Kefir not just milk

Author: Flavio Tarizzo
Date: 11/03/2013


The word kefir is derived from the Turkish word "keif", which can be trans­lated to good feeling for the sense experienced after drinking it. Kefir is a fermented milk originated in the Cauca­sus with a uniform creamy consistency and a slightly sour taste. Historically, they were considered a gift from Allah among the Muslim peo­ple of the northern Caucasian mountains. Kefir grains were passed from generation to genera­tion among the tribes of Caucasus being considered a source of family wealth.

Kefir: a symbiotic yeasts-bacteria community with alleged healthy capabilities. 2006

Chemical composition
This acidic fermented milk is slightly carbonated and presents small amounts of alcohol . What distinguishes kefir from the traditional fermented milks (yoghourt) is that it is made only from kefir grains, which are composed of yeast and bacteria. The grains are a soft, gelatinous white bio­logical mass, comprised of protein, lipids and a soluble- polysaccharide, the kefiran complex, that surrounds yeast and bacteria in the kefir grains. Kefiran is water-souble glucogalactan produced by Lactobacillus kefiranofaciens(one of the predominant lactobacilli founded).

Kefir: a symbiotic yeasts-bacteria community with alleged healthy capabilities. 2006

Kefir probiotic property
Probiotics are defined as food with viable microorganisms that exhibit a beneficial effect on the host’s health when they are ingested. The most popular probiotic microorganisms are bacteria but yeast have also been studied as probiotics. Kefir is actually considered an example of probiotic mixture of bacteria and yeasts: a complex and tightly packed biofilm can be observed on the exterior of the grains, while the interior mainly comprises unstructu­red material. Microbiota is dominated by lemon-shaped or long filamentous yeast cells growing in close association with bacterial cocci and short or long rod shaped bacteria (lactobacilli). A vast variety of different species of organisms comprising yeast and bacteria have been isolated and iden­tified in kefir grains. Two important criteria for a probiotic are that it must be able to survive in the gastrointestinal environment of the host and that they must present at least one beneficial function (colonization resistance, immunomodulation, or nutritional contribution). The mucosal immune system is one of the first lines of defense in the immune system. It protects an organism’s mucous membranes against infection by preventing the uptake of antigens, microorganisms, and other foreign materials and moderates the organism’s immune response. At birth, a baby’s mucosal immune system is relatively undeveloped, but colonization of the intestinal flora accelerates its development.

Kefir: a symbiotic yeasts-bacteria community with alleged healthy capabilities. 2006

Kefir active ingredient

Kefiran is the main active ingredient of kefir. It is produced by Lactobacillus kefiranofaciens in kefir grains (45 percent of their dry weight). It is an exopolysaccharide having a repeating structure with glucose and galactose residues in the chain sequence and has been suggested to exert many health-promoting effects such as immunomodulatory, hypotensive, hypocholesterolemic activities. It was also tested for antimicrobial and cicatrizing activities against several bacterial species and Candida albicans.

Kefir: a symbiotic yeasts-bacteria community with alleged healthy capabilities. 2006

Kefiran reduces atherosclerosis in rabbits fed a high cholesterol diet 2010

Antimicrobial and healing activity of kefir and kefiran extract. 2005


Kefiran antinflammatory effect
Recent findings indicate that kefiran suppresses mast cell degranulation and cytokine production by inhibiting the Akt and ERKs pathways, suggesting an anti-inflammatory effect for kefiran.
This study investigated the effects of kefiran on mast cell activation induced by antigen. Pretreatment with kefiran significantly inhibited antigen-induced Ca2+ mobilization, the increase in [Ca2+], degranulation, and tumor necrosis factor-α production in bone marrow-derived mast cells (BMMCs) in a dose-dependent manner.

Antigen-mediated crosslinking of FcεRI induces the activation of several protein tyrosine kinases and the phosphorylation of phosphati-dylinositol 3-kinase (PI3K). Phosphorylated PI3K generates phosphatidylinositol3,4,5-triphoshpahte (PIP3), which recruits Akt (protein kinase B) to the plasma membrane where it is activated by 3-phosphoinositide-dependent kinase 1 (PDK1). Additionally, PI3K activates phospholipase Cγ (PLCγ), which leads to the production of inositol 1,4,5-triphosphate and diacylglycerol that elicit increased intracellular Ca2+ concen-trations ([Ca2+]i) and protein kinase C (PKC) activity, respectively. Mitogen-activated protein kinases (MAPKs) and several transcriptional factors are activated.

The PI3K-Akt pathway is known to regulate the downstream pathway of cytokine production by promoting the phosphorylation of GSK3β at Ser9. Pretreatment of BMMCs with kefiran was found to inhibit the phosphorylation of Akt. Similarly, the phosphorylation of GSK3β, a signaling protein downstream of Akt, was promoted upon antigen stimulation and suppressed by pretreatment with kefiran. Therefore, the suppressive effect was also mediated by the inhibition of signaling pathway of ERKs (subfamily member proteins of MAPKs, phosphorylated in mast cells after antigen addition, translocate from the cytoplasm to the nucleus, activate transcription factors, and promote the production of cytokines). Conversely, kefiran did not affect cell viability, degranulation, and cytokine production in the absence of antigen. As described above, kefiran dose-dependently diminished degranulation and cytokine production. The detailed molecular mechanisms by which kefiran diminishes mast cell activation remain unclear, but kefiran probably influences the signaling cascade leading to Akt phosphorylation. Orally administrated kefiran is reported to induce early change in the balance of cell populations in intestine through the interaction of kefiran with intestinal mucosa and to reduce atherosclerosis by oligosaccharides digested from kefiran absorbed in blood. However, the path-way by which kefiran is absorbed and metabolized in the body is not elucidated completely. Kefiran may be effective against allergic and inflammatory disorders if its pharmacodynamic efficacy is improved.

Kefiran suppresses antigen-induced mast cell activation 2012 (detailed biochimical pathway)

This prospective is also designed by another study which used a mouse asthma model, sensitized and challenged to ovalbumin, in which airway inflammation and airway remodeling was produced by ovalbumin.They were treated with kefir (administered by intra-gastric mode) 1 h before the ovalbumin challenge. Kefiran significantly suppressed ovalbumin-induced airway hyper-responsiveness (AHR) to inhaled methacholine. Intra-gastric administration of kefir significantly inhibited the increase in the total inflammatory cell count induced by ovalbumin, and the eosinophil count in bronchoalveolar lavage fluid (BALF). Type 2 helper T cell (Th2) cytokines, such as interleukin-4 and interleukin-13, and total immunoglobulin E (Ig E)levels, were also reduced to normal levels in bronchoalveolar lavage fluid. Histological studies demonstrate that kefir substantially inhibited ovalbumin-induced eosinophilia in lung tissue and mucus hyper-secretion by goblet cells in the airway. Kefir displayed anti-inflammatory and anti-allergic effects in a mouse asthma model and may possess new therapeutic potential for the treatment of allergic bronchial asthma.

Inhibitory effect of kefiran on ovalbumin-induced lung inflammation in a murine model of asthma. 2008

Anti-inflammatory and anti-allergic effects of kefir in a mouse asthma model 2007

Supporting antiinflammatory effects studies:
The early anti-inflammatory effect of Kefir in experimental corrosive esophagitis. 2012

Anticolitis effect of Lactobacillus kefiranofaciens M1 through the production of IL-10
Lactobacillus kefiranofaciens M1 isolated from milk kefir grains ameliorates experimental colitis in vitro and in vivo 2011

Antitumoral effects

Kefir grains also have antitumor qualities, protecting the host against tumor growth. Kefir has been credited with antibacterial and antifungal properties, and has demonstrated higher antimutagenic and antioxidative activity than milk alone. Recently kefir has been reported to have a protective effect on ultraviolet-induced apoptosis in human melanoma cells. Caspase-3 activation has been identified as a key effector of the apoptotic pathway in intestinal cells following irradiation. Caspase-3 is formed by a cleavage of procaspase 3 by caspase-8 or caspase-9. In this active form, caspase-3 plays a role in the proteolytic cleavage of pr oteins, such as the nuclear DNA repair enzyme poly (ADP-ribose) polymerase and inhibitor of caspase-activated DNase that promotes the activation of DNA-cleaving caspase-activated DNase. Results clearly demonstrated that kefir protects the colonic epithelial stem cell region, which is the region most sensitive to DNA damage, and extremely important for regeneration. This antiapoptotic effect of kefir was mediated through the inhibition of caspase-3 activation. Kefir treatment may have possibilities to diminish side effects in the intestinal epithelium of patients undergoing irradiation therapy for malignancy.

The protective effect of fermented milk kefir on radiation-induced apoptosis in colonic crypt cells of rats. 2003

Possible therapy for patients with adult T-cell leukemia
Kefir induces cell-cycle arrest and apoptosis in HTLV-1-negative malignant T-lymphocytes 2011

Although a great number of studies have shown its benefits, the lack of standardized protocols for clinical trials makes the interpretation of results difficult. In addition, the production of kefir in great amounts in industry using kefir grains is not standardized, making big batches with the same characteristics problematic.
Although the evidence might not result conclusive and much further research is required, the data reviewed constitute a promising evidence of the protective roles that kefir shows on health.

Kefir: a symbiotic yeasts-bacteria community with alleged healthy capabilities. 2006

Dario Martinasso
Flavio Tarizzo

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