In a recent study published in Nutrients, researchers performed a randomized clinical trial (RCT) to investigate the effectiveness of curcumin in lowering depression among obese individuals with diabetes mellitus type 2 (T2DM).

Study: Curcumin Reduces Depression in Obese Patients with Type 2 Diabetes: A Randomized Controlled Trial. Image Credit: Moving Moment/Shutterstock.com

Background

T2DM is a chronic illness characterized by high blood glucose levels caused by pancreatic beta-cell dysfunction and reduced insulin action. It is a global public health concern with increasing incidence in wealthy countries.

T2DM patients are more likely to become disabled, incapacitated, or unemployed. T2DM also raises the likelihood of developing major depressive disorder (MDD), which causes functional impairment and necessitates treatment.

T2DM and depression coexist in a bidirectional manner, with those afflicted facing disability-related job loss, noncompliance with medical treatment, and increased mortality risks.

Antidepressants, the principal therapy for MDD, can cause weight gain and poor cardiometabolic health. Curcumin, the major curcuminoid in turmeric, may reduce anxiety and depression; however, there is limited relevant RCT evidence.

About the study

In the present double-blinded and placebo-controlled RCT, researchers evaluated the depression-lowering effects of curcumin among 227 obese individuals with T2DM, emphasizing elevated serotonin levels due to antioxidant and anti-inflammatory properties.

The researchers included individuals aged 35 years and above who received a T2DM diagnosis within the previous year, had body mass index (BMI) values of ≥23 kg/m2, hemoglobin A1c (HbA1c) below 6.50%, and fasting blood glucose below 110 mg per dL. They ascertained diabetes diagnosis using the 2017 American Diabetes Association (ADA) criteria.

The study excluded individuals with type 1 diabetes, metabolic syndrome, glucose tolerance impairment, maturity-onset diabetes of the young (MODY), dyslipidemia, gestational diabetes, severe hypertension, and those taking insulin injections or antidiabetic medicines apart from metformin.

To evaluate dietary quality and physical exercise levels, study participants completed three-day diet records and a diet questionnaire at study initiation and after 12 weeks.

Researchers randomized participants to receive ethanol-extracted curcumin (intervention group) or a placebo (control group).

Participants consumed three curcumin (or the placebo drug) capsules twice daily for a year, each capsule containing 250 milligrams of curcuminoids. All participants followed standard diet and exercise protocols three months before randomization.

The researchers assessed depression, the primary study outcome, using the Patient Health Questionnaire-9 (PHQ-9). They withdrew participant blood to measure biomarkers at baseline and three months, six months, nine months, and one year.

Biomarker assessment included serotonin, inflammatory cytokines [such as interleukin-1 beta (IL-1β), IL-6, tumor necrosis factor-alpha (TNF-α), antioxidants [glutathione peroxidase activity (RANSEL), superoxide dismutase activity (RANSOD), and total antioxidant status (TAS)], and malondialdehyde.

The researchers performed enzyme-linked immunosorbent assays (ELISA) to evaluate serum serotonin levels and Homeostatic Model Assessment of Insulin Resistance (HOMA-IR) to assess insulin resistance.

They assessed levels of creatinine (≥1.20 mg/dL), alanine transaminase (ALT), and aspartate transaminase (AST) levels (≥3.0 times above the normal range for both) to assess the adverse effects of curcumin.

They also recorded patient symptoms. They compared continuous variables using student t-tests and categorical variables using chi-square tests and followed the intention-to-treat approach to assess outcome variables.

Results

At one year, curcumin consumers showed significantly lowered depression severity, as indicated by a 20% improvement in PHQ-9 scores (compared to 2.6% among controls), with elevated serotonin and lower IL-1β, IL-6, and TNF-α levels compared to placebo recipients. The anti-inflammatory properties of curcumin extracts may elevate serum serotonin levels.

RANSEL, RANSOD, and TAS were enhanced among curcumin consumers, whereas the placebo group showed higher MDA (a biomarker of oxidative stress).

In addition, HbA1c and fasting blood glucose levels were significantly lower among intervention recipients compared to controls at six months, nine months, and one year.

Compared to placebo recipients, those receiving the study intervention showed significantly decreased HOMA-IR levels at each follow-up assessment.

Mean BMI and body weight were also significantly lower among curcumin consumers compared to controls across follow-up, a considerable advantage over conventional antidepressants.

The participants reported mild adverse effects such as headache, abdominal pain, and diarrhea without significant differences in creatinine, AST, and ALT levels among the groups and no hypoglycemic event following curcumin use. The findings indicate that curcumin extracts are safe to use for ≥12 months.

Conclusion

The study found curcumin effective and safe for lowering depression severity in obese individuals with T2DM.

Curcumin may help alleviate depression by raising serotonin levels, reducing inflammation, and decreasing oxidative stress.

However, further research is needed better to understand the processes behind curcumin’s benefits for obesity and establish dose-response relationships. Future studies should involve more diverse populations to increase the generalizability of the study findings.