Dr. Bray Links

Wednesday, April 27, 2016

Global marine pollutants

Persistent organic pollutants (POPs) are hazardous, man-made chemicals that endure in the environment and bioaccumulate in animals. Their environmental persistence ensues from properties such as halogenation and hydrophobicity that slow degradation and promote partitioning into organisms. At the same time, these properties also favor POP bioaccumulation by slowing their elimination. Indeed, although all animals have numerous metabolic enzymes, conjugation systems, and transporter proteins that normally act to eliminate xenobiotics, these systems appear ineffective at limiting POP bioaccumulation.

A critical step toward understanding the persistence and organismal impacts of POPs is defining their interactions with xenobiotic elimination systems. Drug transporters are plasma membrane proteins that both limit the entry of foreign chemicals into the body and speed their clearance, and are already well studied for their roles in drug disposition (1). Previous studies have suggested that environmental chemicals can also interact with drug transporters, such as P-glycoprotein (P-gp), but that they are poorly transported, and that these interactions ultimately lead to inhibition of transporter function (2–10). Of concern is that this inhibition reduces the efficacy of transport, thereby sensitizing animals to toxic chemicals that would otherwise be effluxed (11, 12).

Here, we took a multilevel approach to examine transporter-pollutant interactions, from levels in the environment down to the cocrystal structure of an environmental chemical bound to the transporter. We focused on P-gp, an adenosine triphosphate (ATP)–binding cassette (ABC) transporter (13–15), which plays a major role in the disposition of xenobiotics (1, 16) and which is one of the best-studied drug transporters to date. P-gp has a large binding pocket that interacts with a wide variety of structurally divergent hydrophobic molecules (16–19), and binding within this large pocket can have different impacts on the transporter, from stimulation to inhibition of function (20, 21). P-gp is conserved and is typically expressed at environmental barrier tissues, such as the small intestine or gills (22–24).

To identify POPs that interact with P-gp, we used robust biochemical and cellular assays of mouse and human P-gp and identified specific congeners that inhibit this transporter. Using x-ray crystallography, we validated the binding of one of these chemicals, polybrominated diphenyl ether (PBDE)–100, deep within the ligand pocket of the transporter, providing the first snapshots of P-gp bound to a pollutant. To gain insight into the environmental relevance of P-gp inhibitors, we measured their levels in yellowfin tuna (Thunnus albacares) from the Gulf of Mexico (GOM) and used these data to examine the effects of a representative POP mixture on the transport function of the human P-gp.


Why Eating Farmed Salmon May Make You Fat

A study provides more evidence that a diet high in farmed salmon contaminated by persistent organic pollutants - POPs - contributes to weight gain and increases the risk of diabetes.

The results are consistent with a growing body of research on people, linking POPs exposure to type 2 diabetes. Mice fed contaminated salmon gained twice as much weight and developed more severe insulin resistance measures than mice that ate no salmon but the same amount of fat.

When the researchers fed the mice salmon whose POPs levels had been reduced by around 50 percent, the health effects were also reduced.

The researchers could not say whether these effects are due entirely to POPs or other factors inherent in the fatty fish diet. Further work should test whether a complete avoidance of POPs further reduces weight gain and insulin resistance.

According to another study funded by the Pew Charitable Trusts and published in the journal Science, eating more than a meal of farm-raised salmon a month, could also increase the risk of getting cancer later in life.

"We are certainly not telling people not to eat fish," said David Carpenter of the University at Albany, N.Y., "...We're telling them to eat less farmed salmon."

The average dioxin level for farm-raised salmon was 11 times higher than in wild salmon - 1.88 parts per billion compared with 0.17 ppb. For PCBs, the average was 36.6 ppb in farm-raised salmon and 4.75 in wild.

Animals absorb those pollutants through the environment, storing them in fat that people then eat. High levels are believed to increase the risk of certain cancers and, in pregnant or breast-feeding women, harm the developing brains of fetuses and infants.

What Did They Do?

In a new experiment using mice, scientists tested the effects of eating farmed salmon on weight gain and metabolism changes including insulin resistance, an indicator of diabetes. The researchers also tested whether POPs played a role in these factors.

The scientists fed groups of 8-week-old male mice different diets for eight weeks. These included a control diet, a very high-fat diet (72 percent fat) without farmed Atlantic salmon, a very high-fat diet with commercially-farmed Atlantic salmon and a lower fat/high carbohydrate Western-style diet (29 percent fat) with or without salmon.

Another group of mice was fed salmon whose POPs levels had been reduced by approximately 50 percent.

The researchers measured weight gain, body fat to track obesity and insulin resistance and glucose tolerance, both of which indicate increased risk of developing diabetes. They also measured levels of POPs in tissues and fat, including organochlorine pesticides, dioxins, furans and different types of polychlorinated biphenyls.

What Did They Find?

They found the mice fed the high-fat diet with farmed salmon gained roughly twice as much weight as mice fed the high-fat salmon-free diet, even though the diets contained the same total amount of fat. A big difference is the type of fat in each diet. The salmon diet had lower omega-6 fatty acids and higher omega-3 fatty acids than the diets without salmon.

The higher weight gain was due to greater absorption of fat into the body.

The high-fat, contaminated-salmon diet also worsened insulin resistance and glucose intolerance, indicating a diabetic state in the mice.

Interestingly, the authors found similar patterns when they tested the effects of salmon in the lower-fat, Western diet. Though the effects were smaller, the mice fed salmon gained more weight and had increased insulin resistance.

Finally, mice fed the salmon diet with reduced POPs had slightly less weight gain, lower body fat and decreased indicators of type 2 diabetes compared to mice fed salmon with higher POPs levels.

What Does it Mean?

The study with mice provides more evidence that eating a prolonged diet with contaminated fatty fish may increase obesity and raise the risk of insulin resistence that may lead to diabetes. While the exact reasons for the changes aren't clear, pollutants in the fish contributed some to the increased risk of metabolic disease seen in the study, the researchers report.

The results show that eating the POPs-contaminated farmed salmon led to greater weight gain and higher predisposition to type 2 diabetes compared to a salmon-free diet with the same amount of total fat.

The findings raise a number of questions, including whether this pattern is true for all fish -- farmed or not -- or seafood in general and if it carries over to other fatty, foods, such as meat and dairy, which may also contain POPs. The researchers could not say whether these effects are due entirely to POPs or other factors inherent in the fish diet. Further research should test whether a complete avoidance of POPs further reduces weight gain and insulin resistance.

Prior research has tried to understand the influence of fish intake on type 2 diabetes and other metabolic diseases. Yet, the interplay between the two remains ambiguous. Overall, recent long-term human studies from the United States and Europe suggest a connection.

This experimental study is one of the first to test the idea in animals. The study supports those past human studies because it finds similar results.

Other lab and animal studies by the same research group have found POPs can interfere with the beneficial effects of salmon oil and impair insulin actions. This study suggests the same but provides a new twist. It is unique because whole fish fillets -- not just fish oil alone -- were used.

POPs levels in the fish's fatty tissues were similar to what has been measured in the people. This agrees with past research showing that environmentally relevant levels of one type of POPs -- polycyclic byphenyls (PCBs) -- can affect insulin resistance.

Since salmon are a complex mix of many different nutrients and contaminants, it will require more intensive study to uncover the mechanism behind these patterns. For right now, the researchers suggest that limiting "daily and long-term exposure to POPs may therefore represent a novel and attractive approach to slow down the uncontrolled rise of metabolic diseases."



Small-Fiber Neuropathy in Prediabetes Less Benign Than Believed

In a new study of patients with small-fiber neuropathy, analyses of the density of nerve fibers in skin biopsies from the leg, taken 3 years apart, revealed that, contrary to what is taught in medical school, the longest nerves did not degrade first.

Instead, the rate of deterioration of small nerve fibers was similar in the ankle, midleg, and upper leg, Mohammad A Khoshnoodi, MD, from Johns Hopkins University, Baltimore, Maryland, and colleagues report, in the study that was published online April 11 in JAMA Neurology.

Moreover, the rate of nerve deterioration was similar whether the small-fiber neuropathy was idiopathic or associated with diabetes or with impaired glucose tolerance (prediabetes) — which suggests that prediabetes may be more damaging to motor nerves than once believed.

"We anticipated that people with diabetes would have greater progression than people with prediabetes, but that was not the case," senior author Michael Polydefkis, MD, also from Johns Hopkins University, told Medscape Medical News.


Sublingual Immunotherapy Improves Dust Mite Allergy

Sublingual immunotherapy lengthened the time to first moderate or severe exacerbation during a period of corticosteroid reduction among patients with house dust mite–related asthma, according to a multicenter randomized study published in the April 26 issue of JAMA.

The study reported an estimated absolute reduction at 6 months of 9 to 10 percentage points, mainly as a result of the mitigation of moderate exacerbations. Sensitization to dust mite allergen is present in as many as 50% of patients with asthma, and exposure to it has been linked to asthma severity.

Researchers led by pneumologist J. Christian Virchow, MD, from the Department of Pulmonology/Intensive Care Medicine at the University of Rostock in Germany, conducted the double-blind, randomized, placebo-controlled trial between August 2011 and April 2013 at 109 European sites. The study population consisted of 834 adults (mean age, 33 years; 48% women; 99% Caucasian) with poorly controlled house dust mite allergy–related asthma and allergic rhinitis. Patients with severe unstable asthma were excluded.

Participants were randomly assigned to one of three groups: placebo (277 patients) and two different doses of sublingual tablet, with biological activity expressed in standardized quality house dust mite units (SQ-HDM): 6 SQ-HDM (275 patients) or 12 SQ-HDM (282 patients). Participants placed one tablet under the tongue daily and received treatment for a maximum of 18 months. In addition, the patients used inhaled corticosteroids and the short-acting β2 agonist salbutamol.

During the final 6 months of the study, corticosteroids were reduced by 50% for 3 months and then withdrawn for 3 months. Patients recorded symptoms, medication use, and lung function twice a day in electronic diaries.

Evaluating efficacy during this period in the 693 patients completing the study, the researchers note that both active doses significantly reduced the odds of moderate or severe asthma exacerbation, which was the primary endpoint, compared with placebo. Specifically, the hazard ratios were 0.72 (95% confidence interval [CI], 0.52 - 0.99) for the 6 SQ-HDM group (P = .045) and 0.69 (95% CI, 0.50 - 0.96) for the 12 SQ-HDM group (P = .03).

The absolute risk differences in the intervention groups vs in the placebo group were 0.09 (95% CI, 0.01 - 0.15) for the 6 SQ-HDM group and 0.10 (95% CI, 0.02 - 0.16) for the 12 SQ-HDM group. No significant difference was observed between the active groups (hazard ratio, 0.96; 95% CI, 0.68 - 1.37; P = .84).

The treatment groups also showed a significant rise in allergen-specific immunoglobulin 4 antibody, a key secondary outcome. However, the authors saw no significant changes in the Asthma Control or Asthma Quality-of-Life questionnaires with either active dose.

"To our knowledge, this is the first controlled trial to show that adult patients with [house dust mite] allergy-related asthma who were not well controlled taking [inhaled corticosteroids] can achieve an improvement in asthma control as measured by time to first asthma exacerbation with a sublingual tablet formulation of [house dust mite] allergen immunotherapy," Dr Virchow and coauthors write.


Obamacare’s Taxpayer-Subsidized Failure

Here’s some bad news for the insurance industry: Unexpectedly generous corporate subsidies didn’t save companies selling Obamacare policies from bleeding red ink.

The worse news: Those subsidies are set to expire in 2017, meaning that insurers will have to make ends meet without billions in handouts.

Those are among the matters discussed in a study, published April 25 by the Mercatus Center, authored by Brian Blase, Edmund Haislmaier, and me. Our study, based on detailed data derived from insurer regulatory filings for the 2014 benefit year, finds that companies that sold Obamacare plans in the individual market lost more than $2.2 billion, despite receiving $6.7 billion (an average of $833 per enrollee) in “reinsurance” subsidies. Those reinsurance payments were 40 percent more generous on a per-enrollee basis than insurers had expected when they set their 2014 premiums.

The reinsurance windfall was not enough to put companies in the black. Our study found that insurers collected an average of $4,433 in premiums per enrollee (much of which came directly from the government in the form of subsidies for low-income individuals), but paid an average of $4,624 per enrollee in medical claims, a prescription for disaster.

The $833 per-enrollee reinsurance subsidy mitigated the disaster but still left many insurers with too little to cover their administrative costs. So they turned for help to another government subsidy known as “risk corridors,” seeking an average of $273 per enrollee to stanch the bleeding. Even if insurers had received all the reinsurance and risk-corridor handouts they sought — an average of $1,106 per enrollee, or nearly 25 percent of premium — they still would have lost money, our study found.

But they didn’t get all they wanted. Congress clamped down on the risk-corridor program, thwarting the administration’s plan to turn it into a corporate entitlement. Instead, Congress stipulated that the program be budget-neutral, authorizing the government to transfer money from insurers that booked “excess” profits to those that suffered “excess” losses, but barring the use of  government payments to insurers through the program. Because excess profits — or any profits at all — were scarce, insurers recovered only a fraction of their risk-corridor claims.

Congress has also begun to question whether companies are entitled to all the reinsurance subsidies they are receiving. The Obamacare statute is clear on this point. Under its terms, the government is authorized to collect billions of dollars, most of it from people enrolled in employer-sponsored coverage to finance the reinsurance program. The Centers for Medicare and Medicaid Services (CMS) collected an assessment of $63 per enrollee ($252 for a family of four) from virtually every private insurer in 2014 and $44 per enrollee in 2015.

The law required CMS to remit $2 billion of these collections to the Treasury for the 2014 and 2015 benefit years (a total of $4 billion), reserving the rest for reinsurance subsidies. The nonpartisan Congressional Research Service concluded that the obligation to transfer these funds to the Treasury — rather than to insurers — is unambiguous and clear.

But when collections came up $3.5 billion short over the first two years, CMS chose to ignore its legal obligation; instead, CMS diverted that sum from the Treasury to insurance companies in the form of reinsurance subsidies.

CMS’s $3.5 billion heist was the product of an abrupt and mysterious shift in position. In a March 2014 rulemaking, CMS declared that the Treasury would get its share of the funds even if collections fell short. But ten days later, CMS did an about-face, announcing it would stiff the Treasury if there was a shortfall.

Appearing before the House Energy and Commerce Subcommittee on Oversight on April 15 this year, CMS administrator Andy Slavitt was at a loss to explain why the agency he now heads changed its rules so swiftly and dramatically. He repeatedly evaded the question, telling the committee he wasn’t at CMS in 2014 when it made the decision to fleece the Treasury. That’s certainly true. Slavitt was an executive with United Healthcare, the nation’s largest health insurer, when the agency he now heads reversed its position.

Congress may reverse it back. If it required the administration to repay the $3.5 billion it pilfered from the Treasury before doling out more reinsurance money, the industry would surely feel the pinch.

It already is an uncomfortable moment for insurers, as they decide whether to continue to sell Obamacare policies in 2017. Under the law, the reinsurance and risk-corridor programs will expire at the end of this year. That means next year’s premiums will have to cover medical claims and administrative costs without the crutch of government subsidies.

Our study shows that some companies may be better positioned than others to absorb the loss of those subsidies. Most companies with restrictive provider networks fared reasonably well in 2014, as did insurers in a handful of states, including California. Others will choose between pulling out of the exchanges and seeking premium increases, a move that requires regulatory approval and risks driving away healthy customers, already in short supply.
None of this is good news for Obamacare, insurers, or consumers, who wonder what’s so affordable about the Affordable Care Act.


Monday, April 25, 2016

Adverse Reactions to Antihistamines More Common Than Thought

Antihistamines are associated with a variety of adverse reactions in children, including headaches, sleepiness, rashes, behavioral changes, and convulsions, new research suggests.

Although prior studies have suggested that newer antihistamines have few adverse reactions in children, there are some reactions worth noting, according to Tjalling W de Vries, MD, from the Department of Pediatrics, Medical Centre Leeuwarden, the Netherlands, and Florence van Hunsel, PharmD, PhD, from the Netherlands Pharmacovigilance Centre Lareb, Den Bosch, the Netherlands. "[T]he [adverse drug reactions (ADRs)] we found were never described in these safety studies, which were all sponsored by the manufacturers."

They continue, "When prescribing antihistamines, clinicians should be aware of ADRs such as somnolence, altered behaviour, skin eruptions and headache. Moreover, there is a possible relation between convulsions and (des)loratadine."

Dr de Vries and colleagues report their findings in an article published online April 18 in the Archives of Disease in Childhood.


Adding Risk Markers Improves Breast Cancer Risk Prediction

Adding a genetic risk score, mammographic density, and hormone levels — all biologic markers of risk — can significantly improve upon the current models for breast cancer risk prediction, according to data presented here at the American Association for Cancer Research (AACR) Annual Meeting 2016.

"Several prior studies have evaluated the added predictive value of a genetic risk score or mammography or both to improve upon the current Gail model, but none has used all three risk markers," presenter Xuehong Zhang, MD, ScD, assistant professor of medicine at Harvard Medical School, Boston, Massachusetts, told Medscape Medical News.

"We have shown that while each of the three biological markers can improve risk prediction, all three together improved the model the most," he added.

Dr Zhang was referring to the Gail and the Rosner- Colditz models, which have been validated and are currently used for predicting risk for breast cancer. They also are useful for making chemoprevention and screening recommendations.

The Gail model takes into account traditional risk factors, such as age, age at first menstrual period, age at first birth, history of breast cancer, and atypical hyperplasia on biopsy. The Rosner-Colditz model includes these factors plus body mass index, alcohol intake, and other well-known reproductive factors.

Dr Zhang and his colleagues conducted a nested case-control study within the Nurses' Health Study (NHS) and NHS II. Collectively, the investigation included 4006 case patients/7874 control patients for the Gail model, and 2665 case patients/5455 controls patients for the Rosner-Colditz model.

The genetic risk score was calculated on the basis of 67 single-nucleotide polymorphisms. Mammographic density was assessed among women who provided blood samples. Estrogen, testosterone, and prolactin levels were measured using prediagnostic plasma samples.


Eat More Dirt

Doctor of Natural Medicine and wellness authority Dr. Josh Axe delivers a groundbreaking, indispensable guide for understanding, diagnosing, and treating one of the most discussed yet little-understood health conditions: leaky gut syndrome.

Do you have a leaky gut? For 80% of the population the answer is “yes”—and most people don’t even realize it. Leaky gut syndrome is the root cause of a litany of ailments, including: chronic inflammation, allergies, autoimmune diseases, hypothyroidism, adrenal fatigue, diabetes, and even arthritis.

To keep us in good health, our gut relies on maintaining a symbiotic relationship with trillions of microorganisms that live in our digestive tract. When our digestive system is out of whack, serious health problems can manifest and our intestinal walls can develop microscopic holes, allowing undigested food particles, bacteria, and toxins to seep into the bloodstream. This condition is known as leaky gut syndrome.

In Eat Dirt, Dr. Josh Axe explains that what we regard as modern “improvements” to our food supply—including refrigeration, sanitation, and modified grains—have damaged our intestinal health. In fact, the same organisms in soil that allow plants and animals to flourish are the ones we need for gut health. In Eat Dirt, Dr. Axe explains that it’s essential to get a little “dirty” in our daily lives in order to support our gut bacteria and prevent leaky gut syndrome. Dr. Axe offers simple ways to get these needed microbes, from incorporating local honey and bee pollen into your diet to forgoing hand sanitizers and even ingesting a little probiotic-rich soil.

Because leaky gut manifests differently in every individual, Dr. Axe also identifies the five main “gut types” and offers customizable plans—including diet, supplement, and lifestyle recommendations—to dramatically improve gut health in just thirty days. With a simple diet plan, recipes, and practical advice, Eat Dirt will help readers restore gut health and eliminate leaky gut for good.


Is chronic low back pain an infection?

Recently, there has been both immense interest and controversy regarding a randomised, controlled trial which showed antibiotics to be effective in the treatment of chronic low back pain (disc herniation with Modic Type 1 change). While this research has the potential to result in a paradigm shift in the treatment of low back pain, several questions remain unanswered. This systematic review aims to address these questions by examining the role of bacteria in low back pain and the relationship between bacteria and Modic change.

We conducted electronic searches of MEDLINE and EMBASE and included studies that examined the relationship between bacteria and back pain or Modic change. Studies were rated based on their methodological quality, a best-evidence synthesis was used to summarise the results, and Bradford Hill's criteria were used to assess the evidence for causation.

Eleven studies were identified. The median (range) age and percentage of female participants was 44.7 (41-46.4) years and 41.5% (27-59%), respectively, and in 7 of the 11 studies participants were diagnosed with disc herniation. Nine studies examined the presence of bacteria in spinal disc material and all identified bacteria, with the pooled estimate of the proportion with positive samples being 34%. Propionibacterium acnes was the most prevalent bacteria, being present in 7 of the 9 studies, with median (minimum, maximum) 45.0% (0-86.0) of samples positive. The best evidence synthesis found moderate evidence for a relationship between the presence of bacteria and both low back pain with disc herniation and Modic Type 1 change with disc herniation. There was modest evidence for a cause-effect relationship.

We found that bacteria were common in the spinal disc material of people undergoing spinal surgery. There was moderate evidence for a relationship between the presence of bacteria and both low back pain with disc herniation and Modic Type 1 change associated with disc herniation and modest evidence for causation. However, further work is needed to determine whether these organisms are a result of contamination or represent low grade infection of the spine which contributes to chronic low back pain.

Modic type 1 changes/bone edema in the vertebrae are present in 6 % of the general population and 35-40 % of the low back pain population. It is strongly associated with low back pain. The aim was to test the efficacy of antibiotic treatment in patients with chronic low back pain (>6 months) and Modic type 1 changes (bone edema).

The study was a double-blind RCT with 162 patients whose only known illness was chronic LBP of greater than 6 months duration occurring after a previous disc herniation and who also had bone edema demonstrated as Modic type 1 changes in the vertebrae adjacent to the previous herniation. Patients were randomized to either 100 days of antibiotic treatment (Bioclavid) or placebo and were blindly evaluated at baseline, end of treatment and at 1-year follow-up.

Primary outcome, disease-specific disability, lumbar pain. Secondary outcome leg pain, number of hours with pain last 4 weeks, global perceived health, EQ-5D thermometer, days with sick leave, bothersomeness, constant pain, magnetic resonance image (MRI).

144 of the 162 original patients were evaluated at 1-year follow-up. The two groups were similar at baseline. The antibiotic group improved highly statistically significantly on all outcome measures and improvement continued from 100 days follow-up until 1-year follow-up. At baseline, 100 days follow-up, 1-year follow-up the disease-specific disability-RMDQ changed: antibiotic 15, 11, 5.7; placebo 15, 14, 14. Leg pain: antibiotics 5.3, 3.0, 1.4; placebo 4.0, 4.3, 4.3. Lumbar pain: antibiotics 6.7, 5.0, 3.7; placebo 6.3, 6.3, 6.3. For the outcome measures, where a clinically important effect size was defined, improvements exceeded the thresholds, and a trend towards a dose-response relationship with double dose antibiotics being more efficacious.

The antibiotic protocol in this study was significantly more effective for this group of patients (CLBP associated with Modic I) than placebo in all the primary and secondary outcomes.

Sunday, April 24, 2016

Vitamin D treatment for psoriasis?

Psoriasis is a common, inflammatory, chronic, relapsing skin disease. Despite several hypotheses having been postulated to explain the pathogenesis of this disorder, nowadays it is considered as a T-cell-mediated disease; in this context an important role is played by vitamin D. The role of this micronutrient is important for many reasons: it is able to modulate the immune system; it is implicated in keratinocyte turnover; and it is involved in the integrity of the cutaneous barrier. In psoriasis, this molecule plays an important role due to its ability in the modulation of innate and adaptive immunity and by its antiproliferative and pro-differentiative effects on keratinocytes. Alteration of the metabolism of vitamin D may alter the cutaneous barrier integrity and favor an infective and inflammatory condition. The importance of vitamin D in the pathogenesis of psoriasis is not a mere mental exercise but may open further perspectives in the treatment of this disorder just preventing alterations of immune homeostasis, modulating the proliferation of keratinocyte, regulating the microbial flora and the response of the host to infective diseases.

J Dermatol. 2016 Mar 12. doi: 10.1111/1346-8138.13305. [Epub ahead of print]

Cochrane Database Syst Rev. 2016 Feb 26;2:CD009687. doi: 10.1002/14651858.CD009687.pub2.

Common over-the-counter drugs can hurt your brain

From allergies to insomnia, there's a pill for just about every problem. The problem is, those pills often come with a lengthy list of potential side effects.

And in the quest to cure what ails us as quickly as possible, those warnings are too often overlooked.
A new study, published Monday, offers the most definite proof yet of what scientists have known for at least a decade: that anticholinergic drugs (PDF) are linked with cognitive impairment and an increased risk of dementia.

Though you may have never heard of this class of drug, you've certainly heard of the medications themselves, including Benadryl, Demerol, Dimetapp, Dramamine, Paxil, Unisom and VESIcare. They are sold over the counter and by prescription as sleep aids and for chronic diseases including hypertension, cardiovascular disease and chronic obstructive pulmonary disease (COPD).

The new study is the first to examine the physical changes that serve as the catalyst for cognitive decline. Using brain imaging techniques, researchers at the Indiana University School of Medicine found (PDF) lower metabolism and reduced brain sizes among study participants taking anticholinergic drugs.

"These findings provide us with a much better understanding of how this class of drugs may act upon the brain in ways that might raise the risk of cognitive impairment and dementia," said Shannon Risacher, an assistant professor of radiology and imaging sciences.

The study looked at 451 people, with an average age of 73. Sixty of them were taking at least one medication with medium or high anticholinergic activity. To identify physical and physiological changes that could be associated with the reported effects, researchers assessed the results of memory and cognitive tests; PET scans, to measure brain metabolism; and MRI scans, to assess brain structure.

The cognitive tests revealed that people taking anticholinergic drugs performed worse on short-term memory tests, as well as on some tests of executive function, including verbal reasoning, planning and problem-solving.

Anticholinergic drug users also showed lower levels of glucose metabolism -- a biomarker for brain activity -- both in the brain overall and in the hippocampus, a region of the brain associated with memory and which has been identified as affected early by Alzheimer's disease. The participants using anticholinergic drugs were also found to have reduced brain volume and larger ventricles, the cavities inside the brain.


MammaPrint Shows Which Breast Cancer Patients Can Skip Chemo

A huge European trial has shown that the 70-gene assay MammaPrint can identify patients with early breast cancer who can safely skip adjuvant chemotherapy, even if they have clinical characteristics suggesting they are at high risk.

Results from this academic trial have been eagerly awaited since the trial began in 2007.

Known as MINDACT (Microarray for Node-Negative Disease May Avoid Chemotherapy Trial), the study involved 6693 patients across nine European countries.

It cost around €47 million (US$53 million), with funding provided by the European Organisation for Research and Treatment of Cancer (EORTC) Charitable Trust.

Outcome data, with a median follow-up of 5 years, were reported for the first time here at the American Association for Cancer Research 2016 Annual Meeting.

The women taking part in this trial had early-stage breast cancer and had undergone surgery. For the total trial population, the results show that using the genomic assay resulted in a 14% reduction in chemotherapy use versus assessment by clinical features of disease.

But the results were even more striking for a subgroup of patients, who were classed as high risk on clinical assessment. In these patients, use of the genomic assay is associated with a 46% reduction in chemotherapy prescription.

"The MINDACT trial results provide level 1A evidence that using MammaPrint could change clinical practice by substantially de-escalating the use of adjuvant chemotherapy and sparing many patients an aggressive treatment they will not benefit from," said principal investigator Martine Piccart, MD, PhD, head of the Department of Medicine at the Jules Bordet Institute in Brussels, and cofounder and chair of the Breast International Group (BIG).


Forget the gym - GARDENING is the best way to get in shape

Forget the gym - GARDENING is the best way to get in shape because you're more likely to stick to it

Take off your running shoes and slip on your wellies, because doctors say taking up gardening is just as good as going to the gym.

Half an hour of digging burns 150 calories, the same period raking a lawn burns 120 and pushing a lawn mower for 30 minutes burns 165.

While running may use up slightly more calories - about 240 for a half an hour jog - doctors are increasingly trying to encourage people to take up lighter activities that they will can weave into their daily routine.

Many people are intimidated by gyms and strenuous fitness programmes, and experts are instead shifting their focus to get people to build in more moderate exercise that they will not give up on.

Researchers have found that undertaking regular moderate exercise such as walking or gardening slashes the risk of a heart attack by half, and adds up to seven years to the average life span.

Professor Naveed Sattar, expert in metabolic medicine at Glasgow University, said: ‘Gardening is great - it gets you outside, it helps build muscle and it burns calories.

‘The key thing is sustainability. The way to keep exercising is to something you love - such as gardening - or do something for a reason, such as walking or cycling to work.’

The NHS advises that people do 150 minutes of moderate exercise a week, such as walking or gardening, or 75 minutes of strenuous exercise such as running or playing football.

But four out of five Britons fail to achieve the target, fuelling an epidemic of obesity and diabetes.


Americans Should Know What's in Their Soap and Shampoo

You may be happy to know that the U.S. Food and Drug Administration (FDA) prohibits the use of mercury, chloroform and nine other substances in your shampoo, soap and other personal care products.

That is, until you learn that the European Union prohibits the use of more than 1,300 substances in their personal care products.

The FDA's paltry restriction of just 11 substances is even more ridiculous considering there are nearly 13,000 chemicals used in cosmetics, and only about 10 percent have been evaluated for safety.

Although the FDA has the authority to regulate harmful ingredients in cosmetics and personal care products, it typically doesn't, preferring instead to rely on the products' manufacturers to regulate themselves.

If customers claim that a product has caused them harm, however, the companies are not required to report such claims to the FDA. And in the event that a product is deemed to be harmful, the FDA can't even order a recall.1

Do You Know What's in Your Shampoo?

It's a simple enough question, but chances are you have no idea what's lurking in your shampoo. Even if you read the label, you probably won't recognize most of the ingredients. The fact is if you use common commercial shampoos, you're lathering up your scalp with chemicals with every wash.

Several years back many people were shocked to learn that even Johnson & Johnson's baby shampoo contained toxic chemicals like formaldehyde and 1,4-dioxane.

In response to consumer demand, in 2012 Johnson & Johnson agreed to remove some of the toxic chemicals from their products (and reportedly took formaldehyde and 1,4-dioxane out of their personal care products as of 2015).2 However, many questionable chemicals still exist in popular shampoos.

Shampoo commonly contains endocrine disruptors, for instance, which are chemicals known to interfere with development and reproduction, and they may cause serious neurological and immune system effects. What else might be in your shampoo?

• Sodium lauryl sulfate, a surfactant, detergent and emulsifier used in thousands of cosmetic products, as well as in industrial cleaners.

It's present in nearly all shampoos, scalp treatments, hair color and bleaching agents, toothpastes, body washes and cleansers, make-up foundations, liquid hand soaps, laundry detergents, and bath oils/bath salts.

The real problem with SLES/SLS is that the manufacturing process (ethoxylation) results in SLES/SLS being contaminated with 1,4 dioxane, a carcinogenic byproduct.

• Phthalates are plasticizing ingredients that have been linked to birth defects in the reproductive system of boys and lower sperm-motility in adult men, among other problems. Be aware that phthalates are often hidden on shampoo labels under the generic term "fragrance."

• Methylisothiazolinone (MIT), a chemical used in shampoo to prevent bacteria from developing, which may have detrimental effects on your nervous system.

• Parabens, chemicals found in shampoo, deodorants and other cosmetics, have been shown to mimic the action of the female hormone estrogen, which can drive the growth of human breast tumors.

A study published in 2012 suggested that parabens from antiperspirants and other cosmetics indeed appear to increase your risk of breast cancer.3

The research looked at where breast tumors were appearing and determined that higher concentrations of parabens were found in the upper quadrants of the breast and axillary area, where antiperspirants are usually applied.


If meaningful use is a great idea, why isn’t it employed more widely?

A decade ago, electronic health records were aggressively promoted for a number of reasons. Proponents claimed that they would facilitate the sharing of health information, reduce error rates in health care, increase health care efficiency, and lower costs. Enthusiasts included the technology companies, consultants, and IT specialists who stood to reap substantial financial rewards from a system-wide switch to electronic records.

Even some health professionals shared in the enthusiasm.  Compared to the three-ring-binders that once held the medical records of many hospitalized patients, electronic records would reduce errors attributable to poor penmanship, improve the speed with which health professionals could access information, and serve as searchable information repositories, enabling new breakthroughs through the mining of “big data.”

To promote the transition to electronic records, the federal government launched what it called its meaningful use program, a system of financial rewards and penalties intended to ensure that patients would benefit.  Naturally, this raised an important question: If digitizing health records was such a good idea, why did the federal government need to impose penalties for health professionals who failed to adopt them?  Perhaps electronic health records were not so self-evidently beneficial as proponents suggested.

Despite the availability of $35 billion of federal funding to incentivize the adoption of this new health information technology, results have been disappointing.  For one thing, physicians, nurses, and other health professionals who rely on such systems on a daily basis reported steadily decreasing levels of satisfaction with them.  The move to electronic records has not only failed to enhance patient care but in many cases actually interfered with it.

For example, the requirement to populate the health care record with data, often motivated less by the needs of the patient than payment protocols, often draws the health professional’s attention away from patients.  Instead of increasing health professionals’ effectiveness and efficiency, too often such systems end up functioning as a distraction, keeping physicians’ and nurses’ eyes glued to a computer screen instead of the people they are caring for.

Far from increasing efficiency, many physicians find that electronic health records have slowed them down.  Faced with such tradeoffs, some simply give in, glumly allowing their gaze to shift from patients to computers.  Others extra spend extra hours on evenings and weekends attempting to tick off all the boxes.  Still others have chosen to hire “scribes,” whose job is to fill out the forms; a paradoxical situation in which enhanced efficiency has led to the hiring of additional personnel.

A related barrier to adoption was always the substantial cost of implementation.  In the short term, the productivity of health professionals suffered, as they struggled to learn complicated new systems.  Unfortunately, many of these costs turned out not to be temporary, inflicting ongoing losses in productivity and quality of care.  The same could be said for the professional satisfaction of many health professionals, who felt as though they had been transformed into data entry specialists.

As a result, the principal point of contact between health professionals and the hospitals and health systems they work for has shifted further and further away from the needs of patients.  We are producing more health care data than ever before, but much of this information is both irrelevant and difficult to access.  Really relevant clinical knowledge has been watered down by data that exist purely for purposes of documentation, regulation, and payment.

One disastrous misconception underlying electronic health record systems is the notion that documenting health care somehow improves it.  In practice, this has led physicians and nurses to spend more and more time documenting instead of doing, without good evidence that it is helping patients.  Just because an action is documented does not make it either real or beneficial.  In many cases, the burdens of documentation have turned out to outweigh its benefits.


Folate status and aberrant DNA methylation are associated with HPV infection and cervical pathogenesis

Aberrant DNA methylation is a recognized feature of human cancers, and folate is directly involved in DNA methylation via one-carbon metabolism. Previous reports also suggest that folate status is associated with the natural history of human papillomavirus (HPV) infection. A cross-sectional study was conducted to test the hypothesis that folate status and aberrant DNA methylation show a progressive change across stages of cervical pathology from normal cells to cervical cancer. Additionally, we postulated that a gene-specific hypermethylation profile might be used as a predictive biomarker of cervical cancer risk. DNA hypermethylation of seven tumor suppressor genes, global DNA hypomethylation, systemic folate status, and HPV status were measured in 308 women with a diagnosis of normal cervix (n = 58), low-grade cervical intraepithelial neoplasia (CIN1; n = 68), high-grade cervical intraepithelial neoplasia (CIN2, n = 56; and CIN3, n = 76), or invasive cervical cancer (ICC; n = 50). Lower folate status was associated with high-risk HPV infection (P = 0.031) and with a diagnosis of cervical intraepithelial neoplasia or invasive cervical cancer (P < 0.05). Global DNA hypomethylation was greater in women with invasive cervical cancer than all other groups (P < 0.05). A cluster of three tumor suppressor genes, CDH1, DAPK, and HIC1, displayed a significantly increased frequency of promoter methylation with progressively more severe cervical neoplasia (P < 0.05). These findings are compatible with a role for folate in modulating the risk of cervical cancer, possibly through an influence over high-risk HPV infection. DAPK, CDH1, and HIC1 genes are potential biomarkers of cervical cancer risk.


Melatonin in Chronic Pain Syndromes

Melatonin is a neurohormone secreted by epiphysis and extrapineal structures. It performs several functions including chronobiotic, antioxidant, oncostatic, immune modulating, normothermal, and anxiolytic functions. Melatonin affects the cardiovascular system and gastrointestinal tract, participates in reproduction and metabolism, and body mass regulation. Moreover, recent studies have demonstrated melatonin efficacy in relation to pain syndromes. The present paper reviews the studies on melatonin use in fibromyalgia, headaches, irritable bowel syndrome, chronic back pain, and rheumatoid arthritis. The paper discusses the possible mechanisms of melatonin analgesic properties. On one hand, circadian rhythms normalization results in sleep improvement, which is inevitably disordered in chronic pain syndromes, and activation of melatonin adaptive capabilities. On the other hand, there is evidence of melatonin-independent analgesic effect involving melatonin receptors and several neurotransmitter systems.


Children Have a 90 Percent Less Chance of Eczema If Parents Suck On Pacifiers Rather Than Wash or Boil Them

OBJECTIVE: Immune stimulation through exposure to commensal microbes may protect against allergy development. Oral microbes may be transferred from parents to infants via pacifiers. We investigated whether pacifier cleaning practices affected the risk of allergy development.

METHODS: A birth-cohort of 184 infants was examined for clinical allergy and sensitization to airborne and food allergens at 18 and 36 months of age and, in addition, promptly on occurrence of symptoms. Pacifier use and pacifier cleaning practices were recorded during interviews with the parents when the children were 6 months old. The oral microbiota of the infants was characterized by analysis of saliva samples collected at 4 months of age.

RESULTS: Children whose parents “cleaned” their pacifier by sucking it (n = 65) were less likely to have asthma (odds ratio [OR] 0.12; 95% confidence interval [CI] 0.01–0.99), eczema (OR 0.37; 95% CI 0.15–0.91), and sensitization (OR 0.37; 95% CI 0.10–1.27) at 18 months of age than children whose parents did not use this cleaning technique (n = 58). Protection against eczema remained at age 36 months (hazard ratio 0.51; P = .04). Vaginal delivery and parental pacifier sucking yielded independent and additive protective effects against eczema development. The salivary microbiota differed between children whose parents cleaned their pacifier by sucking it and children whose parents did not use this practice.

CONCLUSIONS: Parental sucking of their infant’s pacifier may reduce the risk of allergy development, possibly via immune stimulation by microbes transferred to the infant via the parent’s saliva.


Investment groups across to restaurants: stop adding antibiotics to the meat

A coalition of powerful investment firms who manage a combined $1 trillion in assets has sent letters to top restaurant chains in the U.S. and U.K. urging them to stop using antibiotics in their poultry and meat.

As reported by Healthline:

"The Farm Animal Investment Risk & Return (FAIRR), an initiative of Coller Capital that combines 53 other investment groups, announced this week they've sent letters to some of the biggest restaurant chains in the U.S. and the U.K.

"The chains include McDonald's, Wendy's, Domino's, Chili's, Olive Garden, Burger King, Tim Hortons, KFC, Pizza Hut, and Taco Bell, among others.

"Jeremy Coller, founder of the FAIRR Initiative and chief investment officer of Coller Capital, said these large food companies are 'key ingredients' in the portfolios of most of their pensions and savings. He said asking how these companies plan to meet the challenge of reducing antibiotic use is a matter of proper risk management."

These investors are savvy enough to anticipate the future, unlike the many major restaurant chains that still source from suppliers who use antibiotics in the raising of animals for meat to be consumed by humans.

"The world is changing, regulation on antibiotic use is set to tighten, and consumer preferences are shifting away from factory farmed food," Coller said. "As stewards of these food companies and responsible investors, we want to protect both human health and shareholder value."


What can physicians learn from a veterinarian?

In short ... a lot.

Dr. Joel Wallach's research has resulted in the publication of more than 70 peer reviewed and refereed journal articles in the fields of nutrition and pharmaceutical research, and he has made major contributions to eight multi-authored text and reference books on these subjects.  He obtained a Bachelor of Science in Agriculture from the University of Missouri in 1962, with a major in Animal Husbandry (Nutrition) and a minor in Field Crops and Soils. In 1964 he was awarded a Doctorate in Veterinary Medicine (D.V.M.), also from the University of Missouri. Thereafter, he completed a three-year (1965-68) post-doctoral fellowship at The Center for the Biology of Natural Systems at Washington University in St. Louis, Missouri. In 1982 he obtained a Doctorate in Naturopathic Medicine (N.D.) from the National College of Naturopathic Medicine in Portland, Oregon.

Essential Nutrients

60 Minerals
Calcium, Magnesium, Phosphorus,  Potassium, Sodium, Chloride, Sulfur, Cobalt, Copper, Aluminum, Arsenic, Barium, Beryllium, Boron, Bromine, Carbon, Iodine, Iron, Manganese, Selenium, Zinc, Cerium, Cesium, Chromium, Dysprosium, Erbium, Europium, Gadolinium, Gallium, Germanium, Gold, Hafnium, Holmium, Hydrogen, Lanthanum, Lithium, Lutetium, Molybdenum, Neodymium, Nickel, Niobium, Nitrogen, Oxygen, Praseodymium, Rhenium, Rubidium, Samarium, Scandium, Silica, Silver, Strontium, Tantalum, Terbium, Thulium, Tin, Titanium, Vanadium, Ytterbium, Yttrium, Zirconium

2-3 Essential Fatty Acids
Omega 3, Omega 6, Omega 9

16 Vitamins
Vitamin A, Vitamin B1, Vitamin B2, Vitamin B3, Vitamin B5, Vitamin B6, Vitamin B12, Vitamin C, Vitamin D, Vitamin K, Biotin, Choline, Flavonoids (Bioflavonoids), Folic Acid, Inositol

12 Amino Acids
Valine, Lysine, Threonine, Leucine, Isoleucine, Tryptophan, Phenylalanine, Methionine, Histidine, Arginine, Taurine, Tyrosine

Sunday, April 17, 2016

Olive Leaf Extract

~~ Along the bank of the river, on this side and that, will grow all kinds of trees used for food. Their leaves will not wither, and their fruit will not fail. They will bear fruit every month because their water flows from the sanctuary. Their fruit will be for food, and their leaves for healing. Ez 47:12 ~~

Physicians are notorious for the dismissive line: "There's no evidence for that natural therapy!" I heard this today from a physician (an orthopedic surgeon) about the use of olive leaf extract. Unfortunately, this statement most often is a reflection of their own lack of knowledge of the scientific literature and over-reliance on summary articles for their information.

In terms of olive leaf extract ... go to PubMed. Type "oleuropein" which is one the main active ingredients of olive leafs and click on "Clinical Trials". As of the time of writing of this article, there are 580 clinical trials involving this olive leaf extract.



Effects of the olive-derived polyphenol oleuropein on human health.
Int J Mol Sci. 2014 Oct 14;15(10):18508-24. doi: 10.3390/ijms151018508.

The use of the products derived from the olive tree on human health dates back centuries. In several civilizations, the olive tree had and still has a very strong cultural and religious symbolism. Notably, the official seal and emblem of the World Health Organization features the rod of Asclepius over a world map surrounded by olive tree branches, chosen as a symbol of peace and health. Recently, accumulating experimental, clinical and epidemiological data have provided support to the traditional beliefs of the beneficial effect provided by olive derivates. In particular, the polyphenols present in olive leaves, olives, virgin (unrefined) olive oil and olive mill waste are potent antioxidant and radical scavengers with anti-tumor and anti-inflammatory properties. Here, we review the positive impact on human health of oleuropein, the most prevalent polyphenol present in olives. In addition, we provide data collected in our laboratory on the role of oleuropein in counteracting lipid accumulation in a mouse model of non-alcoholic fatty liver disease.


Memorial Sloan Kettering Cancer Center - Integrative Medicine

Derived from the olive plant, both leaves and the extract have been used to treat infections, inflammation, diabetes, and hypertension. A major component of olive leaf, oleuropein, has antioxidant properties (1). Because of its hypoglycemic effects, the leaf extract can induce insulin release and improve peripheral uptake of glucose (2). Further, the leaf extracts demonstrated antimicrobial properties (3) (22), anti-HIV (4), and anticancer (13) (14) (15) (18) (19) properties. Animal studies showed antiarrhythmic, spasmolytic, diuretic (5), antihypertensive (6), analgesic (20) (21), and cholesterol-lowering (7) effects.

Small studies have shown effectiveness of olive leaf extract in reducing blood pressure in patients with hypertension (16) (17). The anticancer effects of olive leaf extract in humans are not known.


  1. Montilla MP, Agil A, Navarro MC, Jimenez MI, Garcia-Granados A, Parra A et al. Antioxidant activity of maslinic acid, a triterpene derivative obtained from Olea europaea. Planta Med 2003;69:472-4.
  2. Gonzalez M, Zarzuelo A, Gamez MJ, Utrilla MP, Jimenez J, Osuna I. Hypoglycemic activity of olive leaf. Planta Med 1992;58:513-5.
  3. Markin D, Duek L, Berdicevsky I. In vitro antimicrobial activity of olive leaves. Mycoses 2003;46:132-6.
  4. Lee-Huang S, Zhang L, Huang PL, Chang YT, Huang PL. Anti-HIV activity of olive leaf extract (OLE) and modulation of host cell gene expression by HIV-1 infection and OLE treatment. Biochem.Biophys.Res Commun. 2003;307:1029-37.
  5. PDR for Herbal Medicines. Montvale, NJ: Medical Economics, 1998.
  6. Somova LI, Shode FO, Ramnanan P, Nadar A. Antihypertensive, antiatherosclerotic and antioxidant activity of triterpenoids isolated from Olea europaea, subspecies africana leaves. Journal of Ethnopharmacology.Vol.84(2-3)()(pp 299-305), 2003. 2003;299-305.
  7. Pasquale RD, Monforte A, Trozzi A, Raccuia S, Tommasini S, Ragusa S. Effects of leaves and shoot of Olea europaea L. and oleuropien on experimental hypercholesterolemia in rat. Plantes Med Phytother 1991;25:134-40.
  8. Horn C. Olive leaf to fight infection. Natural Health 2000;30:40.
  9. Zarzuelo A, Duarte J, Jimenez J, Gonzalez M, Utrilla MP. Vasodilator effect of olive leaf. Planta Med 1991;57:417-9.
  10. Pieroni A, Heimler D, Pieters L, van Poel B, Vlietinck AJ. In vitro anti-complementary activity of flavonoids from olive (Olea europaea L.) leaves. Pharmazie 1996;51:765-8.
  11. Brinker F. Herb Contraindications And Drug Interactions. Sandy, OR: Eclectic Medical Publications, 2001.
  12. Liccardi G, D’Amato M, D’Amato G. Oleaceae pollinosis: a review. Int Arch.Allergy Immunol. 1996;111:210-7.
  13. Kimura Y, Sumiyoshi M. Olive leaf extract and its main component oleuropein prevent chronic ultraviolet B radiation-induced skin damage and carcinogenesis in hairless mice. J Nutr. 2009 Nov;139(11):2079-86.
  14. Anter J, Fernández-Bedmar Z, Villatoro-Pulido M, et al. A pilot study on the DNA-protective, cytotoxic, and apoptosis-inducing properties of olive-leaf extracts. Mutat Res. 2011 May 20. [Epub ahead of print].
  15. Mijatovic SA, Timotijevic GS, Miljkovic DM, et al. Multiple antimelanoma potential of dry olive leaf extract. Int J Cancer. 2011 Apr 15;128(8):1955-65.
  16. Perrinjaquet-Moccetti T, Busjahn A, Schmidlin C, et al. Food supplementation with an olive (Olea europaea L.) leaf extract reduces blood pressure in borderline hypertensive monozygotic twins. Phytother Res. 2008 Sep;22(9):1239-42.
  17. Susalit E, Agus N, Effendi I, et al. Olive (Olea europaea) leaf extract effective in patients with stage-1 hypertension: comparison with Captopril. Phytomedicine. 2011 Feb 15;18(4):251-8.
  18. Abaza L, Talorete TP, Yamada P, et al. Induction of growth inhibition and differentiation of human leukemia HL-60 cells by a Tunisian gerboui olive leaf extract. Biosci Biotechnol Biochem. 2007 May;71(5):1306-12.
  19. Anter J, Fernández-Bedmar Z, Villatoro-Pulido M, et a. A pilot study on the DNA-protective, cytotoxic, and apoptosis-inducing properties of olive-leaf extracts. Mutat Res. 2011 Aug 16;723(2):165-70.
  20. Kaeidi A, Esmaeili-Mahani S, Sheibani V, et al. Olive (Olea europaea L.) leaf extract attenuates early diabetic neuropathic pain through prevention of high glucose-induced apoptosis: in vitro and in vivo studies. J Ethnopharmacol. 2011 Jun 14;136(1):188-96.
  21. Esmaeili-Mahani S, Rezaeezadeh-Roukerd M, Esmaeilpour K, et al. Olive (Olea europaea L.) leaf extract elicits antinociceptive activity, potentiates morphine analgesia and suppresses morphine hyperalgesia in rats. J Ethnopharmacol. 2010 Oct 28;132(1):200-5.
  22. Pereira AP, Ferreira IC, Marcelino F, et al. Phenolic compounds and antimicrobial activity of olive (Olea europaea L. Cv. Cobrançosa) leaves. Molecules. 2007 May 26;12(5):1153-62.

Here is another set of references:

1. Aziz NH, Farag SE, Mousa LA, Abo-Zaid MA. Comparative antibacterial and antifungal effects of some phenolic compounds. Microbios. 1998;93:43–54.

2. Bisignano G, Tomaino A, Lo Cascio R, Crisafi G, Uccella N, Saija A. On the in-vitro antimicrobial activity of oleuropein and hydroxytyrosol. J Pharm Pharmacol. 1999;51:971–4.

3. Elliott GA, Buthala DA, DeYoung EN. Preliminary safety studies with calcium elenolate, an antiviral agent. Antimicrobial Agents Chemother. 1969;9:173–6.

4. Fleming HP, Walter WM Jr, Etchells JL. Antimicrobial properties of oleuropein and products of its hydrolysis from green olives. Appl Microbiol. 1973;26:777–82.

5. Heinze JE, Hale AH, Carl PL. Specificity of the antiviral agent calcium elenolate. Antimicrob Agents Chemother. 1975;8:421–5.

6. Hirschman SZ. Inactivation of DNA polymerases of murine leukaemia viruses by calcium elenolate. Nat New Biol. 1972;238:277–9.

7. Juven B, Henis Y, Jacoby B. Studies on the mechanism of the antimicrobial action of oleuropein. J Appl Bacteriol. 1972;35:559–67.

8. Lee-Huang S, Zhang L, Huang PL, Chang YT, Huang PL. Anti-HIV activity of olive leaf extract (OLE) and modulation of host cell gene expression by HIV-1 infection and OLE treatment. Biochem Biophys Res Commun. 2003;307:1029–37.

9. Renis HE. Inactivation of myxoviruses by calcium elenolate. Antimicrob Agents Chemother. 1975;8:194–9.

10. Renis HE. In vitro antiviral activity of calcium elenolate. Antimicrobial Agents Chemother. 1969;9:167–72.

11. Walter WM Jr, Fleming HP, Etchells JL. Preparation of antimicrobial compounds by hydrolysis of oleuropein from green olives. Appl Microbiol. 1973;26:773–6.

12. Cherif S, Rahal N, Haouala M, et al.A clinical trial of a titrated Olea extract in the treatment of essential arterial hypertension. J Pharm Belg. 1996;51:69–71.

13. Fehri B, Aiache JM, Memmi A, Korbi S, Yacoubi MT, Mrad S, Lamaison JL. Hypotension, hypoglycemia and hypouricemia recorded after repeated administration of aqueous leaf extract of Olea europaea L. J Pharm Belg. 1994;49:101–8.

14. Khayyal MT, el-Ghazaly MA, Abdallah DM, Nassar NN, Okpanyi SN, Kreuter MH. Blood pressure lowering effect of an olive leaf extract ( Olea europaea) in L-NAME induced hypertension in rats. Arzneimittelforschung. 2002;52:797–802.

15. Ribeiro Rde A, Fiuza de Melo MM, De Barros F, Gomes C, Trolin G. Acute antihypertensive effect in conscious rats produced by some medicinal plants used in the state of Sao Paulo. J Ethnopharmacol. 1986;15:261–9.

16. Zarzuelo A, Duarte J, Jimenez J, Gonzalez M, Utrilla MP. Vasodilator effect of olive leaf. Planta Med. 1991;57:417–9.

17. Fehri B, Aiache JM, Memmi A, et al. Hypotension, hypoglycemia and hypouricemia recorded after repeated administration of aqueous leaf extract of Olea europaea L [in French]. J Pharm Belg. 199449:101–8.

18. Gonzalez M, Zarzuelo A, Gamez MJ, Utrilla MP, Jimenez J, Osuna I. Hypoglycemic activity of olive leaf. PlantaMed. 1992;58:513–5.

19. Onderoglu S, Sozer S, Erbil KM, Ortac R, Lermioglu F. The evaluation of long-term effects of cinnamon bark and olive leaf on toxicity induced by streptozotocin administration to rats. J Pharm Pharmacol. 1999;51:1305–12.

20. Susalit E, Agus N, Effendi I, et al. Olive (Olea europaea) leaf extract effective in patients with stage-1 hypertension: comparison with Captopril. Phytomedicine. 2011;18(4):251-258.

The Diabetes Summit 2016

The Diabetes Summit 2016 is online and FREE from April 18-25, 2016.

At the 2015 Diabetes World Summit, we stated that 387 million people in the world have diabetes. Over a year later, that number is now 415 million — that’s the equivalent of every single resident of the U.S., Germany and Bolivia having diabetes. By 2040, the IDF predicts this will reach 642 million…

The 2016 Diabetes World Summit will help you understand and address:

  • The root causes of all forms of diabetes and how to address them
  • How to prevent and stop the progression of diabetes
  • 10 of the most important strategies to help reverse type 2 diabetes
  • The optimal diet to prevent, control and reverse type 2 diabetes
  • Most effective forms of exercise for optimal blood sugar control
  • Latest insights into understanding and correcting metabolic problems

Connections between mycotoxins, autoimmunity and gluten-sensitivity

Jill C. Carnahan, MD, ABFM, ABIHM, IFMCP

13:17 Mold Sensitivity Genes: LabCorp and Quest are Dr. Carnahan’s favored labs for HLA-DR Typing. The results need to be interpreted. Dr. Carnahan is able to do this with a Rosetta stone from Subject expert, Dr. Ritchie Shoemaker. There are two “dreaded” genotypes for mold sensitivity, 11-3-53 and 4-3-52. It's is estimated that 1% of the population has one of these two genes. Celiac HLAs are related to mold HLAs. It is the misprocessing of antigens.

14:49 HLAs, Pac Man of the Immune System: Dr. Carnahan orders Celiac HLA and HLA-DR typing for Celiac, and HLA-DR for mold, Lyme and other biotoxins. Celiac HLA typing, checks DQ2 and DQ8. People with two SNPs for DQ2, two SNPs of DQ8 or one DQ2 and one DQ8, have a high probability of problems with gluten processing. They may never get Celiac disease, but gluten can create inflammation and trigger autoimmunity. Autoimmunity and mold go hand-in-hand because of the inflammatory cascade.

19:50 The Possible Benefit of This Over-Reactive Immune System: Sometimes Dr. Carnahan has patients who say that they have not had a cold or flu for years. They may have some sort of virus, but their immune system is so dysfunctional that they are not symptomatic. Sometimes it is not the threat causing our illness, but our immune system’s response to the threat. People, who don’t have this cytokine reaction, are more prone to have these HLA types. Their immune system is so dysfunctional that it isn’t rallying a proper response.

21:31 Symptoms of Mold Exposure: Symptoms include fatigue, brain fog where you cannot concentrate, focus or complete a task easily, and memory issues in the form of finding words. NeuroQuant, SPECT MRI, or a functional MRI, all show changes in the brain from the mold. Instead of seasonal allergy responses, people with mold sensitivity have super-reactive mast cells and are in a constant histamine response with allergy symptoms. Your skin is a detox organ, so you might have new onset acne, sores, lesions, and/or scalp issues. Joint pain is common because it is an inflammatory response. Tingling, shortness of breath, sinus congestion, and blurry vision is also common.

24:12 Symptom – Prone to Static Shock: Mold affects the pituitary access to the extreme. One of the hormones in the posterior pituitary is antidiuretic hormone, which controls our saltwater balance, so another symptom is constant thirst that is unquenchable, dry skin, dry eyes,. The antidiuretic hormone is affected when MSH, another hormone that regulates the hypothalamic access. In mold illness, this almost always drops. That regulates cortisol, adrenals, thyroid, and antidiuretic hormone. Because antidiuretic hormone is low, you are drinking lots of water and have more salt on the surface of your skin. This makes you prone to static charge.

28:47 School Buildings Commonly Have Mold: Courthouses, schools and older buildings often have mold.
30:46 Biomarkers of Mold: The CRP or ESR inflammatory markers will be normal for those of us with mold reaction. CMP, basic metabolic kidney/liver, will be normal. CBC, most of the time will be normal. Routine labs will be normal. Because labs come back normal, many are deemed to have a psychiatric illness, especially when they experience another symptom of mold exposure, rage, anger and sudden deep dark depression when exposed to mold. Dr. Carnahan does HLA typing along with testing of leptin and adiponectin which will show early signs of insulin dysregulation. Mold reaction brings on insulin resistance. Dysregulation of cortisol blocks insulin from entering your cells. Your pancreas can be affected from the toxins, causing elevated lipase or amylase. You can have poor production of pancreatic enzymes and poor production of insulin. You can even become diabetic even when they have no family history.

32:51 Symptom - Sudden Weight Gain: People can put on 50 pounds from mold exposure even with decreased caloric intake and increased exercise. Because of the insulin resistance from the imbalance of leptin and adiponectin, these people cannot burn fat. They are metabolically so dysfunctional that typical dietary interventions do not work.

33:28 Mold and Blood Profusion: Mold exposure sensitivity decreases blood flow to your tissues. VEGF shows capillary tissue profusion. Early in the illness, this increases, causing new blood vessel growth. Dr. Carnahan, a runner, would have decreased profusion in her legs, causing lactic acid to build and sometimes her lower legs would go numb.

34:25 Mold Exposure Sensitivity and Autoimmunity: VEGF causes TGF Beta to rise. TGF Beta is a master puppeteer in the immune system that regulates autoimmunity, impactingTreg cells, and t17 cells. High TGF Beta suppresses Treg cells, decreases core antigen presentation, and affects MSH which effects cortisol, leptin, ADH and much more.


Friday, April 15, 2016

Adult Growth Hormone Deficiency

A person who has too little adult growth hormone will have symptoms that include:

  •     A higher level of body fat, especially around the waist
  •     Anxiety and depression
  •     Decreased sexual function and interest
  •     Fatigue
  •     Feelings of being isolated from other people
  •     Greater sensitivity to heat and cold
  •     Less muscle (lean body mass)
  •     Less strength, stamina and ability to exercise without taking a rest
  •     Reduced bone density and a tendency to have more bone fractures as they get older
  •     Changes in the make up of the blood cholesterol.

People with adult growth hormone deficiency have higher than normal levels of low-density lipoproteins in comparison to their high density lipoproteins. They also tend to have higher triglyceride levels. (Triglycerides are another type of fat that circulates in the blood and contributes to blocked blood vessels.)


High IGF-1 from dietary ingestion inhibits the hypothalamus through decreased GHRH and Somatostatin. Long-term effects of exogenous IGF-1 is suppression of endogenous growth hormone. So ... how much milk did you drink when milk was derived from rBGH or rBST treated cows?


Consumption of cow's milk and cow's milk protein result in changes of the hormonal axis of insulin, growth hormone and insulin-like growth factor-1(IGF-1) in humans. Milk consumption raises IGF-1 serum levels in the perinatal period, adolescence and adulthood. During puberty with the physiological onset of increased secretion of growth hormone, IGF-1 serum levels increase and are further enhanced by milk consumption. IGF-1 is a potent mitogen; after binding to its receptor in various tissues, it induces cell proliferation and inhibits apoptosis. Keratinocytes and sebocytes, as well as the androgen-synthesizing adrenals and gonads, are stimulated by IGF-1. The epidemic incidence of adolescent acne in Western milk-consuming societies can be explained by the increased insulin- and IGF-1-stimulation of sebaceous glands mediated by milk consumption. Acne can be regarded as a model for chronic Western diseases with pathologically increased IGF-1-stimulation. Many other organs, such as the thymus, bones, all glands, and vascular smooth muscle cells as well as neurons are subject to this abnormally increased hormonal stimulation. The milk-induced change of the IGF-1-axis most likely contributes to the development of fetal macrosomia, induction of atopy, accelerated linear growth, atherosclerosis, carcinogenesis and neurodegenerative diseases. Observations of molecular biology are supported by epidemiologic data and unmask milk consumption as a promoter of chronic diseases of Western societies.


Never-published data on vegetable oil and heart health reveals some disturbing trends

The American Heart Association, U.S. Dietary Guidelines and most doctors and nutritionists say that if you eat more “healthy fats” from vegetable and seed oils and less “bad fats” from red meat and dairy products, you’re on your way to better cardiovascular health.

It turns out that may not be supported by the highest standards of scientific evidence. A new analysis of never-before-published trial data from the 1960s and ‘70s pokes holes at the notion that we can stave off heart attack and stroke by eating more polyunsaturated fat (the “healthy” kind). Instead, it suggests that some people who eat more of this fat from vegetable and and seed oils — specifically, those that are high in omega-6 fatty acids — actually have a higher risk of death than those who have a diet high in saturated fat.

The study’s findings were never published in full, perhaps because they went against the emerging and increasingly popular hypothesis that saturated fat in foods like red meat and dairy causes cholesterol levels in blood to rise, increasing the risk of cardiovascular disease and death. This hypothesis, called the Lipid Hypothesis, is currently a generally accepted piece of conventional wisdom in the nutrition science community. With help from the son of one of the original investigators, two researchers recently unearthed and re-analyzed the previously unpublished data. What they found contradicts the Lipid Hypothesis, and could change the way we view “healthy” polyunsaturated fats.

The analysis, published Tuesday in the British medical journal BMJ, is a sequel of sorts for lead researchers Daisy Zamora of the University of North Carolina, Chapel Hill and Christopher Ramsden of the National Institutes of Health. Back in 2013, they performed a similar analysis on another set of previously unpublished data, known as the Sydney Diet Heart Study, and came to similar conclusions: Substituting saturated fat with oils high in omega-6 acids, also known as linoleic acids, actually increases the risk of death from all causes, coronary heart disease and cardiovascular disease.

“Our research highlights the paucity of evidence supporting the dietary replacement of saturated fat with vegetable oils rich in linoleic acid for heart health,” Zamora told The Huffington Post.

Experts say that, combined, these two trials could upend the way we view healthy eating — especially when it comes to our relationship with so-called “healthy” oils.

This new finding is based on data from 1968 

Back in 1968, the U.S. Public Health Service and National Heart Institute funded a five-year study called the Minnesota Coronary Experiment to see whether replacing saturated fat with vegetable oil would prevent heart attacks, stroke and death. To have complete control over what study participants ate and didn’t eat, researchers Ivan Frantz and Ancel Keys — who famously made the connection between a Mediterranean diet and better heart health — divided over 9,000 adults in nursing homes and mental hospitals into two groups in a double blind, randomized trial.

The intervention group reduced their saturated fat intake about 50 percent compared to their normal diet, and upped their vegetable oil intake more than 280 percent in the form of corn oil. The control group was put on a diet much lower in polyunsaturated fats and higher in saturated fat — in other words, more typical of the average American diet.

These experimental diets lasted between 41 to 56 months, depending on the institution. Then Frantz and Keys followed up with roughly 2,403 participants who stayed on their new diets for a year or more, and measured their cholesterol levels several times over an average of three years. They also conducted autopsies participants who died during the experiment to see whether there were any differences in their arterial or heart health at death.

The unexpected (and perhaps unwanted) results

Frantz and Keys found that the intervention group participants, who swapped more corn oil for saturated fat, did indeed lower the levels of cholesterol in their blood compared to the control group and baseline levels. The intervention worked as they predicted.

However, later analyses reported in a 1981 master’s thesis paper by now-retired biostatistician Steven K. Broste found that the though the intervention group lowered their cholesterol levels, they didn’t lower their risk of death. In fact, participants who were over 65 when they started the experiment actually had a higher risk of death if they had been part of the group eating more vegetable oils.

The autopsies Frantz and Keys conducted were even more disquieting. Among the 149 autopsies for which there was complete information, 41 percent of the intervention group showed signs of at least one heart attack, while only 22 percent of the participants in the control group — the high saturated fat group — showed the same. Deceased people from the intervention group also had similar levels of fatty plaque buildup in the arteries and hardened arteries compared to the control group.

After collecting all the data from the Minnesota trial, Zamora and Ramsden combined it with four published randomized, controlled trials that also substituted saturated fat with vegetable oils high in linoleic acid. Like the Minnesota trial, this additional meta-analysis found there was no benefit to switching to these oils when it came to death by coronary heart disease or death by any cause.

“It’s truly a shame that Americans are being recommended to consume these industrial seed oils, as it’s in direct contradiction to the highest level of evidence in the literature,” observed James DiNicolantonio, a cardiovascular research scientists at St. Luke’s Mid America Heart Institute who wasn’t involved in these studies.

For unknown reasons, Frantz and Keys never published the full results of this experiment. Their study has the distinction of being one of the very few randomized, controlled trials — considered the highest standard of medical evidence — to evaluate the effects of lowering saturated fat on heart health.

In their 2016 re-analysis, Zamora and Ramsden speculate that perhaps the researchers didn’t publish the findings in full because they were so “contrary” to the popular scientific beliefs of the time.

“There would have been little or no scientific or clinical trial literature at the time to support findings that were so contrary to prevailing beliefs and public policy,” they wrote. “And, finally, it is possible that medical journal reviewers would not have accepted study results for the reasons cited above.”

Some vegetable oils are better for you than others

It’s important to note that Frantz and Keys’ trial was conducted when Americans were eating more corn oil and margarine made from corn oil, and that corn oil was the only polyunsaturated fat that was used in the experiment. Corn oil is high in omega-6 fatty acids, and while our bodies need some amount of omega-6 fatty acids to function properly, Zamora and Ramsden note that too much of it could have a “wide range of biochemical consequences” that could perhaps be negative. This nuance isn’t reflected in the most up-to-date nutritional advice in the federal dietary guidelines, which state simply we should eat less saturated fat and more polyunsaturated fat without mention of omega-6 acids.

Rebecca Blake, a registered dietitian and administrative director for medicine at Mt. Sinai-Beth Israel, put it this way: “We don’t usually consider corn oil the gold standard of healthy oils.

“It’s fine — it’s a vegetable oil,” she continued. “But it’s not olive oil, and it’s not like having a diet that’s high in healthy fats like fatty fish.”

Some other sources of polyunsaturated fats, like fatty fish, contain both omega-6 and omega-3 fatty acids. It’s this combination that could be the key to protecting people’s hearts, rather than just consuming polyunsaturated fats as a class, notes Tom Brenna, a professor of human nutrition at Cornell University.

“This gives us strong reason to think carefully about the composition of polyunsaturated fatty acids,” said Brenna. “The analysis does not say that polyunsaturated fatty acids in general are a bad substitute, but that they’re seeing negative things exclusively with omega-6 fatty acids.”

He also expressed regret that nutrition experts have not been able to effectively communicate this to the general public. Brenna, who served on the committee of scientists who helped create the 2015-2020 U.S. Dietary Guidelines, says it isn’t as simple as rattling off the names of certain plant oils. Different types of oils have different fatty acid profiles, which all act on your body in different ways.

“You can no longer just say eat one kind of oil or another kind of oil,” he said. “You have to specify which one it is, and we have not, as a society, figured out how to talk about that yet.”

For the record, the only oils that Brenna can wholeheartedly recommend are olive oil, avocado oil and high-oleic sunflower oil.

“It gets so confusing for people, but it shouldn’t be,” Brenna concluded. “We should figure out a way to deal with this behind the scenes, so that people don’t have to become chemists in order to eat.”