The U.S. military is showing interest in the potential preventive benefits of supplemental omega-3s from fish oil in preventing or treating depression and traumatic brain injury.
Along with traumatic brain injury, PTSD is the signature wound – an invisible one – suffered by service men and women in Iraq and Afghanistan.
PTSD afflicts a substantial minority of people who experience domestic abuse, rape, or serious accidents.
Now, a new review of the evidence on omega-3s' role in the development of post-traumatic stress disorder encourages the idea that fish fats may help prevent PTSD or reduce its severity.
The paper's author reviewed lab research into links between omega-3s and the brain functions associated with PTSD, and had this to say about the results of a small, uncontrolled clinical trial published in 2010:
“The results of an open-label pilot trial of injured patients admitted to the intensive care unit suggest that omega-3 fatty acid supplementation immediately after accidental injury can reduce subsequent PTSD symptoms.” (Matsuoka Y 2011)
The three-month trial was small – just 11 people completed it – and not placebo controlled, but it had several significant, encouraging outcomes (Kitamura T et al. 2010).
Judging by prior research into the biological roots of PTSD, its positive outcomes seem entirely plausible … see “Prior evidence prompted the pilot trial” and “PTSD starts with memory-anxiety attachment”, below.
Pilot clinical trial points to omega-3 potential for PTSD
The researchers recruited 24 accident-injured patients at an intensive care unit in Tokyo, and 11 completed the study.
The volunteers agreed to take fish oil pills – providing 1470mg of DHA and 147mg of EPA – daily for 12 weeks.
They also agreed to forgo any psychiatric drugs except for minimal use of antidepressants, and to undergo psychological examinations at the outset and again after three months.
(During the trial three patients received psychiatric drugs … interestingly, two of the three developed PTSD or major depressive disorder.)
In addition, the participants gave blood samples at the beginning and end to confirm their use of the fish oil supplements and to allow the researchers to look for connections between omega-3 blood levels and development of PTSD.
The results were positive. On average the patients' scores on standard average PTSD tests were significantly lower than would be expected in similar accident-injured patients.
Importantly, only the two patients who had low DHA blood levels at the trial's outset developed PTSD or major depression by the end of the trial.
This suggests that a person's blood level of DHA just before a trauma occurs is critical to preventing PTSD … and that giving people omega-3s after a trauma has occurred may provide less benefit.
As the Tokyo team wrote, “Given the increase in the DHA level observed in both of these patients after supplementation of omega-3 fatty acids, the baseline [omega-3 DHA blood level] in daily life might be important, irrespective of the addition of omega-3 fatty acids after an accident or other trauma]. (Kitamura T et al. 2010)
Because of its small size and the lack of a control group taking placebo pills, definitive conclusions must await the results of large, well-controlled trials.
Fortunately, the Tokyo team has already started a larger, randomized, controlled trial to help determine the power of omega-3s to prevent PTSD … or not.
This pilot study provides promising support for the hypothesis – proven plausible by animal experiments (see “Prior evidence prompted the pilot trial”, below) – that starting omega-3 DHA supplements shortly after accidental injury may help reduce PTSD severity.
The Japanese team's findings hold major public mental health implications because PTSD or depression after accidental injury affects millions worldwide, and not just those in combat zones.
And as they wrote, “… our findings may provide a new prevention strategy against the development of PTSD.” (Kitamura T et al. 2010)
Prior evidence prompted the pilot trial
The authors of the 2010 pilot clinical trial described above were inspired by prior research in rodents to test omega-3 fish oil in human accident victims.
Those rat and mouse studies show that omega-3 DHA helped rodents' brains respond to physical or psychological brain trauma more healthfully and resiliently … and importantly, they pinpointed plausible biochemical reasons.
Specifically, investigations in animals reveal that short-term feeding of omega-3s (EPA + DHA) fish oil “up-regulates” growth of new brain cells (Beltz BS et al., 2007).
They also show that dietary omega-3s raise rats' levels of a key compound called brain-derived neurotrophic factor (BDNF) … which promotes survival and growth of brain cells (Wu A et al. 2004).
And another team found that adding omega-3 DHA to brain cells taken from the hippocampus enhanced connectivity among these neurons via increased “extension and branching” (Calderon F et al. 2004).
PTSD starts with memory-anxiety attachment
Like all short-term memories, ones associated with fear – like experiencing a car accident or roadside bomb – begin in the hippocampus, where significant ones get converted into long-term memories and transferred to the brain's cortex for permanent storage.
This fact raises the possibility that by enhancing brain cell growth and “plasticity” in the hippocampus, doctors might help prevent fearful memories from becoming the kinds of ingrained, intrusive, anxiety-provoking thoughts that characterize PTSD.
That hypothesis received crucial support from a study in mice in which brain cell growth in the hippocampus was artificially suppressed (Kitamura T et al. 2009).
In these mice, preventing brain cell growth in the hippocampus was accompanied by a prolonged period of “associative fear memory” … the same problem that underlies PTSD in people.
(The term “associative fear memory” simply means a memory that's associated with fear. Psychiatrists call this process “contextual fear conditioning”.)
In contrast, enhancing brain cell growth in the hippocampus (by having the animals exercise voluntarily on a wheel) sped up the rate at which those associations between a memory and ongoing fear decayed … without any loss of memory.
Accordingly, scientists hypothesized that promoting brain cell growth early in the transition period that converts a short-term memory to long-term status might aid clearance of “fear memory” in people.
Bousquet M, Gibrat C, Saint-Pierre M, Julien C, Calon F, Cicchetti F. Modulation of brain-derived neurotrophic factor as a potential neuroprotective mechanism of action of omega-3 fatty acids in a parkinsonian animal model. Prog Neuropsychopharmacol Biol Psychiatry. 2009 Nov 13;33(8):1401-8. Epub 2009 Jul 24.
Calderon F, Kim HY. Docosahexaenoic acid promotes neurite growth in hippocampal neurons. J Neurochem. 2004;90(4):979-988.
Cysneiros RM, Ferrari D, Arida RM, Terra VC, de Almeida AC, Cavalheiro EA, Scorza FA. Qualitative analysis of hippocampal plastic changes in rats with epilepsy supplemented with oral omega-3 fatty acids. Epilepsy Behav. 2010 Jan;17(1):33-8. Epub 2009 Dec 6.
Feng R, Rampon C, Tang YP, et al. Deficient neurogenesis in forebrain-specific presenilin-1 knockout mice is associated with reduced clearance of hippocampal memory traces. Neuron. 2001;32(5):911-926.
Kitamura T, Saitoh Y, Takeshima N, et al. Adult neurogenesis modulates the hippocampus-dependent period of associative fear memory. Cell. 2009;139(4):814-827.
Logan AC. Omega-3 and BDNF regulation: eicosapentaenoic acid may play a key role in limitation of CNS injury. J Neurotrauma. 2008 Dec;25(12):1499. No abstract available.
Matsuoka Y, Nishi D, Nakajima S, Yonemoto N, Hashimoto K, Noguchi H, Homma M, Otomo Y, Kim Y. The Tachikawa cohort of motor vehicle accident study investigating psychological distress: design, methods and cohort profiles. Soc Psychiatry Psychiatr Epidemiol 2009, 44:341.
Matsuoka Y, Nishi D, Yonemoto N, Hamazaki K, Hamazaki T, Hashimoto K. Potential role of BDNF in the omega-3 fatty acid supplementation to prevent posttraumatic distress after accidental injury: An open-label pilot study. Psychothear Psychosom in press.
Matsuoka Y, Nishi D, Yonemoto N, Hamazaki K, Hashimoto K, Hamazaki T. Omega-3 fatty acids for secondary prevention of posttraumatic stress disorder after accidental injury: an open-label pilot study. J Clin Psychopharmacol. 2010 Apr;30(2):217-9.
Peters J, Dieppa-Perea LM, Melendez LM, Quirk GJ. Induction of Fear Extinction with Hippocampal-Infralimbic BDNF. Science 2010, 328:1288-1290.
Rao JS, Ertley RN, Lee HJ, DeMar JC Jr, Arnold JT, Rapoport SI, Bazinet RP. n-3 polyunsaturated fatty acid deprivation in rats decreases frontal cortex BDNF via a p38 MAPK-dependent mechanism. Mol Psychiatry. 2007 Jan;12(1):36-46. Epub 2006 Sep 19.
Squire LR. Memory and Brain. Oxford: Oxford University Press; 1987.
Venna VR, Deplanque D, Allet C, Belarbi K, Hamdane M, Bordet R. PUFA induce antidepressant-like effects in parallel to structural and molecular changes in the hippocampus. Psychoneuroendocrinology. 2009 Feb;34(2):199-211. Epub 2008 Oct 10.
Wu A, Ying Z, Gomez-Pinilla F. Dietary omega-3 fatty acids normalize BDNF levels, reduce oxidative damage, and counteract learning disability after traumatic brain injury in rats. J Neurotrauma. 2004;21(10):1457-1467.
Wu A, Ying Z, Gomez-Pinilla F. Dietary omega-3 fatty acids normalize BDNF levels, reduce oxidative damage, and counteract learning disability after traumatic brain injury in rats. J Neurotrauma. 2004 Oct;21(10):1457-67