Cancer is a multifactorial disease with a high incidence and prevalence worldwide. The World Health Organization (WHO) estimates that one-third of cancer deaths are due to modifiable factors, including an unhealthy lifestyle. This has led the scientific community to show increasing interest in studies focused on discovering the potential benefits of certain foods, such as kefir, a fermented dairy product that is easily accessible and widely consumed by the population. The quality guarantees offered by the dairy industry make its consumption safe, which, combined with its low cost, makes it a promising food in the field of research. Therefore, the objective of this narrative literature review was to evaluate the existing scientific evidence on the possible beneficial effects of kefir in the prevention or treatment of cancer. To this end, a bibliographic search of the existing scientific literature was conducted using keywords from January 2014 to the present using the PubMed, Cochrane, Science Direct, and Scopus databases. Other sources of information, including archives of public institutions, were also consulted. A total of 16 scientific papers were selected, which investigated the possible anticancer effects exerted by kefir or a bacterial strain isolated from its culture. The collected studies obtained their findings through cell lines or animal models and investigated various types of cancer, but especially colorectal cancer. The results of this review suggest that kefir, through the action exerted by certain of its bioactive compounds (peptides, polysaccharides, and other lipid-based compounds) or a specific bacterial strain, could be beneficial in the prevention or treatment of cancer. However, to date, there are no published clinical trials confirming this anticancer efficacy in humans. Furthermore, the studies analyzed indicate that more in vitro studies are needed to more accurately elucidate the complex mechanisms involved in its potential anticancer effects, as well as well-designed clinical trials in humans using kefir with a standardized and well-defined composition in order to obtain conclusive and reproducible results.

 Keywords: kefir, cancer, mechanisms, benefits, health, preventio

Cancer is a disease with a multifactorial etiology and is one of the leading causes of morbidity and mortality worldwide. The International Agency for Research on Cancer (IARC) estimated that approximately 18.1 million new cancer cases were diagnosed globally in 2020, and that this figure could reach 28 million in the next two decades.¹

The World Health Organization (WHO) estimates that one-third of cancer deaths are due to five preventable factors: tobacco, alcohol, obesity, infectious agents, and ultraviolet radiation. Therefore, a healthy and balanced diet along with daily physical activity could reduce the risk of developing certain types of cancer.

Consequently, there is growing public concern about prevention, leading to an increased demand for functional foods or nutritional supplements that may provide benefits in relation to cancer development.

Among these functional foods is kefir, a fermented dairy product originating from the Caucasus, the Balkans, and Eastern Europe. The WHO and the Food and Agriculture Organization of the United Nations (FAO) describe kefir in the Codex Standard for Fermented Milks as a “starter culture prepared from kefir grains, Lactobacillus kefiri, and species of the genera Leuconostoc, Lactococcus, and Acetobacter growing in a strong symbiotic relationship.” Kefir grains contain both lactose-fermenting yeasts (Kluyveromyces marxianus) and non-lactose-fermenting yeasts (Saccharomyces unisporus, Saccharomyces cerevisiae, and Saccharomyces exiguus).²

This probiotic can be obtained from different types of milk, such as goat, buffalo, sheep, camel, or cow's milk, through microbial fermentation. Kefir grains are composed of a mixture of yeasts and bacteria that live in symbiosis.³ The range of metabolites resulting from the interaction of lactic acid bacteria (LAB), filamentous fungi, and yeasts may be responsible for the beneficial properties derived from kefir consumption.² The popularity of this food means that it is widely available in supermarkets, health food stores, and online, and its grains can even be purchased for home preparation.⁴

The nutritional value of kefir is due to its rich and varied chemical composition, which includes minerals, sugars, proteins, peptides, vitamins, and fats. In addition, the fermentation process significantly enhances the nutritional value of this food due to secondary bioactive compounds such as catechins, vanillin, ferulic acid, and salicylic acid.³

Kefir is known to offer health benefits due to its two main components: a bacterial fraction with probiotic properties and a non-bacterial (soluble) fraction that exhibits antimicrobial activity.² Furthermore, consumption of this probiotic has been shown to exert cardioprotective, immunomodulatory, hypoglycemic, anti-inflammatory, and hepatoprotective effects, among others (Vieira et al., 2021).² Certain bioactive components of kefir, such as polysaccharides and peptides, have also been studied and show great potential for inhibiting proliferation and inducing apoptosis in tumor cells.⁵

Anticancer activity of kefir

The existing scientific literature suggests that kefir is a food with potential beneficial properties against cancer. The antitumor effects of kefir have been attributed to certain bioactive compounds produced during the fermentation process,⁶ including certain organic acids, carbon dioxide, and ethanol, which act as substrates for compounds that play a key role in signaling pathways and cellular biological processes such as apoptosis and proliferation.² Other studies also indicate that the positive effects are due to the immunomodulatory activity of some strains of probiotic bacteria.⁵

Table 1 summarizes the possible mechanisms by which some of the bioactive compounds in kefir could play a protective role in cancer:

Despite the promising nature of this food, the potential beneficial effects have been studied primarily in biochemical or laboratory trials, so more studies in animals and humans are needed to obtain more conclusive results.³

In recent years, several studies have shown that dietary probiotics such as kefir have great potential for the prevention and treatment of cancer. Therefore, the aim of this work is to compile the existing scientific evidence on the potential benefits of kefir consumption in the prevention and treatment of cancer.

For this study, a narrative review of the existing scientific literature was conducted, from which various works were selected, including scientific articles and documents issued by scientific societies.

For the location and selection of the bibliography included, and in order to cover the maximum available and up-to-date information on the chosen topic, specific documentary sources in health sciences were used:

Databases: the PubMed, Cochrane, Scopus, and ScienceDirect databases were consulted. The objective was to identify scientific papers published in the last ten years (2014-2024) that were freely accessible, complete, written in English or Spanish, and that investigated the potential beneficial effects of kefir on cancer. In addition, two articles outside the selected date range were included because they were considered relevant to this work. For the search, the keywords "kefir," "colorectal cancer," "benefits," "prevention," and "mechanisms" were used. A separate search was performed in each database using the aforementioned keywords and the Boolean operators "AND" and "OR," resulting in a number of articles that needed to be screened. A targeted search was also conducted by reviewing the references cited in the most relevant articles. To determine whether an article was useful or not in relation to the study topic, reviewing the abstracts was sufficient in most cases, except for some studies where it was necessary to review the full text.

Additionally, for a better understanding of the pathology and its epidemiology, information was sought from the archives of public institutions such as the World Health Organization and the Spanish Society of Medical Oncology.

A total of 16 scientific studies investigating the potential anticancer effects of kefir over the past 10 years (January 2014 to January 2024) were selected. All articles were experimental in design, with 8 using cell lines, 7 using animal models, and two involving human subjects. Most of the studies aimed to elucidate the effects of kefir on colorectal cancer, although studies investigating its potential benefits in erythroleukemia, breast cancer, gastric cancer, and myeloid leukemia were also reviewed.

Studies in animal models

The high incidence of colon cancer and its possible relationship with the gut microbiota has generated considerable interest in the scientific community. Kefir is an easily accessible food and potentially useful for preventing this type of cancer. Promising results have been obtained in a study that showed that regular consumption of kefir reduced the development of aberrant crypt foci (ACF) by 36% in Wistar rats with colonic lesions compared to the groups that were given milk or water. In addition, consumption of this probiotic food increased the production of short-chain fatty acids, such as propionic acid, and improved the antioxidant response and immunomodulation.⁴

Another study that showed promising results was published by Guiomar and colleagues in 2022. This study used Wistar rats in which colorectal cancer was induced. The animals came from litters with different neonatal diets, which influenced their future inflammatory risk. After weaning, rats that received kefir daily were compared to a control group without supplementation. It was observed that the litters that received kefir daily showed a 100% reduction in the number of tumors in the case of the small litter and a 71.43% reduction in the normal-sized litter (which received greater intake during lactation and, therefore, had unfavorable metabolic programming associated with a higher inflammatory risk). In addition, the gut microbiota profile improved, the production of short-chain fatty acids such as butyrate increased, and the levels of pro-inflammatory cytokines such as IL-6, TNF-alpha, IL-1β, and NO decreased.⁷ (Table 2)

Studies in cell lines

Results in more types of cancer have been found in studies conducted on cell lines.

In a study using a human acute erythroleukemia cell line (KG-1), it was observed that the best results regarding necrosis and apoptosis were obtained after 72 hours using 300 µl of kefir compared to milk and lower doses of kefir (100 and 200 µl). Therefore, the beneficial effect was not only inherent to kefir but also dose-dependent.⁵

The dose-dependent effects of kefir have also been observed in other studies reviewed. One study revealed that the cytotoxic effects on the U87 cell line (glioblastoma) were significantly greater after 48 hours compared to 24 hours and were also dose-dependent (Fatahi et al., 2021). Similar results were observed in a study that investigated a new kefir product, PFT, on human gastric cancer cells. In this case, the authors elucidated the mechanism responsible for this cytotoxicity, which involves a decrease in mitochondrial membrane potential and a reduction in Bcl2 expression.⁸

Another study investigated the effects of kefir on a drug-resistant human colorectal cancer cell line (HT-29), exposing these cells to a dose of doxorubicin for 12 weeks. It was observed that kefir improved this drug resistance through the downregulation of certain proteins involved in drug transport and by increasing the intracellular accumulation of the drug and reactive oxygen species (ROS). This suggests that kefir could be useful as an adjuvant therapy in patients experiencing chemotherapy resistance (Kim et al., 2021).

The anti-apoptotic and antiproliferative properties of kefir were observed in a study where this food was able to reduce the proliferation of colorectal cancer cell lines Caco-2 and HT-29 due to a cell cycle arrest in the G1 phase. An increase in apoptosis was also observed, mediated by a decrease in the expression of TGF-α and TGF-β1 in the HT-29 cell line.⁹ (Table 3)

Recent research has indicated that certain bioactive compounds in kefir may exert preventive and therapeutic effects. Some of the bioactive compounds produced by the microorganisms contained in kefir, including organic acids, bacteriocins, and peptides, can interfere with metabolic pathways involved in regulating cell proliferation, differentiation, apoptosis, metastasis, and angiogenesis. Kefir is also a food that contains a number of probiotic microorganisms, most of which are lactic acid bacteria (LAB).⁵

In a study conducted by Zamberi et al.,¹⁰ in 2016 it was observed that mice infected with the 4TI breast cancer cell line and given a kefir beverage diet for 28 days showed a significant decrease in tumor weight and size, and an increase in the production of helper and cytotoxic T cells, along with an anti-metastatic effect of kefir on the tumors.¹⁰

Furthermore, the extraction of microorganisms from homogenized kefir and the sedimentation of their cell lysate were examined, and the findings demonstrated that the resulting cell lysate, which had significant viscosity and a gelatinous appearance at the concentrations used, showed low toxicity. Findings from another study conducted on a gastric cancer cell line showed that kefir treatment led to a dose-dependent decrease in cell proliferation.⁹

Furthermore, in another study, treatment of the KG-1 blood cancer cell line (acute erythroleukemia) with cell-free kefir extract resulted in a decrease in the proliferation of the erythroleukemia cancer cell line.⁵

The benefits of kefir have not only been studied at the laboratory level, but there are also studies that reflect the possible effects of this food on humans, although to a lesser extent, with mixed results. A study conducted on 40 cancer patients showed that after chemotherapy, the experimental group (kefir) experienced more gastrointestinal discomfort related to the treatment, but a decrease in sleep disturbances compared to the control group (no kefir), with no differences observed between the two groups in terms of quality of life (Can et al., 2009). Another study that evaluated the influence of kefir consumption in cancer patients treated with 5-fluorouracil (5FU) concluded that, at the doses studied, this food had no statistically significant effect on serum levels of pro-inflammatory cytokines or on the incidence of mucositis development (Topuz et al., 2008). However, another study evaluated the benefits of kefir consumption in combination with physical exercise in cancer survivors undergoing chemotherapy and/or radiotherapy for 12 weeks. It was shown that daily intake of this food improved lean body mass, fatigue, gastric discomfort, and biochemical markers such as circulating lipopolysaccharide (LPS).¹¹

Some bioactive compounds in kefir have been shown to exert anticancer effects in in vitro human models. The lack of in vivo studies limits our understanding of the extent of the potential anticancer effects they may have in humans (Vieira et al., 2021).

Based on all the information presented in this work, kefir holds great promise for the food industry due to its safety, affordability, and ease of production. One of the limitations in conducting studies with this food product lies in the differences in microbial composition between industrially produced and traditionally made kefir. Furthermore, this composition also varies depending on geographical, climatic, and cultural factors (Vieira et al., 2021). This heterogeneity in composition presents a significant challenge, as more studies are needed to determine the microbial composition of kefir as rigorously as possible, while simultaneously developing a kefir produced under standardized manufacturing conditions (agitation, inoculum concentration, fermentation time, and temperature) in order to obtain a product with a well-defined composition and thus maximize the potential physiological benefits derived from its consumption.^12-14

Kefir is a fermented product of growing popularity among the population, characterized by containing a wide range of bioactive compounds derived from the symbiotic activity between several of the microbial strains it may contain.

According to the available scientific evidence, it can be considered a promising food, but not a proven anticancer agent. Further laboratory studies and clinical trials in humans are needed, using kefir with a known and standardized bacterial composition, as the heterogeneity of its composition limits the extrapolation of the results.

Furthermore, future studies need to define the mechanisms of action, bioactive compounds with therapeutic utility, possible routes of administration, and appropriate dosage, as these are not currently clearly defined.

None.

The author declares that they have no conflicts of interest.

None.

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