Kefir

Traditionally, kefir is made by fermenting mammalian milk (usually cow, sheep, goat, or camel^[2]) at room temperature with a symbiotic culture of bacteria and yeast (SCOBY). The kefir SCOBY forms “kefir grains,” which are small yellow- to white-colored clumps that look a bit like cauliflower florets. These grains are made of bacteria and yeast in a matrix of proteins and polysaccharides. During fermentation, the bacteria break much of the lactose down into lactic acid, giving kefir its sour taste; later in the fermentation, the slow-acting yeasts ferment some of the remaining lactose into ethanol and carbon dioxide, resulting in a carbonated, slightly-alcoholic beverage.

Commercial kefir is often prepared not from kefir grains, but from purified cultures of bacteria and yeasts derived from those grains; this is sometimes referred to as "Russian kefir".^[7] Some commercial kefirs are fermented only with a handful of bacterial cultures, omitting the yeasts, and aren’t carbonated.^[8]

There is no generally accepted standard culture for kefir; the term refers to a wide range of active-culture lactic-acid-bacteria fermented milks.

Kefir’s amino acid and mineral profiles are similar to the milk it was fermented from (the fermentation substrate). The finished kefir is 30% lower in lactose than the substrate, and higher in ammonia, serine, lysine, alanine, threonine, tryptophan, valine, lysine, methionine, phenylalanine and isoleucine, than the substrate. Its vitamin profile depends both on the fermentation substrate and on the specific cultures used; one study found that kefir fermentation increased the levels of pyridoxine, vitamin B12, folic acid, biotin, thiamin and riboflavin relative to the substrate. Kefir’s lipid profile also depends on the fermentation substrate.^[1] Finally, the finished kefir contains complex polysaccharides, notably kefiran, which give kefir its buttermilk-like consistency.

Kefir has a low alcohol content of 0.08% - 2%.^[2] The exact value depends on the bacteria and yeasts used and the fermentation process. Commercially made kefir, made with modern manufacturing processes, has an extremely low ethanol content of 0.01% - 0.1%.^[9]

Kefir grains are a complex mix of lactic-acid bacteria, acetic-acid-producing bacteria, lactose-fermenting yeasts, and non-lactose-fermenting yeasts.^[1] Kefir can also be prepared with a starter culture of bacteria and yeasts isolated from previous batches of kefir; this method is used for most commercially prepared kefir. Kefir fermented with such a starter culture contains a lower number and variety of bacteria and yeasts than kefir fermented by kefir grains.^[1]

There are estimated to be more than 300 different microbial species that may be present in any given kefir culture.^[1] That said, the most commonly found bacteria are Lactobacillus kefiranofaciens, Lacticaseibacillus paracasei, Lactiplantibacillus plantarum, Lactobacillus acidophilus, and Lactobacillus delbrueckii subsp. bulgaricus.^[2] Lactococcus and acetic acid bacteria are also present in smaller numbers.^[1] The most commonly found yeasts are Saccharomyces cerevisiae, Saccharomyces unisporus, and the lactose-fermenting yeast Candida kefyr/Kluyveromyces marxianus.^[2]

Kefiran is the bacterially produced polysaccharide that coats the outside of kefir granules and gives kefir its creamy mouthfeel. It’s produced by the bacterium L. kefiranofaciens.^[10] Kefiran is available as a standalone product (not to be confused with KEFIRAN^™, a commercial probiotic encapsulated along with 20mg of kefiran).

In animal and in vitro studies, kefiran has been found to have antitumor, antimicrobial, immunomodulatory, healing, anti-inflammatory, and antioxidant properties.^[6] However, clinical trials are needed to confirm any benefits in humans.

Finished kefir contains many fermentation metabolites in addition to kefiran, including amino acids, fatty acids (CLA), bacteriocins, organic acids, other polysaccharides, and bioactive peptides.^[11]

Kefir has been made from many mammal milks (cow, goat, sheep, yak, bison, camel…), and several milk substitutes including soy milk. The studies referenced in this article all studied kefir made with mammalian milk.

Milk kefir grains will ferment other sugary liquids, such as milk substitutes, fruit juice, or even sugared water^[2]. A kefir-like drink, called “water kefir” or tibicos, can also be made using sugared water and transparent “water kefir grains,” which are a SCOBY related to the kefir SCOBY^[12]. However, this article is focused on milk kefir, made with mammalian milk. For a narrative review of nondairy kefir products, see this paper.

To date, there haven’t been any human clinical trials of kefir as a cancer treatment. A 2015 review of the literature found 7 in vitro studies of the effects of finished kefir on various human cancer cell lines. These consistently showed positive effects (antiproliferative, cancer-cell-killing, or reduction of DNA damage). The review found only 4 relevant in vivo studies, none of them recent, all conducted in mice. These four studies found reduced tumor growth or decrease in tumor size.^[13] These results are promising, but keep in mind that none of these studies are human clinical trials.

There have been two small human trials of kefir during 5-FU chemotherapy for colorectal cancer. One study found that kefir made almost all of the chemo’s side effects notably worse, with more of the kefir group experiencing headache, nausea, vomiting, bloating, constipation, dry mouth, drowsiness, hair loss, weight loss, sweating, poor appetite, and oral mucositis. The exception was difficulty sleeping, which was less common among those taking kefir. The other study, which focused specifically on the side effect of oral mucositis, found that kefir didn't make a significant difference in the incidence of oral mucositis.^[14][15]

One small study looked at kefir as a post-exercise beverage for cancer survivors who had undergone chemotherapy and/or radiation at most 2 years previously. The study put 24 cancer survivors through a 12-week exercise regimen of thrice-weekly hour-long sessions; 12 participants got kefir after each session, and 12 got nothing. Both groups benefited from the exercise, but the kefir group appeared to get more benefit, with greater improvements in lean body mass, depression, fatigue, and gastric distress. The study also saw a decrease in the kefir group's serum lipopolysaccharides (an endotoxin) and different changes in the white blood cell population from the control group. However, there was no milk control in this study, so we don't know whether these effects could have been seen with plain low-fat milk. This study didn't report on adverse effects, other than to note that "most" participants didn't report any.^[16]

Kefir increases fecal microbial load^[17][18], but the evidence is mixed on whether drinking kefir increases the proportion of probiotic bacteria in the stool; it may not have a greater effect on the proportion of probiotic bacteria than drinking unfermented milk.^[19][18] One small study found a significant difference between two different kefirs.^[7]

Three small trials have examined the effects of drinking kefir on constipation. Colorectal cancer patients saw an increase in the chemotherapy side effect of constipation^[14], and children taking antibiotics saw no change^[20]; but a small, uncontrolled study of constipated patients saw a decrease in many of the symptoms of constipation (stool frequency, "bowel satisfaction", improved stool consistency) but not in self-reported scores of straining^[21].

Kefir didn't reduce the incidence of diarrhea or loose stools in children taking antibiotics for uper respiratory infections,^[20] and didn't change stool consistency or frequency in a small study of people with inflammatory bowel disease (IBD),^[18] but it did decrease the incidence of diarrhea in people taking medicine for stomach ulcers (a proton pump inhibitor (PPI) and two antibiotics).^[22]

One small study evaluated kefir in patients with inflammatory bowel disease (IBD). The Crohn's disease patients who took kefir (just 10 participants) self-reported an improvement in abdominal pain, bloating and feeling good after two weeks of kefir, but the study didn't report values and it's not clear whether these improvements were greater than control. Ulcerative colitis (UC) patients who took kefir didn't self-report any improvement. Neither Crohn's nor UC patients reported any change in stool frequency or stool consistency, nor any side effects.^[18]

In patients receiving chemotherapy for colorectal cancer, kefir increased the incidence of bloating. A small study of patients with IBS saw less self-reported bloating in the Crohn's subgroup after two weeks of kefir, but that study didn't report the values, and it's not clear whether it was greater than control.^[14][18]

One small, non-randomised trial of kefir in cancer survivors in an exercise program recorded a pooled "gastric distress" score which incorporated urge to defecate, nausea, gastric reflux, stomach fullness, cramps, and flatulence. The study didn't report on individual symptoms, but did note a 64.7% reduction in this pooled GI distress score in the kefir group after 12 weeks of exercise, compared to a 23.6% reduction for the control group.^[16]

There's limited evidence that kefir may help decrease blood pressure. Two small studies of people with metabolic syndrome noted a modest decrease in systolic and diastolic blood pressure, although it wasn't significantly different than milk control in one trial.^[19][26]

One study of 48 people with metabolic syndrome measured the Framingham Score, which is an estimate of an individual's 10-year cardiovascular risk. The Framingham Risk Score was lowered in the kefir group, compared to yogurt control, but the level of high-sensitivity C-reactive protein (hs-CRP, a measure of inflammation that may indicate increased risk of cardiovascular disease) was unchanged.^[26]

C-reactive protein is a measure of inflammation that may indicate increased risk of cardiovascular disease. Six trials measured either high-sensitivity C-reactive protein (hs-CRP) or C-reactive protein. Four trials measured C-reactive protein: one of patients with IBD, one of cancer survivors in an exercise program, one of endurance athletes, and one of healthy overweight subjects. Levels of CRP in the first three would be expected to reflect inflammation from IBD and exercise respectively. The participants' CRP levels in the trial with overweight participants could be relevant to cardiovascular health, but that trial didn't find any effect. The two trials measuring hs-CRP were conducted in patients with metabolic syndrome, so their results could be relevant to cardiovascular health, but neither trial found any effect from kefir consumption.^[19][26] To sum up, there's no evidence that kefir consumption reduces C-reactive protein associated with increased risk of cardiovascular disease.

No clinical trials have studied kefir's effect on atherosclerosis. However, one small clinical trial of kefir in people with metabolic syndrome did measure levels of oxidised LDL, which is associated with atherosclerosis, and found a modest reduction in the kefir group compared to yogurt control.^[26] See the lipid profile section below as well.

Cytokines are small proteins that are involved in intercellular communication and used by the immune system for cell signaling.

One small, non-controlled Turkish study investigated kefir's effect on cytokines specifically. It found a decrease in IL-8 levels and an increase in serum IL-5 levels during kefir consumption. It also found an increase in TNF-alpha levels, but the increase was insignificant in paired comparisons and the level was borderline between 0th and 6th weeks (p= 0.013). The study noted no significant change in hemoglobin, serum creatinine, ALT, interleukin 1 or TGF-β levels during kefir consumption. Note: this study is available in Turkish only, so Examine.com was not able to review the full study; this information is taken from the study's English-language abstract.^[30]

Several other studies measured cytokines as secondary or experimental endpoints. Three of these also measured TNF-α; in contrast to the above study, which saw an increase, one study found a decrease (but no greater than milk control) and the other two found no effect.^[15][19][16]

One study found that interferon gamma was significantly lower after 12 weeks of kefir (p ≤ 0.05). However, there was no significant difference between the kefir and control (unfermented milk) groups (p > 0.05). ^[19]

No effect was found by any study for: IL-1 beta^[15][30], IL-10^[19], IL-6^[19][15][16].

C-reactive protein is a measure of inflammation. There are two tests for C-reactive protein (CRP). They both measure the same protein, but one test is more sensitive and is called high-sensitivity C-reactive protein (hs-CRP). There's little to no evidence that kefir has any effect on C-reactive protein.

Two clinical trials of kefir have measured hs-CRP, and neither found any effect from kefir consumption.^[19][26] Four clinical trials of kefir measured C-reactive protein: one of patients with IBD, one of cancer survivors in an exercise program, one of endurance athletes, and one of healthy overweight subjects. Among the patients with IBD, the subgroup of Crohn's disease patients saw a decrease in CRP, but not significantly more than control. The studies of kefir in cancer survivors and healthy overweight participants didn't find any effect on CRP. The study in endurance athletes found no significant change in CRP in the kefir groups, in contrast to a significant increase in the training+milk control group; the study's authors noted it's possible that kefir mediated an exercise-related spike in CRP, but since the training+milk group started with a lower average CRP than the other groups, this is tentative at best.

There is limited evidence to suggest that kefir consumption may help with a modest reduction in fasting glucose and HbA1c in people with type 2 diabetes.

Two clinical trials have tested kefir in people with type 2 diabetes (excluding one poor-quality paper^[32]); both found reductions in fasting glucose and HbA1c. One trial, a 42-person trial of adult men newly diagnosed with diabetes and treated with metformin, found a significant decrease in glycated hemoglobin (HbA1c) and fasting glucose in the participants who also received kefir.^[33] In another trial, 60 men and women with type 2 diabetes took either kefir or doogh (an Iranian yogurt drink). After eight weeks, the kefir group's fasting blood glucose was significantly lower than the doogh group's. This trial didn't find any change in insulin levels, but did note that one calculated measure of insulin resistance, HOMA-IR, decreased by about 2 points (likely due to the reduction in fasting glucose). Although HbA1C wasn't one of the trial's preregistered endpoints, the researchers did measure it and noted that the kefir group's serum HbA1C reduced during the study.^[34]

It's important to note that the reductions in fasting glucose and HbA1c weren't huge, certainly not enough to move them out of the diabetic range. There's no evidence to suggest that kefir alone could be an adequate treatment for diabetes. At best, regular kefir consumption could provide a slight reduction in blood sugar and HbA1c.

Two clinical trials have tested kefir in people with metabolic syndrome, with mixed results In one study of 48 men and women with metabolic syndrome, kefir did not affect any anthropometric measures, but the kefir group saw reductions in blood pressure, fasting blood glucose levels, LDL-C, non-HDL cholesterol, triglycerides, and oxidized LDL. Women in the kefir group saw an increase in HDL-C levels. The Framingham Score of cardiovascular risk was lowered in the kefir group, but the level of high-sensitivity C-reactive protein (a measure of inflammation) was unchanged.^[33] Another study of 22 people with metabolic syndrome didn't find any significant differences from milk control, but had a 45% dropout rate.^[19]

The evidence is mixed but leans toward no effect. 2 human clinical trials found LDL decreased in kefir group, but the decrease in one of these trials was similar to that seen with milk. ^[27][26] However, 6 studies found no effect.

The evidence is mixed but leans toward no effect. Six studies found no effect on HDL.^{[17][27][19][34][35][33]} One study saw an increase, but only in female particpants.^[36] And one study saw a decrease, but saw the same decrease for the milk group.^[28]

The evidence leans toward no effect. Only one study found a decrease in triglycerides.^[26] Seven other studies found no effect.^{[19][28][34][17][27][35]}

Kefir may have a lowering effect on non-HDL cholesterol, based on two studies that measured non-HDL cholesterol as a secondary/experimental endpoint. Both studies found a decrease in the kefir group, but evidence is mixed on whether the effect is kefir-specific or just due to the dairy content: One study saw the same reduction in non-HDL cholesterol in its milk group as in its kefir group, but the other saw a reduction in the kefir group and not in its yogurt group.^[27][26]

Kefir doesn't appear to have an effect on total cholesterol. No effect was seen in any of the 8 clinical trials of kefir that measured total cholesterol.^{[19][28][34][17][27][35][33][26]}

This review didn't find any clinical trials designed to study kefir's effect on the kidneys. Creatinine, a metabolic byproduct of creatine, is sometimes used as a biomarker for kidney damage. Creatinine levels weren't a primary outcome for any study, but the 4 clinical trials of kefir which measured creatinine found no effect.^{[30][26][35][33]}

This review didn't find any clinical trials designed to study kefir's effect on the liver. However, several clinical trials of kefir measured liver enzymes and found no significant effect, with the exception of a single trial that found that ALT levels decreased by 13 U/L in kefir+exercise group.^{[19][30][35][26]}

One clinical trial examined kefir's effect on bone mineral density. The average bone mineral density increased in both control and kefir groups, but the difference between control and kefir wasn't significant. The study took blood samples before, during and after the intervention, and found weak evidence for some differences between the kefir group and the control group. However, a lot of irregularities in how this study was registered, analyzed, and reported, coupled with a large loss to follow-up, make this study very weak evidence for any beneficial effects of kefir. Future research is needed to explore this issue.^[37]

In a study of 80 patients undergoing "triple therapy" drug treatment for H. pylori infection (i. e. a proton pump inhibitor (PPI) plus two antibiotics), the patients given kefir had a significantly higher H. pylori eradication rate (78% vs 50%) 45 days after starting treatment, and reported significantly less occurrence of the adverse effects diarrhea, headache, nausea, and abdominal pain at follow-up.^[22]

There have been two small human trials of kefir during 5-FU chemotherapy for colorectal cancer. One study found that kefir made the chemo’s side effects notably worse.^[14] The other study, which focused specifically on the side effect of oral mucositis, found that kefir didn't make a significant difference in the incidence of oral mucositis.^[15]