Shorts

briefed by Jule Klotter

A1 Beta-Casein, Inflammation, and Type 1 Diabetes

A1 beta-casein, a protein found in milk from European cows, produces inflammation and symptoms of milk intolerance. Unlike A2 beta-casein found in the milk of genetically pure Asian and African cattle, A1 beta-casein releases the bioactive opioid peptide BCM-7 during digestion. BCM-7 activates µ-opioid receptors in the digestive tract, slowing GI transit time, stimulating inflammatory responses, and increasing mucin production, according to a 2015 review by Sebely Pal and colleagues. Excessive mucus can disrupt GI function and hamper the activities of commensal gut bacteria. Because BCM-7 has several documented negative GI effects, Pal et al. and other research teams hypothesize that A1 beta-casein, not lactose, is the primary cause of milk intolerance.

A1 beta-casein’s effect on people with self-reported lactose intolerance was tested in a 2016 double-blind, placebo-controlled, randomized crossover study led by Sun Jianqin. The researchers enrolled 45 Han Chinese subjects, a population with a high incidence of self-reported lactose intolerance. About half of the volunteers tested positive for lactose intolerance with urinary galactose testing. After a 14-day dairy-free washout period (baseline), each subject drank 250 ml (8 oz.) of milk after two meals per day of A2 beta-casein or normal commercial milk (a mix ofA1 and A2 beta-casein) for 14 days. After a second 14-day washout period, the subject drank the opposite milk for 14 days. The researchers assessed gastrointestinal function using serum and fecal tests, patient symptom reports, and a smart pill (OMOM Capsule, Chongqing, China) to measure GI transit time and inflammation. They also assessed patients’ cognitive processing with the Subtle Cognitive Impairment Test (SCIT).

Reports of delayed GI transit time and milk intolerance symptoms (bloating, abdominal pain, flatulence, heavy stomach, stomach rumbling) were significantly higher when participants consumed the A1 milk compared with baseline. The changes were more pronounced in those who tested lactose intolerant even though both types of milk contained the same percentage of lactose. Drinking A2 milk did not worsen symptoms in either the lactose tolerant or intolerant participants compared to baseline measures. In addition to GI symptoms, cognitive processing speed and accuracy were slower when subjects consumed A1-containing milk. µ-Opioid receptors are also present in the neurological system.

The researchers observed increased small bowel inflammation using the smart pill as well as corresponding changes in inflammation-related biomarkers when some participants drank A1-containing milk (p = 0.042). “It is possible that the intervention period was too short to elicit inflammation in many subjects. Therefore, these findings warrant further examination in a larger cohort or with a longer intervention time,” the authors state.

This study focused on GI effects, but it important to remember that the opioid peptide BCM-7 activates receptors in other systems and tissues as well. Although A2 cow’s milk is sold in New Zealand, the most available A2 source in the US is milk from goats.

Jianqin S, Leiming X, Lu X, Yelland GW, Ni J, Clarke AJ. Effects of milk containing only A2 beta casein versus milk containing both A1 and A2 beta casein proteins on gastrointestinal physiology, symptoms of discomfort, and cognitive behavior of people with self-reported intolerance to traditional cows’ milk. Nutr J. 2 April 2016; 15:35.

Pal S, Woodford K, Kukuljan S, Ho S. Milk Intolerance, Beta-casein and lactose. Nutrients. 2015;7(9):7285–7297.

Berberine

and Diabetes

Over the past decade, berberine has emerged as an effective, plant-based treatment for controlling blood sugar and lipids. The compound is found in the roots and stem of Coptis chinensis (coptis or goldthread), Hydrastis canadensis (goldenseal), Berberis aquifolium (Oregon grape), and Berberis vulgaris (barberry). Plants containing berberine have been used in Ayurvedic and Chinese medicine to treat bacterial, viral, and protozoal infections for over 3000 years. Pharmacological research shows that berberine also has antioxidant, immunomodulation, neurotransmitter, and enzyme modulation effects, according to a 2015 review by Anil Kumar and colleagues.

Bing Pang and Chinese colleagues performed a 2015 literature review of English and Chinese studies on the use of berberine in the treatment of type 2 diabetes. Most of the research consists of laboratory studies that identifies berberine’s positive effects on insulin resistance, insulin secretion, lipid metabolism regulation, and the gut microbiota. Animal research has shown that berberine significantly reduced the number of Firmicutes, which is associated with low-grade inflammation and obesity, and increased the number of Bacteroidetes and other bacteria that produce short-chain fatty acids (SCFAs). SCFAs improve gut barrier function and reduce inflammation, “which may also help to improve obesity and insulin resistance-related metabolic abnormalities,” write Pang et al.

The Chinese reviewers also found a number of small, placebo-controlled studies that lasted between 2 and 6 months. These studies indicate that berberine is as effective as conventional hypoglycemic drugs such as metformin. Unlike metformin, berberine has the additional benefit of reducing triglycerides and cholesterol. Berberine has also been safely used in combination with metformin and/or glipizide. The combination was more effective in controlling blood glucose than the drugs alone in these studies. In addition to its positive effect on glucose metabolism, berberine’s antioxidant and anti-inflammatory properties have made it useful in the treatment of diabetic nephropathy, diabetic neuropathy, and diabetic cardiomyopathy. Pang et al. say that larger, multicenter, long-term, controlled studies are needed to confirm berberine’s therapeutic use in treating diabetes.

In addition to clinical studies, empirical evidence from a respected source is also available. In February 2013, Jonathan V. Wright, MD, reported that berberine “has lived up to its research reputation in clinical observations at Tahoma Clinic, In fact, it turns out that in most of the cases where type-2 diabetes didn’t respond to berberine the patients were misdiagnosed before they came to us….they were actually type-1 diabetics.”

Berberine is nontoxic; it does not produce death when given orally (no LD50). Mild gastrointestinal effects are the primary adverse response. Kumar and colleagues caution against its use in pregnant women because berberine has uterine-stimulatory effects. In addition, two berberine-containing herbs have been withdrawn in Singapore because of the possibility that berberine might worsen jaundice and kernicterus in newborns with glucose-6-phosphate dehydrogenase deficiency.

Practitioners and patients also need to be aware that berberine interacts with several pharmaceuticals, including L-DOPA, cisplatin, fluconazole, warfarin, and cyclosporin A – a list that will probably continue to grow as more information arises. Kumar et al. state, “More studies with a clinical background need to be initiated to evaluate and detect the rare adverse effects of berberine. This is essential to draw a complete safety profile of berberine and to strengthen its applicability.”

Kumar A, Ekavali, Chopra K, Mukherjee, M, Pattabathini R, Dhull DK. Current knowledge and pharmacological profile of berberine: an update. Eur J Pharmacol. 16 June 2015;761:288–297.

Pang B, Zhao L-H, Zhou Q, et al. Application of berberine on treating type 2 diabetes mellitus. Int J Endocrinol. 2015.

Wright JV. Superstar botanical could be your drug-free solution to tackling health complaints from type-2 diabetes to cancer prevention. Nutr Healing. February 2013:19(11).

Bone Broth and Arthritis

“Conventional medical opinion holds that joint problems are inevitable with aging and that damage is irreparable and irreversible. But it appears the human body can revert to the “young” type of cartilage and regenerate young healthy cartilage if provided with the right tools,” write Sally Fallon Morell and Kaayla T. Daniel, PhD, CCN, in Nourishing Broth (New York: Grand Central Life & Style; 2014). “And it’s undoubtedly even easier to prevent the damage to begin with. That means providing the right constituents of cartilage—glycine, proline, glutamine, proteoglycans, and other nutrients found in cartilage-rich bone broth,” Simmering bone, cartilage, and skin from chicken, beef, fish, and other animals in water breaks down collagenous protein into amino-acid-rich gelatin and provides minerals and other nutrients vital for healthy connective tissue.

Although bone broth’s benefits have not been tested in scientific studies, its use in traditional medicine has a long history. Back in the 12th century, Abbess Hildegard von Bingen recommended frequent consumption of broth made from collagen-rich ox feet to prevent and cure joint pain. When Weston A. Price, DDS, visited isolated villages of people who adhered to their traditional whole-food diets instead of processed Western foods in the 1930s, he was astonished at the lack of dental cavities, osteoarthritis, and other degenerative diseases in people of all ages. These people ate “nose to tail,” finding ways to ingest all parts of the animal, including connective tissue.

While bone broth has not been studied, therapeutic use of cartilage and its components has. Nourishing Broth provides information on the formation of cartilage, collagen, and bone and on the extensive research by John F. Prudden, MD, Dsci, and others who investigated cartilage’s anti-inflammatory, immune-enhancing, and wound-healing effects. Cartilage supplementation activates macrophages, killer T-cells, and other parts of the immune system making it useful for diverse conditions. Researchers have reported that cartilage injections and oral supplements benefit people with osteoarthritis, rheumatoid arthritis, scleroderma, psoriasis, wound healing, infectious disease, digestive disorders, cancer, and mental health issues. Anecdotal reports that Morell and Daniel include throughout the book indicate that bone broth has healing power as well.

Nourishing Broth offers practical tips for making bone broth and recipes for broth-rich soups, stews, aspics, and sauces. Although bone broth is not a complete protein, it is a “protein sparer,” increasing the body’s ability to digest the protein in wheat, oats, and barley. It also improves the digestibility of beans and meat protein, providing a proline- and glycine-rich balance to the methionine in meat. Morell and Daniel recommend a daily cup of bone broth from pastured chickens and/or cows for health maintenance and 3 cups per day when dealing with a health challenge. Their web site www.nourishingbroth.com provides sources for collagen-rich bone broth for those who cannot make their own.

Nourishing Broth attests to the adage “Let food be your medicine.”

The Need for Supplements

Many commonly used prescription and over-the-counter drugs deplete vital nutrients. Tieraona Low Dog, MD, explains how the resulting deficiencies seriously compromise health in her book Fortify Your Life (Washington, DC: National Geographic Society; 2016). Low Dog, fellowship director for the Academy of Integrative Health and Medicine (www.aihm.org), is an internationally recognized expert on dietary supplements, herbal medicine, women’s health, and integrative medicine. She wrote the book after her father, who had taken a proton pump inhibitor (PPI) for several years on his oncologist’s advice, was hospitalized twice with dangerously low magnesium and potassium levels. PPIs are known to produce deficient levels of several nutrients including magnesium, calcium, B12, and vitamin D. Prior to hospitalization, her father’s doctors had not tested his red blood cell magnesium level. Rather, they assured him that all was well as long as he ate a good diet.

PPIs are not the only nutrient robbers. Insulin, for example, increases urinary excretion of magnesium. Magnesium is needed for carbohydrate and fat metabolism, cell signaling, nerve impulses, muscle contractions, normal heart rhythm, cardiovascular health, bone health, and more. Yet, how many people with insulin-dependent diabetes get tested for magnesium deficiency or take magnesium supplements? The diabetes drug metformin depletes thiamine, a vitamin that inhibits the development of diabetes-related cardiovascular, kidney, and eye diseases. Metformin also depletes folate, vitamin B12, and possibly CoQ10. People with arthritis often turn to regular use of nonsteroidal anti-inflammatory drugs (NSAIDs) to relieve pain. NSAIDs deplete vitamins B9 (folate) and C, iron, zinc, and melatonin.

Drugs are not the only threats to nutrient deficiency. Years ago, the US government mandated that bread be fortified with B1, B2, B3, B9, and iron to prevent deficiency illnesses such as beriberi and pellagra. Avoidance of breads and cereals because of gluten or GMO/pesticide concerns puts people at risk for B vitamin deficiency. Consumption of iodized salt, the primary source of iodine to prevent goiter, has also declined. Nowadays, people follow recommendations to reduce their salt intake, eat fast food and processed food that does not contain iodized salt, and use noniodized specialty salts. “It’s almost impossible for you to become depleted in one nutrient,” writes Low Dog, “without that deficiency affecting other nutrients and bodily processes.” Consequently, she urges readers to identify their risks for nutrient deficiency and to supplement a nutritious whole food diet with well-chosen dietary supplements.

Fortify Your Life is a wonderful reference about foundational nutrients (vitamins, minerals, and some important nutraceuticals such as CoQ10, probiotics, and omega-3s), their food sources, and the signs and risk factors of their deficiency. Low Dog also gives readers information about evaluating supplements, the use of lab tests to check for deficiencies, helpful nutrients for common ailments, and information about drug–nutrient interactions and depletions. Fortify Your Life is a practical and very helpful book that explains why supplements are absolutely necessary in Western life.

Electromagnetic Hypersensitivity Metabolic/Genetic Markers

In 2014, an international group of researchers identified metabolic and genetic biomarkers specific to people with electromagnetic hypersensitivity (EHS). Although EHS has received little recognition in the US, an increasing number of people, especially in Europe, report negative – at times disabling – effects due to electromagnetic pollution. Any type of exposure can trigger symptoms in a sensitive person, but video display units, radio, television, and electrical installations are the most commonly blamed sources, according to Chiara De Luca and colleagues. EHS has clinical similarities with other puzzling, multisystem conditions such as multiple chemical sensitivity (MCS), fibromyalgia (FM), chronic fatigue syndrome (CFS), sick building syndrome, and Gulf War veteran syndrome. De Luca et al., like other researchers, have hypothesized that people with these hypersensitive conditions “may share common genetic and/or metabolic molecular determinants connected with an impaired capability to detoxify xenobiotics.”

Their 2014 study involved 153 Italians who self-reported having EHS, 147 Italians diagnosed with MCS using Cullen’s criteria and QEESI (Quick Environmental Exposure and Sensitivity Inventory), and 132 healthy age- and sex-matched volunteers who served as the control. The researchers measured 12 metabolic enzymatic (i.e., CuZn superoxide dismutase, catalase, glutathione S-transferase, and glutathione peroxidase) and nonenzymatic redox (e.g., reduced and oxidized CoQ10, plasmatic total antioxidant capacity, and plasma alpha-tocopherol levels) parameters in blood samples taken from all participants. The researchers found that metabolic profiles in EHS participants were comparable to the MCS group, “though generally less pronounced.”

Three factors, however, differentiated EHS sufferers from those with MCS. The authors found elevated oxidation of plasma CoQ10 in the EHS group; “only in electrosensitive subjects, the oxidized/total CoQ10 ratio reached statistical significance versus normal values.” The authors linked this finding to lipophilic antioxidant depletion, which might account for the higher incidence of acute or chronic inflammatory skin conditions among people with EHS. Secondly, the researchers found a significant difference in the omega-6/omega-3 ratio in erythrocyte membranes of EHS and MCS subjects: “The ratio showed a remarkable elevation versus [control] in favor of the more proinflammatory omega-6 PUFA in the MCS group, while EHS values were instead nearly overlapping [control] values. …” Thirdly, the researchers found a genetic difference between people in the EHS and MCS groups. The EHS group showed a significantly higher frequency of the CYP2C19 homozygous mutated *1 allele. The researchers also found “a mutated (null) allele combination of GSTT1 and SGTM1 variants able to predict risk of developing EHS by a 9.7 fold versus [control].” The authors state that their research is by no means conclusive; it is just a beginning in their search for a way to clinically identify electromagnetic sensitivity.

De Luca C, Thai JCS, Raskovic D, et al. Metabolic and genetic screening of electromagnetic hypersensitive subjects as a feasible tool for diagnostics and intervention. Mediat Inflamm. 9 April 2014.

Undenatured Type II Collagen and Osteoarthritis

An undenatured type II collagen (UC-II) supplement, made from chicken sternum cartilage, reduced pain and stiffness in people with knee osteoarthritis more effectively than placebo or glucosamine hydrochloride-chondroitin sulfate supplementation in a 2016 study. The research, led by James P. Lugo of InterHealth Nutraceuticals (Benicia, CA), took place at 13 clinical centers in southern India. An independent statistician performed the data analyses.

The study involved 191 volunteers, ages 40 to 75 years, with moderate-to-severe osteoarthritis (OA) in one or both knees. The volunteers were randomized into three groups. Group 1 received a daily dose of UC-II (40 mg) for 180 days. Group 2 received glucosamine hydrochloride (1500 mg) and chondroitin sulfate (1200 mg), and the third group received a placebo. Every 30 days, clinic staff assessed the volunteers’ pain, stiffness, and physical function of the more compromised knee using the Western Ontario McMaster University Osteoarthritis Index (WOMAC) as well as the Visual Analog Scale (pain) and Lequesne Functional Index. Participants were also asked to record their use of the study product and other medications. Blood and urine samples were taken at the initial screening and on day 180.

After 6 months of treatment, WOMAC scores showed significant reductions in pain and stiffness and improved physical function in the UC-II group compared with the placebo group: pain (24.0 (UC-II) vs. 17.0 (placebo); 95% CI −11.1 to −2.8; p = 0.0003, stiffness (23.8 vs. 17.8; 95% CI −10.4 to −1.6; p = 0.004), and physical function (22.5 vs. 17.3; 95% CI −9.3 to −1.3; p = 0.007). WOMAC pain and stiffness scores were also significantly improved in the UC-II group compared with the glucosamine-chondroitin group at day 180. Although the glucosamine-chondroitin group showed improved WOMAC scores compared with the placebo group, the improvement was not statistically significant. The researchers found no changes in range-of-motion or distance walked in any group.

“The etiology behind UC-II’s impact on OA symptoms is not known,” the authors write. “However, undenatured type II collagen has been shown to protect animals against the onset of joint damage in both OA and [rheumatoid arthritis] experimentally induced arthritis models.” Denatured (e.g., hydrolyzed) collagen is not protective against arthritis, according to animal studies. Although UC-II supplementation reduced arthritic pain in this 6-month trial, the researchers say that longer studies are needed to see whether UC-II can actually reverse knee damage and improve range of motion.

Lugo JP, Saiyed ZM, Lane NE. Efficacy and tolerability of an undenatured type II collagen supplement in modulating knee osteoarthritis symptoms: a multicenter randomized, double-blind, placebo-controlled study. Nutr J. 2016;15:14.