Here we found that low DHA status is a significant risk factor for suicide death among active duty US military. Nearly all US military personnel had low n-3 HUFA status in comparison to North American 13
, Australasian 14
, Mediterranean 15
and Asian 8
populations. The low amounts and narrow range of DHA in this US Military population in comparison to world and US diversity, made detection of an association difficult and impaired the evaluation of risk relationships among people with higher n-3 HUFA status. For example, the lowest DHA status in a population of suicide attempters in China appeared to be higher than nearly all the US military personnel reported here 8
. Chinese subjects in the lowest quartile of DHA status in erythrocytes (mean 2.72% range 0.56–3.72) had a higher odds of a suicide attempt (OR =4.76, 95%CI, 1.67–14.28, p<0.0003) compared to the highest quartile (mean 6.9%, range 6.15–8.94) 8
. When compared across these two populations, the lowest DHA status may be associated with a 5–6 fold increased risk of suicidal behaviors compared to the highest status. The maximal benefit may not have been assessed in this sample of US military personnel.
Increased risk for suicide is likely due to multiple social, psychiatric and environmental risk factors underscoring the complexity of psychological health issues among service members. The relative impact of low DHA status on increased suicide risk (62%) can be put into perspective in comparison to the relative impact of severe combat stress or prior mental health problems on increased suicide risk. Personnel with a positive response to “Did you see wounded, killed or dead coalition during deployment?” had an increased risk of suicide death by 54%. The strength of the relationship between more numerous prior mental health visits and increased risk of suicide death was also similar to that of low DHA status.
Some of the limitations inherent in this retrospective analysis were inability to characterize neuropsychiatric symptoms, stress exposure, traumatic brain injury, alcohol use or other potential risk factors and assessment of reverse causality. We noted that an effect of storage time was found for DHA%; mean (SD): 1.32 (0.53) in 2008 and 1.03 (0.40) in 2002, p<0.0001, however the time of storage was matched for cases and controls. Although unlikely, it is possible that DHA was selectively degraded among cases as compared to controls. Although we would have preferred to use multiple serum samples over time the use of a baseline single serum sample robustly PUFA status over serial samples over 12 months duration 16
As this is a case control study, we must consider the possibility that the presence of a mental illness or substance misuse has changed dietary habits or tissue status and lowered DHA status. However here we found no differences in fatty acid status comparing personnel with and without mental health and substance abuse diagnoses and was thus unlikely to suggest reverse causality for suicides. In addition, reverse causality for depression and n-3 HUFA deficiencies is unlikely as meta-analyses of randomized placebo controlled trials have reported robust treatment efficacy.
We caution that causality for higher n-3 HUFA status in preventing or treating suicide cannot be inferred from this study alone, however this interpretation is supported by a randomized placebo controlled trial of 2 g/d of EPA and DHA finding a 45 % reduction in suicidal thinking and a 30% reduction in depression among patients with recurrent self harm 10
. Large treatment effect sizes for n-3 HUFAs among subjects with severe depressive symptoms have been reported in several meta-analyses of randomized placebo controlled trials 17, 18, 19
. Severe depressive symptoms are a risk factor for suicidal thinking 20
. Epidemiologic data also indicate that low fish consumption is associated with increased risk for suicide. In a 17-yr follow-up of 256,118 Japanese subjects 5
, subjects eating fish less than every day had a higher risk of suicide compared to subjects ate fish daily. Among 1,767 Finnish subjects, consuming fish less than twice per week was associated with higher risk of depressive symptoms and suicidal thinking 7
. Low DHA status also predicted a 3.4 fold greater risk of a new suicide attempt over more than 800 days 9
. These future suicide attempters had greater activity in the anterior cingulate and limbic forebrain in resting PET scans quantifying regional glucose uptake, 21
consistent with the suspected pathophysiology of severe depression and post traumatic stress disorder. Over a 10-fold range of DHA status (0.7 – 7.1% DHA in phospholipid) lower DHA status robustly predicted this regional hyperactivity indicating that low DHA status is may potentially be associated with greater limbic system activity 21
. Mann et al 22
have linked suicidal and aggressive behaviors and impulsivity to reduced prefrontal cortical activity on positron emission tomography (PET). DHA supplementation increases prefrontal activity during sustained attention in a dose responsive manner 23
While this current study could not assess neurobiological mechanisms, several are plausible. Serotinergic, dopaminergic and noradrenergic deficits and overactive stress responses of the hypothalamic-pituitary-adrenal (HPA) axis are implicated in the neurobiology of suicidal behavior 22
. In piglets, dietary deficiencies of DHA and AA for 18 days decreased serotonin, dopamine and their metabolite levels in frontal cortex by 50% 24
. In mice, chronic stress induced a 40–65% decrease in serotonin and norepinepherine levels in frontal cortex25
. These were completely reversed by EPA and DHA supplementation. Deficits in synaptoneogenesis and neural plasticity caused by DHA deficiencies may underlie these observations 26
. Observational studies in humans are consistent with these animal studies: lower plasma DHA levels correlated with lower cerebrospinal fluid (CSF) levels of the serotonin metabolite 5-hydroxyindolacetic acid among healthy controls 27
and lower levels of CSF-corticotrophin releasing factor in perpetrators of domestic violence 28
Unexpectedly we found that higher DGLA status was associated with lower risk of suicide death. In contrast, Virkkunen et al reported that higher phospholipid DGLA levels were associated with a greater likelihood of suicide attempts and violent homicide 29
and higher DGLA in adipose has been associated with greater depressive symptoms 30
. Additionally we found that lower levels of stearic acid (18:0) were associated with greater risk of suicide, and that higher levels of palitolenic (16:1) and cis-vaccenic acids (18:1n-7) were associated with lower risk of suicide, the implication of these findings are not clear as psychotropic effects of saturated and monounsaturated fatty acids have not been reported to our knowledge.
Rapidly rising suicide rates are a sentinel for increased impairment of fighting force efficacy due to mental illness 31
. The greatest cause of inpatient bed utilization in the US Military is mood disorders, primarily major depression with suicidal risk and adjustment disorders 32
. In response, the US Army has initiated a $50 million observation study of enrolling 120,000 subjects per year for five years 33
with the primary purpose of identifying “modifiable risk and protective factors related to mental health and suicide.” Our identification of low DHA serum status as a significant risk factor for suicide deaths can complement this effort. The low n-3 HUFA status is likely due to a combination of several factors including excess omega-6 linoleic acid consumption and deficits in seafood consumption from both foods consumed at US military dining facilities, from available restaurants and choices made at home 34
Low DHA status can be readily reversed using low cost dietary interventions14
that are likely to have multiple beneficial health effects 35
. The American Psychiatric Association already recommends consumption of at least 1 gm per day of n-3 HUFAs for all patients with psychiatric disorders 19
. The FDA has determined that up to 3 gm of n-3 HUFAs is generally recognized as safe. The evaluation of efficacy of these levels of n-3 HUFAs in the primary prevention of suicide attempts, or as treatment following suicidal behaviors, merits consideration the US military.