Soy Kefir Grains From KCLM

[Cort]

I don't think that I've posted this before. It's from KClM - a company that's producing soy kefir products. Two small trials indicated benefits - if you took enough of their grains - in ME/CFS/FM patients.

I must say though that their explanation of the benefits seem kind of strange to me; it focused on the efficacy of soy rather than the effects of the bacteria?

They are available for questions; if anyone has any questions that they would like asked let me know - I'm going to send some in.

Soy Kefir – A Novel Functional Food Product with Implications for Chronic Fatigue Syndrome and Fibromyalgia

Soy Kefir product (SKP) is a dry concentrated form of soy kefir drink produced by a patent-pending fermentation process using kefir grains newly developed by KCLM Innovation which was founded at McGill University. Soy Kefir is made by adding kefir grains to liquid based soy. The kefir grains are soft white gelatinous masses which resemble small cauliflower florets containing clusters of bioactive microorganisms held together by Kefiran, a complex polysaccharide or sugar. The grains when added to soy will ferment and incorporate its bioactive microorganisms to create a cultured beverage with a variety of health benefits. It is therefore likely that a combination of biofactors involving Kefir fermentation by-products are involved in the beneficial health effects.

SKP is formulated to concentrate the bioactive components of kefir into an easily consumable form excluding any live bacteria or yeasts due to a heat-inactivation process used in its manufacturing. SKP has shown remarkable improvements in clinical studies in individuals suffering from both pain and fatigue.

Moreover, a double-blinded randomized controlled clinical trial (Ethica Inc.) performed to assess the safety of SKP in humans showed no adverse reactions as was determined by examination of routine blood serum chemistry. In addition, there were also no notable adverse events in heart rate and body weight. Although, some mild adverse GI events were noted which were nevertheless in a range of incidences commonly noted in such studies which generally show initial higher incidences of mild GI upset that usually dissipate.

Two separate clinical trials have tested the efficacy of SKP in patients with either Chronic Fatigue Syndrome or in patients with either Chronic Fatigue Syndrome or Fibromyalgia evaluated for 30 and 60 days. Reported benefits included amongst others; increased energy and vitality levels, significant pain relief and improved physical and emotional well-being.

Both clinical trials utilized a widely-used and highly validated FDA approved health status survey tool known as the SF-36v2 Health Survey. The survey assesses eight health concepts: physical functioning (PF) which defines limitation in physical activities, limitation in role activities (RP); bodily pain (BP), limitation in social activities (SF), general mental health (MH), limitation in usual role activities due to emotional problems (RE), vitality (energy and fatigue) (VT); and general health perception (GH). Scores for people at the top or bottom of a scale can be interpreted by looking at the items and response choices. For example, a person scoring at the bottom of the PF scale is very limited in all activities including bathing and dressing. The survey primarily measures physical and mental health.

Initially, a study was carried out to test the tolerance and effects of the product on a small group of patients. Eleven patients received 56 pouches of 17.5 grams of product, to be taken as 1 pouch twice a day for 4 weeks. Patients answered the SF-36v2 Health Survey questionnaire before and after the 4-week treatment period. Two patients however had to discontinue the treatment due to minor GI discomfort. However, the first patient said she had never felt so energetic since her ailment began.

Moreover, she suggested that she wanted to continue the product for 1 or 2 days a week, as her improvements were remarkable. Increased satiety effects were also noted after the ingestion of the product. All other patients took the Soy Kefir product for 4 weeks. For the statistical analysis, a two-tailed Wilcoxon test was used. The results of the questionnaire were assembled into 8 scales and the average score for each scale before and after the treatment were compared.

The first clinical trial conducted involving chronic fatigue subjects showed significant improvements (alpha risk < 5%) in a variety of parameters tested following a four-week intervention, including improvement in energy levels (VT), bodily pain (BP), energy and mood. Vitality was particularly improved. Anecdotally, three patients with chronic fatigue syndrome have now been taking SKP for over 3 years and feel that they cannot endure without the product. For two of the patients, the SKP is very important for pain relief whereas for the other single patient, the SKP is essential for vitality.

In the second trial, patients suffering with moderate intensity from chronic fatigue syndrome and fibromyalgia were recruited with symptoms of fatigue and widespread muscle and joint pain. Patients were followed for 60 days and SF-36v2 questionnaires were filled at baseline, after 30 and 60 days of treatment. A total of 27 patients completed the study with patients taking either 20g or 30 g of SKP. Statistical analysis aimed at comparing treatment groups at any time point to their baseline values by use of a two-tailed paired t-test. The study appeared to show a time and dose relationship to the SKP regimen. No statistically significant change occurred at 30 days with the 20 g dose with only scales of bodily pain and physical function showing a tendency to improve. However, with the 30 g dose after a 30-day intake, all scores had improvements greater than baseline. Statistically significant effects were observed for bodily pain, role physical and role emotional, with major improvement in scores.

At 60 days of treatment, the 20 g dose for the first time showed statistical improvements over baseline in physical function, role physical and bodily pain. Vitality showed a non-statistical improvement with the 20 g dose. The 30 g dose at 60 days showed similar findings that were observed at 30 days, with all scores statistically increased over baseline values in role physical, bodily pain, role emotional, and vitality scores. The study thus indicated that greater efficacy was observed with the 30 g vs. 20 g dose although improvements were noted in the 20 g dosage with greater length of treatment. Major clinically relevant increases in scores were nevertheless maintained over a more prolonged 60-day period of intake signifying no major diminution of effect.

The mechanisms of action for both pain and energy improvement with SKP are unclear but are likely multi-factorial. With respect to pain, a variety of studies indicate that a soy diet may reduce neuropathic pain in an animal model of partial nerve injury produced by tightly ligating 1/3–1/2 of the sciatic nerve 57 (PSL model) (Shir et al., 2001). The beneficial effects of soy protein on PSL may be related to the reduction in inflammation. Inflammation may contribute to chronic pain states such as neuropathic pain, as proinflammatory cytokines and oxidants produced at the site of nerve injury may be involved with sensitization of nociceptors and hyperalgesia (Wagner et al., 1998).

Neuropathic pain behaviors are reduced with anti-cytokine treatment (Wagner et al., 1998). Dietary consumption of soy protein isolate significantly reduces the carrageenan-induced production of TNF-alpha in macrophages (Yagasaki et al., 2001) and decreases the degree of edema and thermal hyperalgesia following injection of complete Freund's adjuvant (Tall and Raja, 2002).

Recent rat studies have also shown pain relief from thermal hyperalgesia following consumption a combination of soy lipids that was enhanced by intake of soy protein (Perez et al., 2004). Soy lipids have also been implicated in pain relief as rats fed soybean oil had an elevated pain threshold (Yehuda et al., 1986). Other bioactive components in soy could include isoflavones such as genistein that possess anti-inflammatory properties (Sadowska-Krowicka et al., 1998). Genistein has also been shown to inhibit lipopolysaccharide-induced production of the proinflammatory cytokines TNF-alpha, IL-1 alpha, and IL-6 in mixed glia, microglia- or astrocyte-enriched cultures (Kong et al., 1997). Another potential bioactive component is the soluble unique kefir polysaccharide, kefiran, as a recent study has indicated that oral intake of kefir grains induce anti-inflammatory effects in rats (Diniz et al., 2003).

The mechanisms of action with respect to energy improvement are also unclear but are also believed to be multifactorial. Chronic fatigue syndrome has been associated with higher serum angiotensin-converting enzyme (ACE) levels, which has been suggested to reflect damage to the vascular endothelium (Lieberman and Bell, 1993). Hence, a part of the efficacy of SKP in chronic fatigue might be related to its demonstrated ACE inhibitory activity (unpublished data), which has been well demonstrated for other fermented soy products (Kinoshita et al., 1993).

Several supplementation trials have indicated that branched chain amino acids (BCAA) can contribute to combat fatigue and to improve mental and physical performance in athletes (De Lorenzo et al., 2003; Blomstrand et al., 1997). Soy protein is one of the best sources of BCAA and fermentation increases the quantity of soluble proteins. Hence, the digestibility and bioavailability of BCAA from soy kefir would be significantly enhanced to provide a significant enhancement in BCAA uptake.

Amongst the bioactive ingredients in SKP are substantial amounts of isoflavones which have been shown to decrease inflammation, which has been indicated to play an important role for inducing fatigue (Collado-Hidalgo et al., 2006). Maintenance of effective plasma isoflavone concentrations can be achieved with regular daily consumption of SKP. In addition, soy kefir likely contains a host of components that may be involved in the medicinal effects including polyphenolic compounds as well as other bioactive molecules, which might exert cumulative biological effects.

In conclusion, clinically significant improvements in chronic fatigue syndrome patients and fibromyalgia with the soy-derived SKP product is an exciting new approach for treatment of the fatigue associated with this group of patients, particularly since no effective treatment exists by conventional medicine.

 

[Cort]

Soy Kefir Newsletter and SKP

Here's a newsletter produced by KCLM

Soy Kefir A Novel Functional Food Product with Implications for Chronic Fatigue Syndrome and Fibromyalgia

Stan Kubow, Ph.D.1,3 and Dominique Garrel, M.D.2,3

1School of Dietetics and Human Nutrition, McGill University, Montreal; 2Institut de recherches cliniques de Montreal (IRCM), Dpartement de Nutrition, Universit de Montral, Montreal; 3 Scientific Committee, KCLM Research in Nutrition, Inc., Montreal, Canada

Kefir is a probiotic milk drink that originates from the Northern Caucasus Mountains where it has been consumed for centuries and has been valued for numerous health promoting properties (Koroleva, 1988). Indeed, the term kefir derives from the Turkish word, keif, which can be translated as feeling good or good feeling. It is a popular beverage in Eastern Europe, Scandinavia, and numerous countries (Kroger, 1993) and is also sold in Canada and the US.

Kefir has been used traditionally for the treatment of a wide range of metabolic disorders such as atherosclerosis and cancer, gastrointestinal ailments including stomach ulcers and infectious diseases such as pneumonia, bronchitis and tuberculosis, when conventional medical treatment was unavailable (Koroleva, 1988). Controlled clinical trails involving Western science have yet to confirm the utility of most of the above clinical uses although there are Eastern European and Russian publications supportive of these health benefits.

More recently, animal disease model and cell culture studies indicate that kefir and extracts of bioactive components of kefir exert a variety of biological activities that implicate significant health benefits. Studies have generally focused on modulation of the immune system, anti-proliferative and anti-tumorigenic effects against several forms of cancer and anti-microbial effects (Farnworth, 2005). Currently there are no regulations on the sale of kefir or kefir extract as natural health products.

Kefir made by adding kefir grains to various milk products such as cow, soy, goat or other commonly consumed milks. Kefir grains are a soft white gelatinous mass that resembles small cauliflower florets and they contain a wide variety of probiotic bacteria (lactobacilli, leuconostocs, lactococci and acetobacteria) and yeasts. The grains contain clusters of microorganisms held together by kefiran polysaccharides, which are produced by Kefiranofaciens and L. kefir bacteria. Kefir grains are not consumed as part of the final product as they are removed at the end of fermentation. The kefir grains ferment the milk, incorporating their probiotic microorganisms to create the cultured beverage.

The health benefits of kefir are partly dependent on the bioactive components within the food substrate itself that are acted on by the kefir microbes in the fermentative process. Thus, depending on the type of milk used (i.e., bovine, soy, goat, etc.) in the kefir fermentation, the types of bioactive substances such as peptides, polysaccharides, lipids components and other types of biomolecules will differ. The wide variety of bacteria and yeasts present in kefir is unique aspect of this probiotic beverage as normally probiotic foods such as yogurt contain only one or two probiotic bacteria. As each probiotic bacteria are typically demonstrated to produce their own specific bioactive molecules during fermentation, the array of biomolecules generated from the many microbes seen in kefir could produce a more biologically potent probiotic.

Additionally, the microorganisms themselves (either live or dead) and their own metabolites could play a functional role in the proposed health benefits of kefir. It is thus likely that a combination of biofactors involving kefir fermentation by-products are involved in a synergistic manner to exert the systemic health benefits of kefir. It should be noted that recent studies have indicated that viable live bacteria are not necessary to produce a significant biological effects as similar potency can be achieved with dead bacteria, depending on the biological outcome assessed (Mottet et al., 2004).

The kefir beverage made with soy has a tart, refreshing taste that is slightly acidic. Soy kefir product (SKP) is a concentrated dried form of soy kefir drink produced by a patent-pending fermentation process using kefir grains newly developed by KCLM Research in Nutrition, Montreal, Canada, a McGill University start-up company. It is currently being sold under the brand name of Liberation and is available via the websites of www.wykanta.ca and www.wykanta.com. There are many different geographical sources of kefir grain, which vary greatly in their microbial composition, which can lead to differing nutritional outcomes from the kefir-fermented product.

SKP is produced using kefir grains with proven consistency from the All-Union Dairy Institute of Moscow, which has decades of experience in regulating kefir manufacture and development in Russia. SKP is formulated to concentrate the bioactive components of kefir in an easily consumable form but does not contain live bacteria or yeasts due to a heat-inactivation process used, which allows for a more prolonged shelf life. SKP has shown remarkable improvements in clinical studies of individuals suffering from pain and fatigue.

A double-blinded randomized controlled cross-over clinical trial was performed by the clinical research organization, Ethica Inc., that assessed the safety of SKP in human subjects. No adverse reactions as determined by examination of routine serum chemistry were shown, i.e., SMAC-24 - total bilirubin, creatinine, glucose, uric acid, sodium, potassium, BUN, chloride, CO2, calcium, phosphorus, magnesium, total protein, albumin, alkaline phosphatase, AST, ALT, GGT, CK, LDL, cholesterol, HDL, triglycerides, iron. There were also no notable adverse events in heart rate, body weight, and urinalysis. No serious adverse events were observed although some mild adverse events in terms of gastrointestinal events were noted; however, they were in a range of incidences of adverse effects that are very common in such studies. Probiotics such as the soy kefir powder of the present invention commonly show initially higher incidences of mild gastrointestinal upset that usually dissipate with more prolonged intakes.

Two separate open label clinical trials have tested the efficacy of SKP in patients with either the Chronic Fatigue Syndrome or Fibromyalgia (Kubow and Garrel, 2008). Dr. Dominique Garrel at the Institut de recherches cliniques De Montreal (IRCM) carried out clinical research testing the health benefits of SKP for chronic fatigue syndrome subjects for 30 days. A subsequent USA-centered clinical trial involved patients with either chronic fatigue syndrome or fibromyalgia who were evaluated after 30 days and 60 days taking SKP. The latter research study was independently carried out by Oceanova, Quebec City, Canada and Douglas Laboratories, Pittsburgh, PA; a division of Atrium Biotechnologies, Quebec City. From the two above separate clinical trials, reported benefits of SKP included increased energy and vitality levels, significant pain relief and improved physical and emotional well-being.

Research has demonstrated that scales associated with the physical health construct are sensitive to detecting the impact of physical health interventions (Ware and Kosinski, 2001). Similarly, scales that are the strongest measures of mental health are sensitive in detecting the impact of mental health interventions.

REPEATS FINDING FROM LAST PAPER

As case studies consistently showed improvements in several features of the chronic fatigue syndrome, i.e., weakness, lack of energy and strength, pain, and depressed mood, an open label pilot study was carried out by Dr. Garrel (Hotel Dieu Hospital de CHUM) to test the tolerance and effects of the product on a small group of chronic fatigue syndrome patients, most of whom also experienced chronic pain. Eleven patients with chronic fatigue syndrome received 56 pouches of 37.5 grams of product, to be taken as 1 pouch twice a day for 4 weeks.

The clinical trial conducted involving chronic fatigue subjects showed clinically important and statistically significant improvements in a variety of parameters tested by the SF-36v2 Health Survey including improvement in energy levels (VT), bodily pain (BP), energy and mood. Two scales, Bodily Pain and Vitality show differences with an alpha risk < 5% the accepted threshold in sciences and 4 other with an alpha risk ≤ 12% which qualify them for trend because they are compatible with a true effect (and consequently have a good chance to be shown in a larger study).

The clinical trial was extended from a two week to a four-week intervention, as there is evidence that the placebo effects typically fade after a two-week time frame. Hence, the placebo effect was therefore less likely as positive results were seen over the more extended period of four weeks. Vitality was particularly greatly improved, as a significant increase in the sub-scale measure of vitality in the SF-32v2 questionnaire scores was demonstrated with a 12.8-point increase over baseline measures. A 5-point increase is considered to be clinically meaningful (Rowbotham, 2001).

Anecdotally, three of Dr. Garrels patients with chronic fatigue syndrome have now been taking SKP for more than 3 years now and they feel that they cannot endure without the product. For two of the patients, the SKP is very important for their pain relief whereas for the other patient the SKP is essential for vitality.

In the second clinical trial carried on in a US medical clinic, patients suffering with moderate intensity from chronic fatigue syndrome and fibromyalgia were recruited with symptoms of prominent fatigue and widespread muscle and joint pain. Patients were followed for 60 days and SF-36v2 questionnaires were filled at baseline, and after 30 and 60 days of treatment. A total of 18 patients completed the study with 10 patients at 20g and 8 patients at 30 g. Statistical analysis aimed at comparing treatment groups at any time point to their baseline values by use of a two-tailed paired t-test.

The study appeared to show a time and dose relationship to the SKP regimen.
No statistically significant change occurred at 30 days with the 20 g dose with only scales of bodily pain and physical function showing a tendency to improve with scores of 9.1 and 7.0, respectively. On the other hand, with the 30 g dose after the 30-day intake, all scores had improvements greater than 5 points over baseline, ranging from 7.4 for general health to 23.6 for social function and 20.1 for vitality. Statistically significant effects were observed for bodily pain, role physical and role emotional, with major improvement in scores over baseline by 17.2, 22.2 and 23.2, respectively.

At 60 days of treatment, the 20 g dose for the first time showed statistical improvements over baseline in physical function, role physical and bodily pain, which had increases of 7.5, 15.6 and 15.9 over baseline. Vitality showed a non-statistical improvement of 6.9 with the 20 g dose. The 30 g dose at 60 days showed similar findings that were observed at 30 days, with all scores above 5 points and statistically significant increases in role physical, bodily pain and role emotional, and an 18.1 increase in vitality scores over baseline values. The study thus indicated that greater efficacy was observed with the 30 g vs. 20 g dose although improvements were noted in the 20 g dosage with greater length of treatment. Importantly, the major clinically relevant increases in scores over baseline were maintained over a more prolonged 60-day period of intake signifying no major diminution of effect.

For more information on SKP: visit www.wykanta.ca or www.wykanta.com or send your questions to admin@kclmresearch.com or call toll-free 1-800-953-0081