Letter from the Publisher

A Tour of Klaire Laboratories

In the midst of a family vacation in San Diego, I broke away from our toddler granddaughter, Jacqueline, her mother, Affinity, and my wife, Deborah (pictured here) to take a field trip to Klaire Laboratories facilities in Reno, Nevada. Klaire is part of SFI, a company that originated as an herbal apothecary in the early 1800s. It now has production facilities in England, Switzerland, South Africa, South Korea, and is headquartered in Australia. SFI directs its research to develop high-quality natural products promoting health maintenance, avoiding inclusion of pharmaceuticals and chemicals. Its Reno division is focused on the production of innovative probiotics that adhere to structure and function regulations of supplements as imposed by the FDA. Supplement manufacturing previously labelled as ProThera will now carry the Klaire Labs label produced to meet the same quality control required by the FDA for pharmaceutical manufacturers.

Reno calls itself the “Biggest Little City in the World” and is located very close to the wonderful natural attractions of Lake Tahoe and Squaw Valley ski resort. Klaire Labs is very near downtown and its facility, only recently completed, includes all the features necessary to ensure both product composition accuracy and non-adulteration. All workers in the production side are obligated to be gowned up like surgeons and do not have free access to receiving and shipping. All raw materials are quarantined until they undergo quality control testing both within the facility itself and also by independent lab testing. Once a container of raw material is certified, the container is sealed and affixed with labelling that is digitally coded; monitoring devices ensure that the container may not be moved or tampered with until authorized.

When a raw material is ready to use in the production of a product, for example, a probiotic with several different bacterial strains, the first step is precise adherence to the product’s formulation. There should be neither too little nor too much of the bacterial strain in the product. For this work, manufacturing pharmacists carefully examine the raw material, microscopically, and then digitally weigh it, ensuring a very specific amount of it is put in a container with labelling that is digitally monitored. Once the ingredients are all weighed, they are set aside for mixing. In a unit that looks much like a miniature concrete truck mixer, the raw materials are thoroughly blended in preparation for encapsulation. Mixers are thoroughly washed after each run. The weighing and mixing rooms have air flow hooding to ensure dust and other particulates do not contaminate the processing. In addition, air is maintained at higher than 1.0 atmosphere to ensure that ambient air flows out, again ensuring no dust contamination.

After confirming quality mixing of the product, the mix is introduced into an encapsulating device. Capsules are dropped into supplement bottles that are capped and labelled and then prepared for distribution. All products are digitally monitored once they have been labelled and then are prepared for stocking and/or shipment. Needless to say, such intense mechanical operations need regular maintenance and on-site technicians repair equipment as needed. The overall impression is that the manufacturing facility for Klaire Labs not only meets quality control standards but sets the standard that other facilities should meet.

Just because a company’s label states that it is manufactured with highest quality standards, does not mean that this is true. We should be able to ask the supplement manufacturer to provide information about its quality control and manufacturing process. Inexpensive supplements (and some expensive supplements) undoubtedly are not produced with reputable quality control and may be adulterated with heavy metals and chemicals.

Klaire Laboratories will permit interested individuals to take a tour of its facilities if permission is requested in advance. All supplement manufacturers should offer similar tours of their manufacturing sites. Why not request a tour and assess the company’s quality standards?

A Probiotic Support for Depression?

Alcock, Maley and Aktipis review how eating behavior can be manipulated by the gastrointestinal microbiota.¹ They postulate that microorganisms have two potential mechanisms for how microorganisms might alter our eating behavior: (1) the organisms create cravings for eating foods that might suppress survival of competitive microorganisms; (2) the microbiota might elicit “dysphoric” emotions until we eat food that benefits their survival. Alcock et al. point out that a diverse microbiome composed of a large number of differing microorganisms has a greater ability to mutually provide for nutritional needs compared to a microbiome with less diversity. When the microbiome has less diversity, there is greater neurochemical signaling to eat more to provide nutritional needs; obese hosts tend to have limited microbiome populations. Numerous studies are cited of how microorganisms can play an important role in host eating behavior, including how their metabolic activity can modify the host’s mood. Lactobacillus in breast milk is observed to increase tryptophan metabolism and have a respective calming effect on the suckling infant. When microbiota was transferred to “germ-free” mice from anxious mice, the cohorts were notably more agitated than prior to the transplant. On the other hand, stressed mice fed Lactobacillus rhamnosus had observable reduction in cortisone levels accompanied with calming behavior.  Alcock et al. review neural mechanisms, particularly involving the vagal nerve, of how microbiota can alter eating behavior. Organisms of the microbiome have adapted to produce neurochemicals that closely mimic the human neurochemicals directly influencing emotional response. Alcock notes that the microbiome can be modified by the use of prebiotics and probiotics, microbiota transplantation, antibiotics, and other methods. The authors posit that these approaches may be used to modify our psychiatric state as well as cognitive functioning.

Steenbergen, Sellaro, van Hemet, Bosch, and Colzato, researchers in the Netherlands, have demonstrated the efficacy of multispecies probiotics in a randomized control trial on sad mood.² As noted by Alcock, it has been hypothesized that probiotics may have a direct impact on depression. However, human studies of the effectiveness of probiotics on depression have been limited. The Dutch investigators tested a probiotic blend containing Bifidobacterium bifidum W23, Bifidobacterium lactis W52, Lactobacillus acidophilus W37, Lactobacilus brevis W63, Lactobacillus casei W56, Lactobacillus salivarius W24, and Lactococcus lactis (W19 and W58).

40 healthy individuals were studied: 20 received the probiotic mixture for one month, while 20 received a placebo mixture in a triple-blinded, randomized trial. Sad mood was assessed using the Leiden index of depression sensitivity. Compared to control, treated individuals revealed a significant reduction of sad mood thought to be manifested by less violent thoughts and worrying. The authors affirm that this is the first evidence that probiotics have a significant effect on diminishing sad mood and suggest that it may be a helpful adjunct for depression.

Elsbeth Pekelharing on Probiotics Science

At the Reno Klaire Lab tour, Elsbeth Pekelharing, Science Liaison for Winclove Probiotics, presented a primer on probiotics science; her lecture serves as the basis for the following editorial notes. Winclove is a private business-only probiotic manufacturer providing more than 70 probiotic strains to 80+ commercial manufacturers in 35 countries. Strains of microorganisms are specific and represent a subspecies of the designated organism. For example, Lactobacillus acidophilus only names the species, but Lactobacillus acidophilus W37 is the strain. Different strains can have very different properties; it cannot be assumed that a product labelled as Lactobacillus acidophilus either contains Lactobacillus acidophilus 37 or functions in the same manner. As a general rule, formulations with multiple species will function better than ones with fewer probiotics species. It is not clear that having a preparation with very high numbers of multi-species that have not been strain identified will provide ideal clinical applications. Furthermore, there is the significant possibility that poorly manufactured formulations will not survive adequately to interact with the gastrointestinal microbiome.

Probiotic microorganisms have at least three major functions within the GI tract: (1) microbe-microbe interaction, for example, growth inhibition of the microbiome organisms; (2) local barrier effects of the gastrointestinal mucosa by microbe-barrier interaction, for example, mucous production; and (3) systemic internal effects, for example, changes in hormone and cytokine production. These functions establish the two-way communication between the gut and brain (see figure). The question is how effective the probiotic formulation is to optimize the gut-brain communication.

Intestinal permeability, a gastrointestinal dysfunction, is largely dependent on disruption of the intestinal cell barrier. At a cellular level there is an absence of a “thick” mucous layer, “strong” tight cellular junction, and epithelial cells in “good condition.” Ideally the probiotic microorganisms should counter intestinal permeability in three ways: (1) stimulate regulatory response by increasing the production of IL-10; (2) inhibit pro-inflammatory response by decreasing mast cell activation and increasing LPS breakdown; and (3) strengthen intestinal barrier function through increasing trans-epithelial electrical resistance (TEER). These functions can be studied for individual microbial strains; an effective strain will demonstrate improvement of TEER, for example, while an ineffective strain will not. Assessment of barrier function is necessary to understand the effectiveness of a probiotic preparation. For example, clinical testing has demonstrated optimization of TEER with Lactococcus lactis W19 and W58 but no other strains. GI survival of the microorganism is another important criterion in selecting strains.

Our patients inform us that they are using a probiotic. We can no longer just accept the fact that the preparation they are using containing over 100 billion organisms means that an effective probiotic is being used. We will need to understand its quality control, strains delineated, and whether it is addressing the applications required.

Bonnie Nedrow, ND, on Nonalcoholic Fatty Liver Disease

While we associate fatty liver disease with alcoholism, non-alcoholic fatty liver disease has become a highly prevalent problem. Associated with obesity it is estimated that as little as 15% and as much as 52% of the population has NAFLD. As reviewed in this issue by Dr. Bonnie Nedrow, much of the same factors that bring about metabolic syndrome with obesity, dyslipidemia, and hypertension are involved directly in damaging the liver and causing NAFLD. Insulin resistance is associated with diabetes and pre-diabetes, but it is the key mechanism for insulting the liver bringing about fatty deposition in the liver. While we are counseling our pre-diabetic patients about the hazards of inadequate glucose control, we need to bring fatty liver disease into the discussion because this is not a process that will happen in the future—it is currently underway and progressing. While many of the strategies we need to employ for insulin resistance are applicable to managing NAFLD, there are biochemical mechanisms impacting the liver that we don’t associate with diabetes. Nedrow’s review offers some innovative approaches ready to use in the office immediately.

Jenna Henderson, ND, on Myths Related to Treating Kidney Disease (Cover Story)

Patients seeing us for fibromyalgia, cardiovascular disease, autoimmune disease, or cancer are generally treated vigorously, asked to modify their diet, implement an exercise program, and initiate an extended herbal, nutraceutical, and homeopathic supplementation regimen. In many circumstances prescription medications may be added or reduced, and intravenous or parenteral medication or nutraceuticals are frequently implemented. However, all of this regimentation is called into question with patients who have chronic kidney disease (CKD). The one major contraindication for proceeding with intravenous chelation therapy would be a reduced eGFR (estimated glomerular filtration rate) and elevated creatinine. Despite some commentary that chelation improves kidney function, this is rarely the case; patients with CKD will trend to increasing creatinine levels if routine chelation protocol is followed. And, much the same, a robust supplementation regimen, liver cleanses, and detoxification treatment will likely worsen kidney functioning. So, what is the integrative and naturopathic practitioner to do with the CKD patient?

In this issue Dr. Jenna C. Henderson, a CKD patient herself, tackles this question. Henderson wants practitioners to confront the major misconceptions of kidney disease. At the very least, she would like doctors to become knowledgeable about the myths plaguing the internet. Herbal diuretic? Alkalinize the urine? Lower protein in the diet? Fasting? “Yes” and “no.” These strategies cannot be employed “automatically” without evaluating and monitoring the patient. Avoidance of dialysis for severe Stage 5 chronic kidney disease should never be the advice of an integrative practitioner; we should be looking for supportive treatments to complement dialysis.

1. Alcock J, Maley C, Aktipis C. Is eating behavior manipulated by the gastrointestinal microbiota? Evolutional pressures and potential mechanisms. Bioessays. 2014 Oct; 36(10): 940-49.

2. Steenbergen L, Sellaro R, van Hemert S, Bosch J, Colzato L. A randomized controlled trial to test the effect of multispecies probiotics on cognitive reactivity tos ad mood. Brain Behav. Immun. 2015. http://dx.doi.org/10.1016/j.bbi.2015.04.003