Nutritional Influences on Illnessby Melvyn R, Werbach, MDtip@third-line.com

Aggressive Behavior andL-Tryptophan

Serotonin, a major neurotransmitter, has been foundto play an important role in modulating aggressivebehavior. Impulsive, violent, and suicidal behaviors haverepeatedly been shown to be associated with a reduction inserotonergic activity in the central nervous system.'

Alcohol ingestion, which is well known to magnify thepotential for aggression,̂ appears to transiently increasebrain serotonin tumover.^ While initially this effect wouldimprove mood, it results in further serotonin depletion,thereby promoting aggressive behavior.

Tryptophan is the dietary precursor of serotonin, andthe combination of excessive alcohol intake and a low-tryptophan diet has been found to be associated with bothdecreased brain serotonin and increased aggression/ Ina study of alcoholic impulsive offenders with antisocialpersonality disorder, aggressive behavior was found to berelated to depressed cerebrospinal fluid (CSF) serotoninlevels. Moreover, depressed CSF levels of a serotoninmetabolite (5-HIAA) were associated with elevated CSFtestosterone levels. While the 5-HIAA levels were relatedto impulsivity, the CSF testosterone levels were related toaggressiveness and interpersonal violence.^

In addition to alcoholics, depressed CSF 5-HIAA levelshave also been found in suicidal/aggressive patients andviolent offenders who were not alcoholic.^-^

Several lines of evidence suggest that the amount oftryptophan in the diet relates closely to aggressive behavior.For example, rats given a diet almost lacking in tryptophandevelop aggressive behavior towards mice.^ In humans.

tryptophan intake is inversely correlated with aggressivetraits^'" Moreover, bimodal seasonal emotional patternsare related to plasma L-tryptophan availability, and thisdata matches known seasonal patterns forthe prevalence ofviolent suicide and depression."

Tryptophan must compete with other large neutralamino acids to cross the blood-brain barrier; therefore,the ratio of the amount of tryptophan to the amount ofcompeting amino acids (tryptophan ratio) may providea rough indication of the availability of tryptophan in thebrain for conversion into serotonin. Kitahara has calculatedthe dietary tryptophan ratio for 18 European countries toattempt to relate it to homicide rates. While initially nocorrelation was found between tryptophan ratios andhomicide, once social and cultural differences werecontrolled for, low tryptophan ratios were indeed found tobe associated with high homicide rates.'̂

A more direct method of examining the relationshipbetween the tryptophan ratio and aggression is by measuringthe actual ratio in the blood plasma. When a group ofdepressed alcoholics was evaluated in this manner, thosewith a history of aggression - including suicide attempts -also had the lowest tryptophan ratios.'*

L-Tryptophan SupplementationIf a low tryptophan ratio is associated with aggressive

behavior, will tryptophan supplementation reduce thatbehavior? Dietary tryptophan was manipulated in socialgroups of verve! monkeys by providing them with amino

154 TOWNSEND LETTER - FEBRUARY/MARCH 2009

acid mixtures that were tryptophan-free, nutritionallybalanced, or excessively high in tryptophan. These mixtureswere shown to have a marked effect on plasma tryptophanlevels.

During spontaneous activity, the only effect of thedifferent mixtures was increased aggression in the males onthe tryptophan-free mixture. During competition for food,however, while the tryptophan-free mixture continued toincrease male aggression, the high-tryptophan mixturereduced aggression in both males and females.'•* Thesedata suggest that tryptophan supplementation may be mosteffective in reducing aggression during times of stress.

When hospitalized male schizophrenics were givenL-tryptophan, only those patients with high levels ofhostility and a high lifetime frequency of aggressiveincidents benefited; these patients showed a lessening ofhostility and depression, a reduction in ward incidents, andimprovement on a standardized psychiatric rating scale.'^In another study of 20 aggressive patients, while 6 gramsof tryptophan daily for one month failed to reduce thenumber of violent incidents, it significantly reduced theneed for potent medications to control violent or agitatedbehavior.""

The rate of firing of serotonergic neurons in the brainincreases as the level of behavioral arousal increases;thus increased serotonin levels would be more likely toinfluence brain function at higher levels of arousal. Indeed,this fact probably explains why the vervet monkeys onlyresponded to tryptophan supplementation when they wereput under competitive stress. It also may explain whyaltered tryptophan levels failed to affect aggression in astudy of normal human males, while overaroused, hostile,and aggressive psychiatric patients responded well.

Both clinical and anecdotal evidence suggest that 500 to1,500 mg of supplementary tryptophan, taken at bedtime ona regular basis, is frequently sufficient to relieve symptomsdue to serotonin-deficiency. Surprisingly, higher dosagesmay not be as effective, due to activation of tryptophanpyrrolase, a key enzyme in the metabolism of tryptophan inthe liver.

Since niacinamide, a form of vitamin B3, inhibits livertryptophan pyrrolase, the addition of at least 100 mg ofthe vitamin with each meal should increase tryptophan'sefficacy. Similarly, since vitamin B6 activates the enzymethat converts tryptophan to serotonin, 25 to 50 mg of this

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Nutritional Influences on Illnesscontinued from page 155

vitamin once or twice daily with meals may also increaseits efficacy.'^

In the conversion of tryptophan to serotonin, theintermediate step is its conversion to 5-hydroxytryptophan{5-HTP). Surprisingly, supplementation with 5-HTF'may increase aggressive behavior, apparently because,while tryptophan appears to exclusively enhance theserotonergic system, 5-HTP also appears to enhance thecatecholaminergic system.'"

Dr. Werbach cautions thai the nulritional treatment of illness, shouldbe supervised by physicians or other practitioners whose trainingprepares them to recognize serious illness and to integrate nutritionaiinterventions safely into the treatment plan.

Notes1. Roy A et al. Monoamines, glucose metabolism, aggression towards self and

others. Ini I Neuroso, 1988;4I|3-4):261-4.2. Uiu MA, Pihl RO. Alcuhol iind the. Tdyiof aggression paradigm: a repeated

measures study. / Stud Alcohol. 1994;5516):701-6.3. Goodwin FK. Alcoholism research: delivering on the promise. Public Health

Rep. 1988;103(6):569-74.4. Pihl RO et al. Acute effect of altered tryptophan levels and alcohol on

aggression in normal human males. Psychopharmacology. t995;H9:353-60.

5. Virkkunen M et al. CSF binchemistfies, glucose melabolism, and diurnalaclivity rhythms in akoholic. violent offenders, fire setters, dnd healthyvolunteers. Arch Gen Psychiatry. 1994;5l(1):20-27.

6. Linnoila VMI et al. Aggression, suicidality, and serotonin. I Clin Psychiatry.1992;53(suppl):46.51.

7. Van Praag HM. Affective disorders and aggression disorders: evidence for iicommon biological mechanism. Suicide Life Threat Behav. 1986; 16(2): 103-132.

8. Gianimanco S et al. Short term diet of precooked corn meal almost lackingin tryptophan and interspecific rat-mouse aggressive behavior. Arch IntPhysiol Biochem. 1990;98i11:23-26.

9. Cleare AJ, Bond Al. Effects of alterations in plasma tryptophan levels onaggressive feelings. Arch Ce/i Psychialry. 1994;51:1004-100.î.

10. Cleare A), Bond AJ. The effect of tryptophan depletion and enhancementon subjective and behavioral aggression in normal male subjects.Psychopharmacology. 1995;! 18:72-81.

11. Maes M et a!. Seasonal variation in plasma L-tryprophan availability inhealthy volunteers: relationships in violent suicide occurrence. Arch GenPsychialry. 1995;52:937-94r..

12. Kiiahara M. Dietary tryptophan ralio and homicide in Western and SouthernEurope, y Ort/iomo) Med. 1986;1(1):13-16.

I 3. Branchey L et al. Depression, suicide and aggression in alcoholics and iheirrelationship to plasma amino acids. Psychiatry Res. 1984:12(3):219-226.

14. Chamberlain B et al. The effect of raising or lowering tryptophan levels onaggression in vervet monkeys. Pharmacol Biochem Behav. 1987;28(4¡:50.3-510.

15. Morand C e! al. Clinical response of aggressive schizophrenics to oraltryptophan. Slo/Psych/atry. 1983;18(5l:575-578.

16. Volavka J et al. Tryptophan treatment of aggressive psychiatric patients. BiolPsychiatry. 1990;28(81:728-732.

17. South [. L-Tryptophan: Natuie's answer to Prozac*. Vitamin Research News.Apfil 2OO4;18(3):l-2,10-11.

18. Raleigh M). Differential behdvioral effects of tryptophan and5-hydroxytryptophan on vervet monkeys: influence of catee ho lam in erg i i;systems. Psychopharmacolotiy (Berlin) 1987:93(1):44-50.

If you treat patients with psychological symptoms, you will want a copyoí Dr. Werbach's thoroughly revised and expanded second editionof Nutritional Influences on Mental Illness, fot more information onhis books, see the Third Line Press web page (www.third-line.com)or contact Third Line Press directly (4751 Viviana Drive, Tarzana,California 91356, USA; 818-996-0076; fax: 818-774-1575; tlp@third-line.com). ^

TOWNSEND LETTER - FEBRUARY/MARCH 2009