Wellness Check: Nutrition

Prescription of folic acid supplementation was associated with reduced suicidal behavior

1. In patients with prescription for folic acid, rate of suicidal behavior was lower in months with prescription compared to months without.

2. Furthermore, amongst patients with prescriptions for vitamin D12, rates of suicidal behavior did not differ between months with or without prescription.

Evidence Rating Level: 2 (Good)

Suicide is a leading cause of death in the United States (US), with increasing incidences particularly during the COVID-19 pandemic. Therefore, additional therapeutic options that may modulate suicidal behavior are needed. Folic acid levels have been associated with depression and suicidality in small case-control studies. Furthermore, folic acid supplementation has been shown to augment therapy for patients with depression. However, whether folic acid supplementation alone can modulate suicidal behavior has not been well characterized.

This study was a within-person exposure-only cohort study design using insurance claims data from 866 586 (81.3% female) adult patients in the US. Patients aged 18 years or older with private health insurance were included in the study. The exposure was folic acid supplementation as measured by having a folic acid prescription. The negative control group was patients exposed to cyanocobalamin (vitamin B₁₂). The primary outcome was rate of intentional self-harm captured using diagnoses codes for suicide attempts, depression, anxiety, bipolar, schizophrenia, sleep disorders, and pain.

The study results demonstrated that there were fewer suicidal events during months covered by folic acid prescription compared to months without (4.73 vs. 10.61 per 100,000 person-months). In contrast, there were no differences in suicidal event rate between months with vitamin B₁₂ prescription and months without. However, this study was limited as it found that many patients prescribed folic acid had a pain disorder or were taking folate-reducing agents, which limits the generalizability of these results. Nonetheless, these results warrant further study of possible mechanisms of action underpinning the association between folic acid and suicidal behavioral, as well as randomized control studies to test whether the association is due to a causative relationship.

Eating only during the day protected against mood vulnerability during circadian disturbances

1. In this study, participants eating both during the day and night had increased depression and anxiety-like mood levels during simulated night work.

2. Furthermore, a higher degree of misalignment between circadian and behavior cycles was associated with increased depression and anxiety-like mood levels during simulated night work.

Evidence Rating Level: 2 (Good)

Shift, or overnight workers, account for a significant portion of the United States (US) workforce and serve in many essential services. Shift workers often experience misalignment between their circadian rhythm and environmental/behavioral cycles, which has been associated with higher risk of depression and anxiety. However, whether modulating certain behavioral cycles, such as eating, may modify mood vulnerabilities has not been well tested.

This was a parallel-design randomized control trial of 19 healthy, adult participants (12 men). Participants with history of depressive/anxiety-related disorders, smoking, and on any medications were excluded. Patients were randomized to either a daytime and nighttime meal control group or daytime only meal intervention group.  Simulation of night work was achieved by having participants in dim light for four 28-hour “days”, so that by the fourth day, their behavioral cycles were inverted by 12 hours. The primary outcome was depression and anxiety-like mood levels, which were assessed every hour using computerized visual analogue scales (VAS).

This study found that compared to baseline (day 1), patients with daytime and nighttime eating had increased depression- and anxiety-like mood levels (26.2% and 16.1% increase, respectively) during the simulated night shift (day 4), while the daytime eating only meal intervention group did not. However, this study was limited in its generalizability due to the small, restrictive, and homogenous patient population, as well as the short observational period. Nonetheless, the study design accounted for many potential behavioral confounders, and therefore, offers evidence toward the potential benefit of mealtime behavioral modifications that warrant further study.

Vitamin D3 and omega-3 fatty acid supplementation does not protect against frailty

1. In this study, vitamin D3 and omega-3 fatty acid supplementation in heathy, older adults without vitamin D3 deficiency did not prevent changes in frailty over time.

2. Furthermore, older participants had greater increase in frailty over time.

Evidence Rating Level: 1 (Excellent) 

Frailty is a syndrome of decreased physiologic reserve and is experienced by up to half of adults 85 years or older. As the aging population increases in the world, identifying ways to combat frailty is essential. The Mediterranean diet has been shown to reduce frailty. However, whether taking supplements of vitamin D₃ and omega-3 fatty acid, which are abundant in the Mediterranean diet, would have similar benefits is not well known.

This study was ancillary to a randomized control trial of 25,057 men (over the age of 50) and women (over the age of 55) across all 50 states of the United States of America. Patients with cancer or cardiovascular diseases were excluded. Patients were randomized to receive daily supplementation with either vitamin D₃ + omega-3 fatty acid, vitamin D₃ alone, omega-3 fatty acid alone, or 2 placebos for 5 years. The primary outcome was change in frailty score over time, which was measured via annual Rockwood frailty index assessing function, cognition, mood, and comorbidities.

Study results demonstrated that neither vitamin D₃ nor omega-3 fatty acid supplementation modified change in frailty score compared to placebo. Controlling for sex, baseline age, or other randomized intervention did not change results. Furthermore, incident frailty was similar between the two groups throughout the duration of the study period. However, this study was limited by several confounders. First, most participants were not vitamin D₃ deficient and regularly consumed fish, which may mask the effect of subsequent supplementation. Second, the mean frailty score was lower in the study population than the general population, which may limit the generalizability of these results. Nonetheless, these results suggest that supplements alone should not be a therapeutic strategy for preventing frailty.

Image: PD

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