliott M. Low serum cholesterol and suicide. Br J Psychiatry. 1993;162:818-825.
30. Kaplan J, Shively C, Fontenot M, et al. Demonstration of an association among dietary cholesterol, central serotonergic activity, and social behavior. Psychosom Med. 1994;56:479-484.
31. Anonymous. The cholesterol conundrum. Psychology Today. 1995;28:16.
32. Steegmans P, Fekkes D, Hoes A, Bak A, Does E, Grobbee D. Low serum cholesterol concentration and serotonin metabolism in man. Br Med J. 1996;312:221.
33. Murdoch D, Pihl R, Ross D. Alcohol and crimes of violence: present issues. Int J Addict. 1990;25:1065-1081.
34. Pihl R, Peterson J. Alcohol, serotonin and aggression. Alcohol Health Res World. 1993;17:113-117.
35. Banki C. Factors influencing monoamine metabolites and tryptophan in patients with alcohol dependence. J Neural Transm. 1981;50:89-101.
36. LeMarquand D, Pihl R, Benkelfat C. Serotonin and alcohol intake, abuse, and dependence: clinical evidence. Biol Psychiatry. 1994;36:326-337.
37. Virkkunen M, Goldman D, Linnoila M. Serotonin in alcoholic violent male offenders. Ciba Foundation Symposium. 1996;194:168-177.
38. Virkkunen M, Rawlings R, Tokola R, et al. CSF biochemistries, glucose metabolism, and diurnal activity rhythms in alcoholic, violent offenders, fire setters, and healthy volunteers. Arch Gen Psychiatry. 1994;51:20-27.
39. Volavka J, Crowner M, Brizer D, Convit A, Van Praag H, Suckow R. Tryptophan treatment of aggressive psychiatric inpatients. Biol Psychiatry. 1990;28:728-732.
40. Dodman N, Donelly R, Shuster L, Mertens P, Rand W, Miczek K. Use of fluoxetine to treat dominance aggression in dogs. J Am Vet Assoc. 1996;209:1585-1587.
41. Fuller R. Fluoxetine effects on serotonin function and aggressive behavior. Ann NY Acad Sci. 1996;794:90-97.

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 Titel:
Indlæg: 29 aug 2006 14:39 
Jeg synes det er fint at informere om hvilke kosttilskud mm. man kan indtage for at kompensere for et stofs skadelige virkninger, men sådan når alt kommer til alt ligger antallet af mennesker, der egentlig gør brug af sådan noget, på et meget lille sted.

Jeg har ihvertfald opfattelsen af, at det er ret få folk herinde der går op i at indtage kosttilskud osv. for at mindske evt. skadevirkninger fra stoffer. Også af de mere erfarne brugere.


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Indlæg: 29 aug 2006 16:20 
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Insane psychedelia user!
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Tilmeldt: 03 aug 2005 09:17
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Pharm skrev:
Jeg synes det er fint at informere om hvilke kosttilskud mm. man kan indtage for at kompensere for et stofs skadelige virkninger, men sådan når alt kommer til alt ligger antallet af mennesker, der egentlig gør brug af sådan noget, på et meget lille sted.

Jeg har ihvertfald opfattelsen af, at det er ret få folk herinde der går op i at indtage kosttilskud osv. for at mindske evt. skadevirkninger fra stoffer. Også af de mere erfarne brugere.


Man kan tvinge hesten til truget, men ikke tvingen den til at drikke. Jeg ser dog altid en enkelt eller mere i diverse tråde, som eksempelvis har brugt 5-htp - så nogen bruger vel rådene.


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Indlæg: 29 aug 2006 16:22 
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Tilmeldt: 05 dec 2005 02:14
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Jeg går i gang med læsningen senere i dag. Der står trods alt en del :)


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Indlæg: 30 aug 2006 17:54 
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shinsou skrev:
Jeg går i gang med læsningen senere i dag. Der står trods alt en del :)


@Malkavian/andre: Det kunne evt. være en idé at skrive et kort dansk resumé af artiklerne?

F.ex. at B-vitamin, C-vitamin, folin-syre (rigtigt oversat?) og magnesium er nødvendige for metabolisering af tryptophan.
Eller at der findes mest tryptophan i rødt kød, mejeri-produkter, nødder, frø, bananer, soya-bønner, soya-produkter, tun, skalddyr og kalkun.


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