The Story of Essential Amino Acid

A recent study led by researchers at UCLA and published revealed that the breast milk of mothers living with HIV/AIDS contains markedly lower concentrations of the essential amino acid tryptophan, an amino acid known to support infant immune function, growth, and neural development.

Globally, about 1.3 million children are born each year to women with HIV. Even though antiretroviral therapy (ART) effectively prevents the virus from transmitting to the child, these HIV-exposed but uninfected children still bear a roughly 50 % greater risk of death in low-income settings, along with higher rates of infections, growth faltering, and neurocognitive issues.¹ Before ART became widely available, mortality among this group was two- to three-fold higher than for infants born to HIV-negative mothers. The underlying causes of this persistent vulnerability have remained unclear.

In the study, researchers analysed 1,426 breast-milk samples from 326 Zambian women (288 living with HIV and 38 HIV-negative) collected across 18 months postpartum; they measured more than 800 metabolites using advanced metabolomic profiling, and then replicated key findings in a secondary cohort of 47 women from Haiti who were on ART.

Findings showed that mothers living with HIV had breast-milk tryptophan levels approximately 50 % lower than those of HIV-negative mothers throughout the entire 18-month period.² Simultaneously, the kynurenine-to-tryptophan ratio, a marker of immune activation, was consistently elevated. Further, maternal plasma tryptophan was also reduced, indicating that the deficit in milk reflects systemic depletion rather than only problems transferring tryptophan into milk.

The researchers also discovered elevated amounts of an antiviral molecule known as ddhC,³ as well as increased cytosine and dimethylarginine in the milk of HIV-positive mothers. These metabolic markers suggest chronic inflammation and prolonged interferon activation. These signatures remained evident even in the ART-treated Haitian cohort, underscoring that the metabolic disturbance persists despite modern therapy.

These results provide the first metabolic explanation for why HIV-exposed but uninfected children continue to face health challenges. They suggest that tryptophan deficiency and altered metabolism may represent a shared mechanism linking immune, growth, and neurocognitive risks in this population.

However, the authors emphasize that nutritional intervention should be approached with caution. Because HIV‐associated inflammation shunts tryptophan into downstream pathways that may produce neurotoxic metabolites, simply supplementing tryptophan without modulating these pathways could be harmful. Further research, including animal studies, is planned to define safe and effective strategies to protect these children.

References:

1. Prendergast, A. J. & Evans, C. Children who are HIV-exposed and uninfected: evidence for action. AIDS 37, 205–215 (2023).
   
   
2. Altered milk tryptophan and tryptophan metabolites in women living with HIV, Nature Communications (2025). DOI: 10.1038/s41467-025-64566-w
   
   
3. Gizzi, A. S. et al. A naturally occurring antiviral ribonucleotide encoded by the human genome. Nature 558, 610–614 (2018).