How Malnutrition and Thyroid Hormones May Shape Tuberculosis Risk Through the Endocrine-Immune Axis

Tuberculosis still infects roughly 10.6 million people each year, and despite decades of prevention and control efforts it remains one of the leading infectious causes of death worldwide. While exposure to Mycobacterium tuberculosis is a prerequisite for infection, whether an exposed person actually develops active disease depends heavily on host factors: nutritional status, immune competence, comorbid conditions, and socioeconomic determinants. A new review published in Frontiers in Tuberculosis by researchers at Western University of Health Sciences argues that two of these factors—nutrition and thyroid function—may be far more entangled with tuberculosis risk than is generally appreciated, and that their interaction could form a self-perpetuating cycle that weakens the body’s defenses against the bacterium.

The review, led by Nooneh Khachatourian, Rubina Takhmazian, and Vishwanath Venketaraman, builds on a well-established epidemiological foundation. Undernutrition is already recognized as one of the most significant modifiable risk factors for tuberculosis, with more than one-fifth of global TB cases estimated to be attributable to it. Systematic reviews have shown that undernutrition substantially increases the risk of developing active TB and that malnutrition is associated with worse treatment outcomes, including treatment failure, loss to follow-up, and death. But the relationship runs both ways: TB itself drives nutritional deterioration through chronic inflammation, increased metabolic demands, reduced appetite, and impaired nutrient utilization. What the authors add to this picture is a third player—the thyroid gland—whose hormone output depends critically on the very micronutrients that malnutrition depletes and whose hormones, in turn, help regulate the immune cells that fight M. tuberculosis.

Thyroid hormones, triiodothyronine (T3) and thyroxine (T4), are best known for regulating metabolism, energy expenditure, lipid profiles, glucose utilization, thermogenesis, and body weight. But an accumulating body of experimental evidence shows that they also act directly on the immune system. Macrophages, dendritic cells, neutrophils, and T lymphocytes all express thyroid hormone receptors and respond to thyroid hormone signaling. Experimental studies indicate that these hormones regulate neutrophil respiratory burst activity, reactive oxygen species production, macrophage phagocytic capacity, cytokine signaling, and inflammatory responses. Thyroid hormone receptor α signaling has also been implicated in T-cell activation and in the function of regulatory T cells, which temper pro-inflammatory responses and enhance anti-inflammatory regulation. Because many of these same pathways are central to controlling intracellular pathogens such as M. tuberculosis, the authors propose that hypothyroidism—an extremely common endocrine disorder worldwide—may represent an underrecognized factor compromising antimicrobial defense.

The bridge between nutrition and thyroid function is built from specific micronutrients. Iodine is the structural backbone of both T3 and T4; the body cannot synthesize it, so dietary intake is indispensable. Although iodization programs have reduced severe deficiency, roughly 30 percent of the world’s population remains at risk of inadequate iodine intake, which impairs hormone synthesis and leads to compensatory thyroid enlargement and hypothyroidism. Selenium is equally critical: the thyroid contains the highest concentration of selenium per gram of tissue of any organ in the human body, reflecting the role of selenium-dependent iodothyronine deiodinases (DIO1, DIO2, and DIO3) that convert the prohormone T4 into biologically active T3. Selenium-dependent glutathione peroxidases and thioredoxin reductases also protect thyroid tissue from the oxidative damage generated during hormone biosynthesis, a process that inherently requires hydrogen peroxide as a substrate for thyroid peroxidase-mediated iodination. Selenium deficiency therefore impairs hormone activation, increases oxidative stress, and is associated with autoimmune thyroid disease.

Iron, the most prevalent micronutrient deficiency worldwide, adds another layer. Thyroid peroxidase, the enzyme responsible for iodide oxidation and organification, is heme-dependent and requires adequate iron availability for optimal catalytic activity. A recent systematic review and meta-analysis found significantly lower free T3 and free T4 concentrations among iron-deficient individuals compared with healthy controls. Iron deficiency frequently coexists with chronic inflammation, malnutrition, and infectious disease, which the authors suggest makes its impact on thyroid physiology particularly relevant in populations at elevated TB risk. Zinc contributes through zinc-finger transcription factors and thyroid hormone receptor signaling, with deficiency linked to impaired hormone metabolism and immune dysfunction. Vitamin D, meanwhile, exerts immunomodulatory effects through regulation of T-cell differentiation, cytokine production, and immune tolerance, and observational studies consistently report lower circulating vitamin D concentrations in patients with hypothyroidism, Hashimoto’s thyroiditis, and autoimmune thyroid disease compared with healthy controls.

The immunological case for why thyroid dysfunction might matter in TB rests on the biology of host defense. After inhalation, resident alveolar macrophages constitute the first line of defense, and successful containment of M. tuberculosis requires efficient macrophage activation, granuloma formation, robust T-cell responses, tightly regulated cytokine networks, and control of oxidative stress. Experimental studies show that thyroid hormones regulate macrophage survival and phagocytic activity, influence the production of reactive oxygen species, and modulate the expression of genes involved in antimicrobial responses. On the adaptive side, control of M. tuberculosis depends largely on CD4-positive T lymphocytes generating type 1 helper (Th1) responses characterized by interferon-γ and tumor necrosis factor-α—cytokines that activate infected macrophages and maintain granulomas. Thyroid hormones influence T-cell development, differentiation, and activation through receptor-mediated signaling, so dysregulation of these pathways could plausibly weaken the Th1 response that keeps mycobacteria in check.

Evidence from autoimmune thyroid disease reinforces how closely thyroid function and immune regulation are intertwined. Conditions such as Hashimoto’s thyroiditis and Graves’ disease feature lymphocytic infiltration, loss of immune tolerance, abnormal helper T-cell responses, and chronic cytokine-mediated inflammation, with increased expression of the chemokines CXCL9, CXCL10, and CXCL11 recruiting Th1 lymphocytes into thyroid tissue. Impaired suppressive activity of regulatory T cells has also been reported in autoimmune thyroid disease, and because balanced Treg responses are important for limiting immunopathology during TB infection, such disturbances may further influence susceptibility and disease progression. Beyond direct immune effects, chronic hypothyroidism is associated with low-grade systemic inflammation and altered immune cell metabolism, and thyroid hormones regulate the mitochondrial function, glucose utilization, and lipid metabolism that underpin the energetic demands of immune activation—processes increasingly recognized as determinants of TB outcomes.

The epidemiological spark for this framework comes from an 18-year nationwide population-based longitudinal cohort study, which found that individuals with hypothyroidism had an increased risk of subsequently developing TB, while patients with TB also had an elevated risk of subsequent hypothyroidism. The authors are careful to note that this observational association cannot establish causality and may be confounded by nutritional status, comorbidities, socioeconomic conditions, chronic inflammation, and medication exposure. The relationship is also bidirectional in a treatment context: antitubercular agents including ethionamide, prothionamide, and para-aminosalicylic acid inhibit thyroid peroxidase activity and disrupt iodine organification, producing hypothyroidism in approximately 17 percent of patients receiving treatment for multidrug-resistant TB. Chronic infection itself alters hypothalamic-pituitary-thyroid axis regulation through pro-inflammatory cytokines such as IL-1, IL-6, and TNF-α, meaning TB can both cause and be influenced by endocrine disturbance.

On the intervention side, the review takes a notably sober view of supplementation. Vitamin D is the most extensively studied micronutrient in the TB context because it enhances macrophage antimicrobial activity through induction of cathelicidin, stimulation of autophagy, and promotion of intracellular killing of M. tuberculosis. Yet recent randomized-trial meta-analyses have found no significant reduction in TB infection or progression to active disease with vitamin D supplementation, and limited or inconsistent effects on microbiological treatment outcomes such as sputum smear and culture conversion. The authors argue that evidence supporting correction of a documented deficiency should be distinguished from evidence supporting routine supplementation specifically for TB prevention, and they point to substantial heterogeneity across studies in baseline nutritional status, dose, formulation, duration, and clinical outcomes as a key reason findings have been inconsistent. Similar caution applies to selenium, zinc, and iron: correcting documented deficiencies may support both thyroid and immune function, but evidence that supplementation independently improves TB-specific outcomes remains limited, and excessive intake of certain micronutrients can itself harm endocrine or immune function.

One of the more intriguing therapeutic leads involves glutathione, the body’s principal intracellular antioxidant. Patients with TB frequently exhibit depleted glutathione levels, compromising antioxidant defenses, macrophage function, cytokine regulation, and T-cell-mediated immunity. Experimental and clinical studies suggest that glutathione supplementation may reduce oxidative stress, enhance Th1-associated immune responses, increase production of IFN-γ and TNF-α, and decrease intracellular mycobacterial burden—preliminary but biologically coherent findings, given that glutathione metabolism is closely linked to selenium-dependent antioxidant systems. The authors conclude that the nutritional–endocrine–immune framework they propose is biologically plausible and hypothesis-generating rather than an established causal pathway, and that current evidence does not support routine thyroid screening solely to reduce TB risk. What they call for instead are prospective cohort studies determining whether thyroid dysfunction independently predicts TB after accounting for confounders, adequately powered trials of micronutrient correction in deficient populations, and standardized assessment of nutritional status, thyroid function, and clinical outcomes. If the proposed cycle of malnutrition, thyroid dysfunction, and impaired antimycobacterial immunity holds up under clinical scrutiny, nutritional optimization and early endocrine management could eventually become integrated adjunctive strategies in the fight against one of humanity’s oldest infectious diseases.

Subject of Research: The interplay between nutrition, thyroid function, and immune defense against tuberculosis

Article Title: Nutrition, thyroid function, and tuberculosis: exploring the endocrine–immune axis

Article References: Khachatourian, N., Takhmazian, R., & Venketaraman, V. (2026). Nutrition, thyroid function, and tuberculosis: exploring the endocrine–immune axis. Frontiers in Tuberculosis, 4, Article 1945832. https://doi.org/10.3389/ftubr.2026.1945832

Image Credits: AI Generated

DOI: 10.3389/ftubr.2026.1945832

Keywords: tuberculosis, thyroid hormones, hypothyroidism, micronutrients, iodine, selenium, vitamin D, immune regulation, malnutrition, endocrine-immune axis, glutathione, Mycobacterium tuberculosis