The scale of the undertaking was considerable. Searching the Scopus database from January 1970 to December 2024, the researchers retrieved 1,965 publications using keyword combinations linking milk and dairy products with biomolecules, carnitine and betaine. After removing duplicates and incomplete records, and screening out studies that treated these compounds merely as feed additives or analytical targets, 179 papers remained for detailed analysis. The screening followed the PRISMA guidelines for systematic reviews, with two researchers independently assessing eligibility. The final corpus spanned agricultural science, biochemistry, medicine, veterinary science and pharmacology, reflecting the remarkable breadth of interest in these molecules.

The computational pipeline itself is a showcase of modern literature analysis. The team compiled the abstracts of all 179 papers into a corpus, then standardized spellings, broke the text into tokens, removed stop words and applied stemming and lemmatization. Crucially, they deliberately removed the search terms themselves, including milk, dairy, carnitine and betaine, because these words appeared in nearly every abstract and would have drowned out the meaningful thematic signal. A document-term matrix was then weighted using the term frequency-inverse document frequency method, which rewards words that are both frequent within a document and distinctive across the dataset. The result was a ranked vocabulary of the field’s core concepts.

The highest-scoring terms told a story in miniature. Metabolit, cow, infant and cholin dominated the word cloud, with scores above 2.5 on the TF-IDF scale, followed by concentration, intake, formula and food. Their prominence is no accident. Carnitine and betaine are metabolites present in both milk and dairy products, cows are the primary source of the dairy consumed worldwide, infants are the population most dependent on milk as a complete food, and choline sits at the metabolic crossroads, sharing one-carbon and methyl-group transfer pathways with both carnitine and betaine. The words essentially trace the biological chain from rumen to cradle.

Topic analysis using Latent Dirichlet Allocation, a statistical model that uncovers hidden thematic structures in large text collections, sorted the corpus into three distinct research themes of almost equal size. The largest, covering 35 percent of papers, concerns carnitine and betaine in early-life nutrition, from breast milk to infant metabolomics. A second theme, at 33 percent, frames dairy bioactives as nutraceuticals for adult chronic disease, spanning cardiometabolic protection to anticancer activity. The third, at 32 percent, addresses metabolic regulation in ruminants and how feeding strategies shape the milk metabolome. Publication trends over time showed the ruminant and infant themes still growing exponentially, while the nutraceutical theme has slowed somewhat since its earlier surge.

The ruminant theme reveals carnitine and betaine as sensitive biomarkers of energy balance in dairy animals. L-carnitine, synthesized from the amino acids lysine and methionine, is indispensable for shuttling long-chain fatty acids into mitochondria for beta-oxidation, the process that generates cellular energy. When high-producing cows enter negative energy balance, this transport system becomes a bottleneck, leading to accumulation of toxic acyl-CoA intermediates and potentially fatty liver and ketosis. Betaine, meanwhile, acts as an organic osmolyte and a methyl donor, regenerating methionine and supporting cellular volume regulation under metabolic stress. Studies comparing pasture with total mixed rations, and green forage with conventional diets in buffalo, showed that these metabolites respond dynamically to changes in rumen fermentation and systemic stress, making them integrative markers of metabolic resilience rather than passive compositional traits.

The infant nutrition theme highlights a striking biological fact: newborns and young infants have limited capacity to synthesize carnitine themselves, making milk their critical exogenous source. Clinical observations in carnitine-deficient infants documented impaired fatty acid oxidation, hypoglycaemia and disrupted energy homeostasis, establishing carnitine as a conditionally essential nutrient during early development. Studies comparing breast-fed and formula-fed infants found that formulas were often deficient or variable in carnitine, prompting fortification strategies, although fortification may not fully replicate the complex metabolite matrix of human milk. Maternal diet, including dairy, meat, eggs and fish, influences the choline, betaine and carnitine content of human milk, though inter-individual variability is considerable and shaped by genetics, lifestyle and lactation physiology.

Perhaps the most provocative thread running through the review is the so-called TMAO paradox. Gut bacteria convert dietary carnitine, choline and betaine into trimethylamine, which the liver then oxidizes to trimethylamine N-oxide, a compound associated in several studies with atherosclerosis, vascular inflammation and thrombotic risk. The paradox is that the very molecules indispensable in infancy are implicated as substrates in potentially harmful pathways in adults. Yet the evidence is not one-sided. Recent work found that lower plasma levels of 5-aminovaleric acid betaine are associated with increased risk of type 2 diabetes, and a study spanning children and adults found no association between plasma TMAO and adverse cardiometabolic outcomes in the healthy general population. The review concludes that life stage, food matrix and gut microbiota composition all modulate the risk-benefit balance of these trimethylated compounds.

The adult health theme offers a counter-narrative to the simplistic view that all trimethylated compounds from animal foods are harmful. Delta-valerobetaine, a betaine derivative originating from rumen microbial metabolism, accumulates in ruminant milk and dairy products, and laboratory studies show that delta-valerobetaine-rich dairy fractions protect endothelial cells by reducing oxidative stress, improving mitochondrial function and preserving nitric oxide bioavailability. In colon cancer models, delta-valerobetaine and related betaines inhibit tumour cell growth while sparing healthy cells, an effect linked to sirtuin-dependent metabolic reprogramming. Preclinical research on delactosed buffalo milk whey has shown chemopreventive effects in mouse models of colorectal cancer, reducing precancerous lesions and restoring a healthier gut microbiota, while also triggering apoptotic and necroptotic cell death pathways in tumour tissue. Whey, often dismissed as a by-product, emerges as a concentrated source of nutraceutical molecules.

The review’s authors acknowledge limitations, including reliance on a single database, English-language publications only, and the exclusion of grey literature, which may introduce geographic and language bias. Nevertheless, their integrated perspective delineates a mechanistic continuum from feed and rumen microbiota through the milk metabolome to early-life programming and, ultimately, chronic disease risk or protection in adults. The practical implications are twofold: feeding strategies in dairy production could be tuned to enrich milk in beneficial bioactives, and next-generation functional dairy products could be designed with targeted health-promoting properties. Future research, the authors argue, should focus on longitudinal and intervention studies to establish how processing, species-specific milk composition and the gut microbiota shape the bioavailability and biological effects of carnitine, betaine and their derivatives, knowledge essential for evidence-based nutritional recommendations in both animal and human health.

Subject of Research: Carnitine and betaine bioactives in milk and dairy products and their roles in animal metabolism, infant nutrition and human health

Article Title: Important bioactives carnitine and betaine in milk and dairy products: a systematic review based on text mining and topic analysis

Article References: Trapanese, L., Salzano, A., Cacciola, N. A., Neglia, G., Bifulco, G., Balestrieri, M., D´Occhio, M. J., & Campanile, G. (2026). Important bioactives carnitine and betaine in milk and dairy products: a systematic review based on text mining and topic analysis. Food Science of Animal Resources, 46(1), Article 108. https://doi.org/10.1007/s44463-026-00112-6

Image Credits: AI Generated

DOI: 10.1007/s44463-026-00112-6

Keywords: carnitine, betaine, milk, dairy products, text mining, topic analysis, TMAO, infant nutrition, nutraceuticals, ruminant metabolism, milk metabolome, delta-valerobetaine