Effects of Adjunct Omega-3 Long Chain Polyunsaturated Fatty Acids in Pulmonary Tuberculosis Patient: an Early Bactericidal Activity and Inflammatory Trial

Anti-inflammatory omega-3 long-chain polyunsaturated fatty acids (n-3 LCPUFA) supplementation results in improvement of infectious respiratory conditions, yet little evidence in patients with pulmonary tuberculosis (TB) exists. Animal studies have shown that adjunct n-3 LCPUFA optimized treatment outcomes by resolving inflammation, improving immune response, and mitigating iron deficiency and anaemia of inflammation.

This randomized controlled early bactericidal activity (EBA), early inflammatory activity (EIA), and safety trial among patients with newly bacteriologically confirmed adult drug-sensitive pulmonary TB patients (DS-TB), aged 18 - 45 years (n = 40), will investigate the clinical and anti-inflammatory effects of n-3 LCPUFA adjunct treatment for two months.

Patients presenting at Tshepong Hospital, Klerksdorp, North West Province, will receive either ~2 g n-3 LCPUFA (eicosapentaenoic acid (EPA) plus docosahexaenoic acid (DHA)) or placebo (high-linoleic sunflower oil) daily for two months. The primary outcome is sputum culture time to positivity. Secondary outcomes include time to stable culture conversion, proportion of participants converted at 8 weeks, inflammatory markers and safety. Exploratory objectives include iron status, body composition and muscle strength, clinical outcomes, microbial translocation biomarkers, resting energy expenditure, fatty acid composition, plasma lipid mediators, and related metabolomics and gene expression.

Inclusion criteria

• adults aged 18-45 years
• laboratory confirmed Pulmonary TB defined as a hard copy of a sputum result detected by WHO recommended assay or mycobacteria culture.
• Women of childbearing potential with a negative pregnancy test on enrollment
• All participant irrespective of HIV status who consent to have a HIV test during enrollment.

Exclusion criteria

• Comorbid condition with treatment of NSAIDS is indicated
• Institutionalized or incarcerated individuals
• Those on Multiple drug resistance treatment for more than 4 days within the past 6 months or within 1 month to prior to TB treatment initiation
• Pregnant or breastfeeding women or women who become pregnant in the first 4 weeks of the trial will be withdrawn
• show lab safety values: AST or ALT > x3 upper limit of normal (ULN) or Total bilirubin > 2x the ULN, Neutrophils ≤ 700/mm³, Platelets < 50,000/mm³, Haemoglobin < 8 g/dL, Serum creatinine > 2× ULN.
• Are receiving or planning treatment with any of the following in the 3 months before or during the trial:

Anticoagulants Immune-modulating therapy (e.g., cancer treatment, oral/inhaled corticosteroids) Antacids or proton pump inhibitors (PPIs)

• Have a known allergy or sensitivity to fish or fish oil.
• Have a recent history (within 2 years) or current clinical evidence of:

Peptic ulcer disease or GI bleeding Coagulopathy or bleeding disorders Kidney or liver disease requiring hospitalisation Cardiovascular disease or significant risk factors for it

-Are HIV-positive and meet any of the following: CD4 count < 100 cells/mm³ Viral load > 400 copies/mL (if on ART) Not yet on ART but are expected to initiate treatment during the 8-week intervention phase

• Report high-risk alcohol use (average >4 units/day or binge drinking patterns)
• Have any other medical condition or situation that, in the investigator's opinion, may interfere with protocol adherence or data interpretation.
• Plan to relocate from the study area within the next 3 months.
• Are currently using omega-3 or omega-6 supplements and are unwilling to stop for the duration of the study.