The goal of this randomized controlled trial is to evaluate the early bactericidal activity, early inflammatory response, and safety of omega-3 long chain polyunsaturated fatty acid (n-3 PUFA) supplementation in adult patients (aged 18- 45 years) with newly diagnosed, bacteriologically confirmed drug-sensitive pulmonary tuberculosis.

The main questions it aims to answers are:

• Does adjunct n-3 LCPUFA supplementation reduce the sputum culture time to positivity
• Does it improve inflammatory markers and TB treatment outcomes compared to placebo Researchers will compare daily supplementation with ~2g n-3 LCPUFA (EPA and DHA ) to placebo (high linoleic sunflower oil) to determine effects on bactericidal activity, inflammation, and clinical outcomes.

Participants will:

• Be randomly assigned to receive either n-3 LCPUFA or Placebo daily for 8 weeks with the intensive phase of TB treatment
• Attend clinical visit baseline, and follow up visit mostly weekly for 2 months and then monthly for 4 months of the continuous phase of TB treatment
• Provide blood, sputum and urine samples for biomarkers and metabolomic analysis
• Undergo assessments of iron status, body composition and muscle strength

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.

beginning one year and ending 3 years after publication date

research who has a methodological sound proposal that has been approved by an independent review committee identified for this purpose