Bracha, Dr. Stefan

Chronicle, Dr. Edward

English

Cognitive Sciences ePrint Archive

Dietary-Free Glutamate: 
Implications for Research on  
Fear-Overconsolidation and PTSD 
944Volume 11 — Number 1 CNS Spectrums — January 2006
To the Editor:                      November 16, 2005
The focus on glutamate neurotransmission 
presented in the October 2005 CNS Spectrums1,2 
was a turning point in the conceptualization of 
overconsolidational fear disorders, such as post-
traumatic stress disorder (PTSD). We would like to 
draw attention to a potential confounding factor 
that can be controlled in future studies. Dietary 
free glutamate (DFG) is not only a common flavor 
enhancer (most often as monosodium glutamate 
[MSG]) in several American fast-food chains and 
as an unlabeled ingredient in many condiments 
and prepared foods, but also occurs naturally in 
common foods, such as hard cheeses and mush-
rooms, and in other foods as hydrolyzed protein 
or as a result of fermentation.3,4 DFG additives 
originated in Japan following the discovery that 
the fermented “1,000 year-old egg” and some 
other highly prized Asian condiments (utilized for 
enhancing the taste of low protein foods) con-
tained very high levels of free glutamate. 
 Free glutamate molecules are released by ani-
mal protein and receptors for detecting the taste 
of glutamate were evolutionarily highly con-
served during rodent, primate, and pre-paleo-
lithic human evolution5,6 since dietary animal 
protein was scarce among these omnivore spe-
cies. Studies of knockout mice and of macaques 
have demonstrated the existence of glutamate 
receptors (originally known as “umami” recep-
tors) on the lingual surface of non-human pri-
mates and rodents.5
 Unlike food additives, such as sodium and 
sugar, the Food and Drug Administration has 
not established a maximum recommended daily 
allowance, nor required mandatory labeling for 
DFG. The consensus in the nutrition research 
literature is that DFG food additives are safe for 
the “majority” of individuals when consumed 
at “normal levels.”3 However, what is meant by 
“normal levels” of DFG intake and the percent-
age of individuals who experience DFG-trig-
gered symptoms has never been specified. DFG 
challenge studies conducted to date (all food 
industry-funded) only include volunteers who 
are young, self-selected, and otherwise healthy.4
 We are unaware of any published DFG chal-
lenge studies of individuals with disorders, 
such as PTSD (or even bipolar depression). It is 
unknown whether DFG consumption triggers a 
relapse of psychiatric disorders which respond to 
Glutamate release inhibitors (GRIs) (or which are 
comorbid with MSG-triggered migraine or MSG-
triggered medically unexplained muscle pain).7 
Additionally, removal of perisynaptic glutamate 
is an active process. It is unknown whether DFG 
consumption triggers a relapse in psychiatric 
disorders in which mitochondrial neuroenerget-
ics8 or glial dysfunction may be present.
 A functional magnetic resonance imaging 
study of healthy humans has demonstrated the 
activation of the insular/opercular cortex, the cau-
dolateral orbitofrontal cortex, and a part of the 
rostral anterior cingulate cortex in response to 
DFG.6 Similar functional imaging studies in mood 
disorders and overconsolidational disorders, 
especially warzone-related PTSD, are warranted. 
 Diet has been a common confounding factor 
in psychiatric research. Future clinical and func-
tional imaging studies involving central nervous 
system glutamate may be strengthened by using 
a comprehensive diet checklist (H.S. Bracha, MD, 
The Dietary Free Glutamate Exposure Checklist, 
unpublished research instrument, 2005). to con-
trol for recent DFG consumption of all research 
participants. Dietary consumption of supra-
physiological levels of glutamate in the United 
Letter to the Editor
945Volume 11 — Number 1 CNS Spectrums — January 2006
States has dramatically increased over the last 
60 years. 
 After World War II flavoring of United States mil-
itary combat rations with DFG additives began. 
Only recently has DFG flavoring been removed 
from the military Unitized Group Rations and the 
Meals Ready to Eat used by US combat troops.10 
The prevailing explanations proposed for the 
increase in the prevalence of PTSD in Vietnam vet-
erans as compared with World War II veterans are 
mostly psychosocial. However, we speculate that 
an additional factor contributing to this increase 
may be the several-fold rise in DFG concentration 
in the diet of American active-duty military person-
nel that began in 1946. On a more clinical note, 
research can examine the predictions that the his-
tory of “MSG sensitivity” may predict a favorable 
GRI response and also that, a low-glutamate diet 
may offer a benign GRI augmentation option, or a 
GRI alternative for psychiatric patients for whom 
GRIs may pose a problem.
Sincerely,
H. Stefan Bracha, MD
Honolulu, HI, and 
Edward P. Chronicle, PhD
Manoa, HI
REFERENCES
1. Cortese BM, Phan KL. The role of glutamate in anxiety and related 
disorders. CNS Spectr. 2005;10:820-830.
2. Gillespie CF, Ressler KJ. Emotional learning and glutamate: 
Translational perspectives. CNS Spectr. 2005;10:831-839.
3. Federation of American Societies of Experimental Biology. Analysis 
of adverse reactions to monosodium glutamate (MSG). Washington, 
DC: FASEB;1995.
4. Geha RS, Beiser A, Ren C, Patterson R, Greenberger PA, Grammer 
LC et al. Review of alleged reaction to monosodium glutamate and 
outcome of a multicenter double-blind placebo-controlled study. J 
Nutr. 2000;130(4S suppl):1058S-1062S.
5. Zhao GQ, Zhang Y, Hoon MA, Chandrashekar J, Erlenbach I, Ryba 
NJ et al. The receptors for mammalian sweet and umami taste. Cell. 
2003;115:255-266.
6. de Araujo IE, Kringelbach ML, Rolls ET, Hobden P. Representation of 
umami taste in the human brain. J Neurophysiol. 2003;90:313-319.
7. Smith JD, Terpening CM, Schmidt SO, Gums JG. Relief of fibromyal-
gia symptoms following discontinuation of dietary excitotoxins. Ann 
Pharmacother. 2001;35:702-706.
8. Konradi C, Eaton M, MacDonald ML, Walsh J, Benes FM, Heckers 
S. Molecular evidence for mitochondrial dysfunction in bipolar disor-
der. Arch Gen Psychiatry. 2004;61:300-308.
9. United States Department of Defense. Special Briefing on Objective 
Force Warrior and DoD Combat Feeding Program. Available at: 
http://www.dod.mil/transcripts/2002/t05232002_t0523cfp.html . 
Accessed: November 13, 2005.
Dr. Bracha is a research psychiatrist at the National Center for 
PTSD at the Department of Veterans Affairs in the Pacific Islands 
Health Care System at Spark M. Matsunaga Medical Center  in 
Honolulu, Hawaii. Dr. Chronicle is associate professor in the 
Department of Psychology at the University of Hawaii at Manoa.
Disclosure: Drs. Brach and Chronicle do not have an affiliation 
with or financial interest in any organization that might pose a 
conflict of interest. This material is based upon work supported 
in part by the Office of Research and Development, Medical 
Research Service, Department of Veterans Affairs, VA Pacific 
Islands Health Care System, Spark M. Matsunaga Medical Center. 
Support was also provided by a National Alliance for Research on 
Schizophrenia and Depression Independent Investigator Award, 
and the VA National Center for PTSD.
Please send letters to the editor to: CNS Spectrums, c/o 
Jack M. Gorman, MD, 333 Hudson St., 7th Floor, New 
York, NY 10013; E-mail: sb@mblcommunications.com.
Letter to the Editor


Dietary-Free Glutamate: Implications for Research on Fear-Overconsolidation and PTSD

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