The authors have declared that no competing interests exist.
Conceived and designed the experiments: JCU JRH MDL. Performed the experiments: JCU JRH MDL. Analyzed the data: JCU RPH MLS DTG RJU MH. Wrote the paper: JCU MLS. Critically revised manuscript for important intellectual content: DTG RPH MDL RJU MH JRH MLS.
Considering that epidemiological studies show that suicide rates in many countries are highest in the spring when vitamin D status is lowest, and that low vitamin D status can affect brain function, we sought to evaluate if a low level of 25-hydroxyvitamin D [25(OH)D] could be a predisposing factor for suicide.
We conducted a prospective, nested, case-control study using serum samples stored in the Department of Defense Serum Repository. Participants were previously deployed active duty US military personnel (2002–2008) who had a recent archived serum sample available for analysis. Vitamin D status was estimated by measuring 25(OH) D levels in serum samples drawn within 24 months of the suicide. Each verified suicide case (n = 495) was matched to a control (n = 495) by rank, age and sex. We calculated odds ratio of suicide associated with categorical levels (octiles) of 25(OH) D, adjusted by season of serum collection.
More than 30% of all subjects had 25(OH)D values below 20 ng/mL. Although mean serum 25(OH)D concentrations did not differ between suicide cases and controls, risk estimates indicated that subjects in the lowest octile of season-adjusted 25(OH)D (<15.5 ng/mL) had the highest risk of suicide, with subjects in the subsequent higher octiles showing approximately the same level of decreased risk (combined odds ratio compared to lowest octile = 0.49; 95% C.I.: 0.315–0.768).
Low vitamin D status is common in active duty service members. The lowest 25(OH)D levels are associated with an increased risk for suicide. Future studies could determine if additional sunlight exposure and vitamin D supplementation might reduce suicide by increasing 25(OH) D levels.
Suicide is a global health concern and ranks as one of the leading causes of death worldwide. Among the United States military, suicide has become a critical issue. The increased risk of suicide in areas with less sun exposure, and during the spring when 25-hydroxyvitamin D [25(OH)D] levels are at their lowest
There is increasing evidence that vitamin D influences brain function
To evaluate the possibility that lower vitamin D status could be associated with increased risk of suicide, we examined the 25(OH)D levels in archived serum obtained from service members who subsequently died by suicide and compared them to matched controls. We predicted that suicide risk would follow a pattern similar to what is often seen with other nutrient deficiencies, i.e., an increased risk would occur below some threshold value of vitamin D status.
The study population included active duty service members from the United States military who had been deployed and for whom blood serum was available from the Defense Medical Surveillance System (DMSS), Armed Forces Health Surveillance Center (AFHSC). From this population, all officially verified suicides occurring between 2002 and 2008 who had blood sampled within 24 months of death were included as cases (n = 495). Suicides were considered official by the Medical Mortality Registry after detailed investigative review and confirmation by the Armed Forces Institute of Pathology. Control subjects were randomly selected from the same population by the AFHSC. Controls were matched by age (+/− six months), sex, and rank. In the military, rank reflects education, income and other socioeconomic factors. The controls were also matched for blood serum drawn within 12 months of the serum draw of their matched case to minimize variability due to temporal changes in the military environment. This is a subset of a previously described population
This study was approved by the institutional review board of The Uniformed Services University (FWA00001628; DOD assurance P60001) May 8, 2009, human subjects research protocol HU873B-01. All archived data and blood serum were re-coded to eliminate personally identifiable information before release to the investigators. Because of the importance of preserving the anonymity of the individuals who died by suicide and therefore could not provide consent, special care was taken to eliminate any details of the suicide which might allow identification.
Serum sample levels of 25(OH)D, a principal storage form of vitamin D, were determined by enzyme immunoassay (Immunodiagnostic Systems Inc, Fountain Hills, AZ), with a sensitivity of 2 ng/mL and intra- and interassay coefficients of variation of 5.3% and 4.6%, respectively.
Baseline characteristics of the suicide cases and controls were analyzed with descriptive statistics and are reported in
Characteristic | Suicide Cases (n = 495) | Controls (n = 495) |
25-hydroxyvitamin D |
24.5 (0.5) | 24.8 (0.5) |
Season of blood draw (number of subjects) |
||
December/January | 64 | 86 |
February/March | 103 | 79 |
April/May | 79 | 88 |
June/July | 85 | 82 |
August/September | 73 | 72 |
October/November | 91 | 88 |
Sex | ||
Males | 467 | 467 |
Females | 19 | 19 |
Age at Suicide (SEM), yr | 28.5 (0.3) | |
Ethnicity | ||
Asian/Pacific Islander | 24 | 21 |
Black | 63 | 79 |
Hispanic | 54 | 62 |
Native American | 12 | 4 |
White | 326 | 314 |
Other/Unknown | 16 | 15 |
Branch of Service | ||
Army | 249 | 238 |
Air Force | 92 | 96 |
Marine Corps | 69 | 86 |
Navy | 85 | 75 |
Grade | ||
Enlisted | 454 | 454 |
Commissioned Officer | 36 | 36 |
Warrant Officer | 5 | 5 |
Months Deployed |
9.6 (0.3) | 11.0 (0.3) |
History of Depressive Diagnosis |
109 | 67 |
To convert to nanomoles per liter, multiply by 2.496.
There was no significant difference between suicide cases and matched controls in 25(OH)D levels, either not adjusted for season of blood sample collection (t494 = 0.41, p = 0.68), or adjusted for season of blood sample collection using a waveform algorithm (t494 = 0.43, p = 0.67).
Only bimonthly categories were available for season of blood draw, as the dates of both blood collection and of suicide were provided from AFHSC in two month intervals to preserve anonymity of the suicide casualties.
Significant difference between suicide cases and matched controls based on a paired t-test (t494 = 3.68, p = 0.0003).
Significant difference in frequency between cases and matched controls (X2 = 12.2, p = 0.0005).
Parameter | No. Cases/ Controls | DF | Estimate | Standard Error | Wald Chi-Square | p value | Odds Ratio (95% Conf. Limits) |
Vitamin D Octile 1 |
84/61 | reference | |||||
Vitamin D Octile 2 | 58/62 | 1 | −0.71 | 0.28 | 6.25 | 0.01 | 0.49 (0.28, 0.86) |
Vitamin D Octile 3 | 56/63 | 1 | −0.79 | 0.29 | 7.22 | 0.007 | 0.45 (0.26, 0.81) |
Vitamin D Octile 4 | 31/60 | 1 | −1.51 | 0.33 | 20.42 | <0.0001 | 0.22 (0.12, 0.43) |
Vitamin D Octile 5 | 55/62 | 1 | −0.80 | 0.30 | 7.19 | 0.007 | 0.45 (0.25, 0.81) |
Vitamin D Octile 6 | 85/65 | 1 | −0.32 | 0.29 | 1.25 | 0.26 | 0.73 (0.41, 1.27) |
Vitamin D Octile 7 | 67/59 | 1 | −0.56 | 0.29 | 3.73 | 0.05 | 0.57 (0.32, 1.01) |
Vitamin D Octile 8 | 59/63 | 1 | −0.73 | 0.30 | 5.81 | 0.02 | 0.48 (0.27, 0.87) |
Ethnicity |
1 | −0.58 | 0.23 | 6.43 | 0.01 | 0.56 (0.36, 0.88) | |
Months Deployed | 1 | −0.04 | 0.01 | 12.55 | 0.0004 | 0.96 (0.94, 0.98) | |
Depression Diagnosis | 109/67 | 1 | 0.69 | 0.18 | 14.16 | 0.0002 | 1.98 (1.39, 2.84) |
Octiles were calculated from waveform adjusted 25(OH)D levels based on the distribution of the control subjects. Cutoff 25-hydroxyvitamin D values were as follows. octile 1: ≤15.5; octile 2: 15.6–18.8; octile 3: 18.9–21.2; octile 4: 21.3–22.9; octile 5: 23.0–25.4; octile 6: 25.5–29.2; octile 7: 29.3–36.0; octile 8: >36.0.
Odds ratio based on the comparison of African American vs. Non-African American.
Because we postulated that optimal brain function might require a threshold level of 25(OH)D, we used conditional logistic regression analyses to estimate the association between octiles of 25(OH)D concentrations and risk for suicide. Preliminary analyses were conducted to evaluate the potential contribution of a number of covariates to the regression model, including baseline characteristics (sex, ethnicity, branch of service, rank, number of months deployed), history of a depressive diagnosis, and items from the DD 2796 form. Because DD2796 items were only available for 300 of the 495 suicide cases, we first evaluated the potential contribution of these variables in this subsample of cases and their controls. The items evaluated included questions related to experiences during deployment (i.e., danger of being killed, witnessing death, or engaged in direct combat) and questions related to mental health in the month preceding completion of the form (feeling detached, down, or depressed, having thoughts about hurting oneself, feeling little interest, feeling loss of control, experiencing nightmares, being constantly on guard, intention to seek help for mental health related problems, and receiving a referral for mental health). None of these variables were significantly related to suicide risk. Therefore, subsequent analyses were conducted using the larger sample of all cases (n = 495 with recent deployments) and their matched controls. Preliminary associations with suicide risk were found for race (African-American vs. non African American), history of depressive diagnosis (yes/no), and the number of months deployed, and thus were included as covariates in the final model used to evaluate the association of adj25(OH)D and suicide risk. Odds ratios and 95% confidence intervals were calculated based on the conditional logistic regression model, with the lowest octile (octile 1) as the reference.
Mean serum 25(OH)D concentrations (either unadjusted or adjusted for season of serum collection) did not differ between suicide cases and controls (
When controlling for season of serum collection, race (African-American vs. non African American), history of depressive diagnosis, and length of deployment, we found a statistically significant association between 25(OH)D concentrations and suicide risk, such that subjects with higher concentrations of 25(OH)D displayed a decreased risk for suicide compared to subjects in the lowest octile (
The vertical lines at each point represent the 95% confidence intervals for each odds ratio, (see
OR = 0.49 (95% C.I. 0.315–0.768).
Risk of suicide was also associated with a previous diagnosis of a depressive disorder (OR = 1.98, 95% confidence interval = 1.39 to 2.84;
Parameter | No. Cases/ Controls | DF | Estimate | Standard Error | Wald Chi-Square | P value | Odds Ratio4 (95% Conf. Limits) |
Vitamin D Octile 1 |
84/61 | reference | |||||
Vitamin D Octile 2 | 58/62 | 1 | −0.42 | 0.26 | 2.6 | 0.11 | 0.66 (0.40, 1.10) |
Vitamin D Octile 3 | 56/63 | 1 | −0.5 | 0.26 | 3.7 | 0.05 | 0.61 (0.37, 1.01) |
Vitamin D Octile 4 | 31/60 | 1 | −1.07 | 0.3 | 13.23 | 0.0003 | 0.34 (0.19, 0.61) |
Vitamin D Octile 5 | 55/62 | 1 | −0.49 | 0.26 | 3.47 | 0.07 | 0.61 (0.37, 1.03) |
Vitamin D Octile 6 | 85/65 | 1 | −0.05 | 0.25 | 0.04 | 0.85 | 0.95 (0.58, 1.56) |
Vitamin D Octile 7 | 67/59 | 1 | −0.23 | 0.25 | 0.81 | 0.37 | 0.80 (0.48, 1.31) |
Vitamin D Octile 8 | 59/63 | 1 | −0.4 | 0.26 | 2.33 | 0.13 | 0.67 (0.40, 1.12) |
Octiles were calculated from waveform adjusted 25(OH)D levels based on the distribution of the control subjects. Cutoff 25-hydroxyvitamin D values were as follows. octile 1: ≤15.5; octile 2: 15.6–18.8; octile 3: 18.9–21.2; octile 4: 21.3–22.9; octile 5: 23.0–25.4; octile 6: 25.5–29.2; octile 7: 29.3–36.0; octile 8: >36.0.
To our knowledge, this is the first study to examine the relationship between vitamin D status and suicide risk. We found that the risk for suicide was increased in the lowest octile of 25(OH)D levels, all the members of which had seasonally adjusted levels of 25(OH)D below 20 ng/mL. When the odds ratios for each octile are fitted to a decreasing exponential function (
Our results constitute one of the largest studies of vitamin D in the military. However, because we were unable to match controls and suicide cases by the exact date of blood collection, the season of blood collection was not balanced between groups; more controls had their blood drawn in the spring when 25(OH)D is lowest, and more suicide cases had their blood drawn in the fall when 25(OH)D is highest. Not surprisingly, seasonal adjustment was critical for proper analysis of our data, as 25(OH)D levels averaged the same in both groups before adjustment. The date of blood draw was unrelated to the date of suicide suggesting that the imbalance in the season of blood draw was due to chance. One limitation of our study is that 25(OH)D was not measured at the time of the suicide, but some months earlier; other studies of this population have used similar methods
Our findings that African Americans had lower levels of 25(OH)D and also lower rates of suicide is consistent with other studies
Our findings are observational in character, and hence do not establish a causal role for vitamin D deficiency and suicide. It is possible that sunlight may exert beneficial effects that are independent of vitamin D, as suggested by the fact that light therapy can reduce suicidal ideation in patients with seasonal affective disorder
Psychiatric illness is usually diagnosable retrospectively after suicides
Military service requirements for protective clothing and night time operations may reduce the opportunity for normal sunlight exposure. In a recent study, 25(OH)D levels fell in new recruits after eight weeks of combat training in South Carolina, even though it was summer
The Division of Intramural Basic and Clinical Research, NIAAA, NIH supported this study and was responsible for design and conduct of the study; collection, management, analysis, and interpretation of the data; and preparation, review, and approval of the manuscript. We are indebted to Drs. Angie Eick and Mark Rubertone, AFHSC, for data assembly and sample access and to Dr. Laura Kwako, Monte Phillips, Janet Umhau and Tricia Umhau for their editorial comments. We thank Dr. John Cannell for his insightful discussions about vitamin D.