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Textbooks will have to be rewritten with the recent discovery of a system of lymphatic vessels that are a direct link from the immune system to the brain. Amazing that after centuries of studying people, that only now was this system detected (but they are very small and they follow a major blood vessel down into the sinuses). After extensive research,  the researchers determined that these vessels carry both fluid and immune cells from the cerobrospinal fluid, and that they exist in humans. The discovery reinforces findings that immune cells are present even within healthy brains, a notion that was doubted until recently.From Medical Daily:

Discovery Of 'Missing Link' Between Brain And Immune System Could Change How Disease Is Studied

The recent discovery of a "missing link" between the brain and the immune system may lead to a complete revision of biology textbooks. The link, vessels of the lymphatic system that run through the sinuses, were previously unidentified and thought not to exist. However, the true significance of the discovery lies in the potential effects this finding could have on both the study and treatment of neurological diseases such as Alzheimer’s disease and multiple sclerosis.  

The newly discovered "central nervous system lymphatic system vessels" follow a major blood vessel down into the sinuses, an area that has been traditionally difficult to obtain images of. Their presence is causing a stir in the medical world, as the researchers responsible believe the vessels may help to explain current medical mysteries, such as why patients with Alzheimer’s disease have accumulations of large protein plaques in the brain.

The fascinating discovery was made by researchers at the University of Virginia School of Medicine, and a study on the finding is currently available in the online journal Nature....Using a recently developed method, the team mounted the meninges, the membranes covering the brain, on a single slide so that they could be better observed. Only after doing this were they able to notice the brain’s elusive lymphatic vessels.   "It's so close to the blood vessel, you just miss it," Kipnis said. "If you don't know what you're after, you just miss it."

The team believes that the “missing link” between the brain and the immune system could explain why some diseases like Alzheimer’s can cause plaque buildup in the brain. Kipnis believes this plaque may be the result of the meningeal lymphatic vessels not efficiently removing buildup before it reaches the brain. Although scientists are currently not sure what causes cell death and tissue loss in the brains of those with Alzheimer’s, this plaque buildup is believed to play a role.

It’s not just the presence of plaque in the brain that the researchers hope this discovery can shed light on. According to Kipnis, this discovery could completely change the way we perceive the neuro-immune interaction.“We believe that for every neurological disease that has an immune component to it, these vessels may play a major role,” Kipnis said. “Hard to imagine that these vessels would not be involved in a [neurological] disease with an immune component.”The vessels also appear to look different with age, which has lead the researchers to suggest that they may play a role in the aging process.

 

Maps of the lymphatic system: old (left) and updated to reflect UVA's discovery.   Credit: University of Virginia Health System

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Low levels of vitamin D are associated with low levels of testosterone in healthy middle-aged men. Note that hypovitaminosis D means low levels of vitamin D in the blood, defined by a lab test as "25-hydroxyvitamin D level below 30.0 ng/L. Interestingly, being overweight also seems to lower the testosterone level, and losing weight raises the level, and supplementing with vitamin D may raise the testosterone level in those with low levels (the German study mentioned in the article). And research with mice suggests that there is something about testosterone synthesis that needs vitamin D. From Medscape:

Low Vitamin D Tied to Testosterone Dip in Healthy Men

Low levels of vitamin D are significantly and independently associated with low levels of testosterone in otherwise healthy middle-aged men, according to a study presented at the American Urological Association 2015 Annual Meeting in New Orleans. 

In this new analysis of data from of the World Trade Center CHEST program, blood samples from 824 men were analyzed for various parameters, such as 25-hydroxyvitamin D and total testosterone. Hypovitaminosis D was defined as a 25-hydroxyvitamin D level below 30.0 ng/L.

Level of 25-hydroxyvitamin D were insufficient in 68% of the samples....Total testosterone was higher in men with normal levels of 25-hydroxyvitamin D than in men with lower levels...."subjects with hypovitaminosis D still had significantly lower total testosterone than those with normal total testosterone (P = .019)," Dr McLaughlin and her colleagues report. When levels of 25-hydroxyvitamin D were lower, body mass index was higher than when levels were normal (30.8 vs 29.12 kg/m²; P < .001), waist circumference was greater (41.3 vs 39.8 inches; P < .001), and lipid profiles were less favorable.

In previous studies, testosterone levels were shown to be lower in mice who had the vitamin D receptor genetically deleted, said Dr McLaughlin."This suggests that there is something about testosterone synthesis that needs vitamin D," she explained.

In a small German study of healthy overweight men with a low baseline level of 25-hydroxyvitamin D and testosterone levels at the lower end of the reference range, there was a significant increase in total testosterone levels after 12 months of vitamin D 3000 IU daily (Horm Metab Res. 2011;43:223-225)...the German study was primarily a weight-loss study, and weight loss in and of itself causes increases in testosterone."We see that in patients who undergo bariatric surgery to remove visceral fat," he explained. "Once the weight loss has taken place, their testosterone levels normalize independent of anything else."

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Another good reason to breastfeed. Exposure to pollutants like nitrogen dioxide and airborne particles can cause negative effects on motor and mental development in infants, but a new study says those effects are countered in babies who are breast-fed for at least 4 months by their mothers. Researchers in Spain began monitoring rural, pregnant women in 2006 and analyzed samples from 638 women and their infants at 15 months. They reported that babies who are breast-fed did not suffer from the potentially harmful developmental impact of PM2.5 (pollution particle matter) and NO2 (nitrogen dioxide). From Science Daily:

Breastfeeding protects against environmental pollution

Living in a city with a high level of vehicle traffic or close to a steel works means living with two intense sources of environmental pollution. However, a study conducted by the UPV/EHU researcher Aitana Lertxundi indicates that the harmful effect of PM2.5 pollution particle matter and nitrogen dioxide (NO2) disappears in breastfed babies during the first four months of life. According to the results of the research, breastfeeding plays a protective role in the presence of these two atmospheric pollutants.

Lertxundi's study focusses on the repercussions on motor and mental development during the first years of life caused by exposure to the PM2.5 and NO2 atmospheric pollutants .... "In the fetal phase the central nervous system is being formed and lacks sufficient detoxification mechanisms to eliminate the toxins that build up," pointed out Aitana Lertxundi.

The PM2.5 particles measure less than 2.5 micra, in other words, they are four times thinner that a single hair and are suspended in the air. As they are so small they can easily penetrate the body and as they weigh so little they can spread without any difficulty through the air and can move far away from the initial emission source. The composition of these neurotoxic particles depends on the emission sources in the area. The INMA Gipuzkoa area under study has a high presence of neurotoxic particle matter made up of lead, arsenic and manganese from industrial activity and traffic. In comparison with urban averages where the main source of pollution is traffic, the concentration is lower.

One result of the study is that the existence of an inverse relationship has been detected between exposure to pollution particle matter and the motor development of babies. In this respect, the researcher highlights the fact that "these indices display an alteration with respect to the average and, even if they are not worrying, they are significant in that they reveal the relationship existing between air quality and motor development." The analysis of the data also shows that neither the PM2.5 particle matter nor the NO2 exert a harmful effect on babies breastfed on mother's milk for at least four months.

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Finding out that so many of probiotics currently contain traces of gluten is of serious concern to people wishing to avoid gluten in food products, for example those with celiac disease. Too bad the researchers didn't publish the brands.From Science Daily:

Many probiotics are contaminated with traces of gluten

More than half of popular probiotics contain traces of gluten, according to an analysis. Tests on 22 top-selling probiotics revealed that 12 of them (or 55%) had detectable gluten. Gluten is a protein found in wheat, rye, and barley, and patients with celiac disease need to eliminate it from their diet or face pain, bowel symptoms, and an increased risk of cancer.

Probiotics are commonly taken by patients for their theoretical effect in promoting gut health, though evidence of benefits is limited to a few clinical situations. "Many patients with celiac disease take dietary supplements, and probiotics are particularly popular," said Dr. Samantha Nazareth, a gastroenterologist at CUMC and the first author of the study. "We have previously reported that celiac patients who use dietary supplements have more symptoms than non-users, so we decided to test the probiotics for gluten contamination," said Dr. Nazareth.

 Most of the probiotics that tested positive for gluten contained less than 20 parts per million of the protein, and would be considered gluten-free by Food and Drug Administration (FDA) standards. However, four of the brands (18% of the total) contained in excess of that amount.

More than half of the 22 probiotics were labeled gluten-free, but this had no bearing on whether or not traces of gluten were present. Two probiotics that did not meet FDA standards carried the label.It is uncertain whether these trace amounts of gluten could cause symptoms or otherwise harm patients with celiac disease. 

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Finding endocrine disrupting chemicals in 2 out of 10 baby teethers, which are supposedly safe products for babies, is disturbing. Unfortunately the study did not give the manufacturers names. There was even an 11th teether made of natural rubber that was found to leach compounds that were "cytotoxic"(toxic to living cells), but the manufacturer recalled the product before the study results were published. One of the teethers leaching parabens was made of EVA plastic filled with a cooling gel, and the researchers thought the parabens came from the gel used. Note that this study occurred in Europe where the regulations regarding endocrine disrupting chemicals are stricter than in the USA. The researchers themselves suggest that manufacturers should use "green chemistry" when manufacturing products - that is, design products without using problem ingredients right from the start. Problem solved. From Science Daily:

Endocrine disrupting chemicals in baby teethers

In laboratory tests, two out of ten teethers, plastic toys used to sooth babies' teething ache, release endocrine disrupting chemicals. One product contains parabens, which are normally used as preservatives in cosmetics, while the second contains six so-far unidentified endocrine disruptors. 

"The good news is that most of the teethers we analyzed did not contain any endocrine disrupting chemicals. However, the presence of parabens in one of the products is striking because these additives are normally not used in plastic toys," says Dr. Martin Wagner, of the Department Aquatic Ecotoxicology at the Goethe University. The substances detected -- methyl, ethyl and propyl parabens -- can act like natural oestrogen in the body and, in addition, inhibit the effects of androgens such as testosterone. The EU Commission recently banned two parabens in certain baby cosmetics, because of concerns over their health effects.

"Our study shows that plastic toys are a source of undesirable chemicals. Manufacturers, regulatory agencies and scientists should investigate the chemical exposure from plastic toys more thoroughly," Wagner concludes from the study. The additives have only limited benefits for the quality of the product, but can represent a potential health issue. This is especially true for babies and infants, whose development is orchestrated by a delicately balanced hormonal control and who are more susceptible to chemicals exposures than adults.

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Controversy exists over whether healthy people should take statins because of possible side effects. This is another study finding a very elevated risk of new onset diabetes, high risk of diabetes complications, and obesity in statin users. This finding was also significant because the statins were given to healthy people (with no heart disease, diabetes, or severe chronic disease). Risks of diabetes, diabetes complications, and obesity were dose related. Statin users were also paired with similar non-statin users and then followed - thus the only differences between the 2 groups was whether they used statins. The researchers themselves write that when considering risks of statins, people should try for lifestyle changes (lose weight, eat healthy, exercise, stop smoking) rather than just rely on popping a pill. From Medical Xpress:

Strong statin-diabetes link seen in large study of Tricare patients

In a database study of nearly 26,000 beneficiaries of Tricare, the military health system, those taking statin drugs to control their cholesterol were 87 percent more likely to develop diabetes.

The study, reported online April 28, 2015, in the Journal of General Internal Medicine, confirms past findings on the link between the widely prescribed drugs and diabetes risk. But it is among the first to show the connection in a relatively healthy group of people. The study included only people who at baseline were free of heart disease, diabetes, and other severe chronic disease."In our study, statin use was associated with a significantly higher risk of new-onset diabetes, even in a very healthy population," says lead author Dr. Ishak Mansi. 

In the study, statin use was also associated with a "very high risk of diabetes complications," says Mansi. "This was never shown before." Among 3,351 pairs of similar patients—part of the overall study group—those patients on statins were 250 percent more likely than their non-statin-using counterparts to develop diabetes with complications. Statin users were also 14 percent more likely to become overweight or obese after being on the drugs....The study also found that the higher the dose of any of the statins, the greater the risk of diabetes, diabetes complications, and obesity.

A key strength of Mansi's study was the use of a research method known as propensity score matching. Out of the total study population, the researchers chose 3,351 statin users and paired them with non-users who were very similar, at baseline, based on array of 42 health and demographic factors. The only substantial difference, from a research standpoint, was the use of statins. This helped the researchers isolate the effects of the drugs.

On a wider scale, looking at the overall comparison between the study's roughly 22,000 nonusers and 4,000 users, and statistically adjusting for certain factors, the researchers found a similar outcome: Users of statins were more than twice as likely to develop diabetes.The researchers examined patient records for the period between October 2003 and March 2012. About three-quarters of the statin prescriptions in Mansi's data were for simvastatin, sold as Zocor.

"I myself am a firm believer that these medications are very valuable for patients when there are clear and strict indications for them," he says. "But knowing the risks may motivate a patient to quit smoking, rather than swallow a tablet, or to lose weight and exercise. Ideally, it is better to make those lifestyle changes and avoid taking statins if possible."

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Published on 1 Comment on Obesity Markers Found In Urine

You can deceive yourself by calling yourself "big-boned" or "hefty", but your urine doesn't lie! Researchers found 29 biological markers in urine that are associated with body mass. These biological markers in urine are a "metabolic signature" of obesity. Note: Body mass index (BMI) is a measure of body fat based on height and weight that applies to adult men and women. From Medical Xpress:

Urine profiles provide clues to how obesity causes disease

Scientists have identified chemical markers in urine associated with body mass, providing insights into how obesity causes disease. Being overweight or obese is associated with higher risk of heart disease, stroke, diabetes and cancer, but the mechanisms connecting body fat and disease are not well understood.

The new study, led by Imperial College London, shows that obesity has a 'metabolic signature' detectable in urine samples, pointing to processes that could be targeted to mitigate its effects on health. 

Urine contains a variety of chemicals known as metabolites, from a vast range of biochemical processes in the body. Technologies that analyse the metabolic makeup of a sample can therefore offer huge amounts of information that reflects both a person's genetic makeup and lifestyle factors.

The Imperial researchers analysed urine samples from over 2,000 volunteers in the US and the UK. They found 29 different metabolic products whose levels correlated with the person's body mass index, and how they fit together in a complex network that links many different parts of the body.

Some of these metabolites are produced by bacteria that live in the gut, highlighting the potentially important role these organisms play in obesity. Altered patterns of energy-related metabolites produced in the muscles were also identified as being linked to obesity.

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Since so many people are taking Vitamin D supplements because of its supposed health benefits, the question becomes - how much is too much? For those desiring to take vitamin D supplements, what is a good maintenance dosage to take daily? That question has not been answered from the studies I've seen other than 1000 units per day is safe. However, sunlight is the best and safest source of vitamin D (even though that makes dermatologists nuts because of their concern with sunlight leading to skin cancer).From Science Daily:

Vitamin D toxicity rare in people who take supplements, researchers report

Over the last decade, numerous studies have shown that many Americans have low vitamin D levels and as a result, vitamin D supplement use has climbed in recent years. Vitamin D has been shown to boost bone health and it may play a role in preventing diabetes, cancer, cardiovascular disease and other illnesses. In light of the increased use of vitamin D supplements, Mayo Clinic researchers set out to learn more about the health of those with high vitamin D levels. They found that toxic levels are actually rare.

A vitamin D level greater than 50 nanograms per milliliter is considered high. Vitamin D levels are determined by a blood test called a serum 25-hydroxyvitamin D blood test. A normal level is 20-50 ng/mL, and deficiency is considered anything less than 20 ng/mL, according the Institute of Medicine (IOM).

The researchers analyzed data collected between 2002 and 2011 from patients in the Rochester Epidemiology Project...Of 20,308 measurements, 8 percent of the people who had their vitamin D measured had levels greater than 50 ng/mL, and less than 1 percent had levels over 100 ng/mL.

"We found that even in those with high levels of vitamin D over 50 ng/mL, there was not an increased risk of hypercalcemia, or elevated serum calcium, with increasing levels of vitamin D," says study co-author Thomas D. Thacher, M.D., a family medicine expert at Mayo Clinic. Hypercalcemia, or high blood calcium, can occur when there are very high levels of vitamin D in the blood. Too much calcium in the blood can cause weakness, lead to kidney stones, and interfere with the heart and brain, and even be life threatening.

The Mayo researchers also found that women over age 65 were at the highest risk of having vitamin D levels above 50 ng/mL. The result was not surprising because that's a group that often takes vitamin D supplements, Dr. Thacher says. Another notable outcome: The occurrence of high vitamin D levels over 50 ng/mL increased during the 10-year period of the study, from nine per 100,000 people at the start of the study up to 233 per 100,000 by the end.

Only one case over the 10-year study period was identified as true acute vitamin D toxicity; the person's vitamin D level was 364 ng/mL. The individual had been taking 50,000 international units (IU) of vitamin D supplements every day for more than three months, as well as calcium supplements. The IOM-recommended upper limit of vitamin D supplementation for people with low or deficient levels is 4,000 IU a day. 

Some natural sources of vitamin D include oily fish such as mackerel and salmon, fortified milk, and sunlight.

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This nice general summary of what scientists know about the microbial community within us was just published by a division of the NIH (National Institutes of Health). Very simple and basic. From the National Institute of General Medical Sciences (NIGMS):

Facts about our microbial menagerie

Trillions of microorganisms inhabit us -- inside and out. Scientists are surveying these microbial metropolises to learn more about their role in health. Microbiologists Darren Sledjeski of the National Institutes of Health (NIH) and Andrew Goodman of Yale University share a few details of what researchers have learned so far.

1. The majority of the microbes that inhabit us are bacteria. The rest of the microbial menagerie is fungi and viruses, including ones that infect the bacteria! Collectively, our resident microorganisms are referred to as the human microbiota, and their genomes are called the human microbiome.

2. Our bodies harbor more bacterial cells than human ones. Even so, the microbiota accounts for less than 3 percent of a person's body mass. That's because our cells are up to 10,000 times bigger in volume than bacterial cells.

3. Your collection of bacteria has more genes than you do. Scientists estimate that the genomes of gut bacteria contain 100-fold or more genes than our own genomes. For this reason, the human microbiome is sometimes called our second genome.

4. Most of our microbes are harmless, and some are helpful. For example, harmless microbes on the skin keep infectious microbes from occupying that space. Microbes in the colon break down lactose and other complex carbohydrates that our bodies can't naturally digest.

5. Different microbes occupy different parts of the body. Some skin bacteria prefer the oily nooks near the nose, while others like the dry terrain of the forearm. Bacteria don't all fare well in the same environment and have adapted to live in certain niches.

6. Each person's microbiota is unique. The demographics of microbiota differ among individuals. Diet is one reason. Also, while a type of microbe might be part of one person's normal microbial flora, it might not be part of another's, and could potentially make that person sick.

7. Host-microbial interactions are universal. Microbial communities may vary from person to person, but everyone's got them, including other creatures. For this reason, researchers can use model organisms to tease apart the complexities of host-microbial interactions and develop broad principles for understanding them. The mouse is the most widely used animal model for microbiome studies.

8. The role of microbiota in our health isn't entirely clear. While it's now well accepted that the microbial communities that inhabit us are actively involved in a range of conditions -- from asthma to obesity -- research studies have not yet pinpointed why or how. In other words, the results may suggest that the presence of a bacterial community is associated with a disease, but they don't show cause and effect.

9. Most of our microbes have not been grown in the lab. Microbes require a certain mix of nutrients and other microbes to survive, making it challenging to replicate their natural environments in a petri dish. New culturing techniques are enabling scientists to study previously uncultivated microbes.

10. The impact of probiotic and prebiotic products isn't clear. Fundamental knowledge gaps remain regarding how these products may work and what effects they might have on host-microbial interactions. A new NIH effort to stimulate research in this area is under way.

11. There's even more we don't know! Additional areas of research include studying the functions of microbial genes and the effects of gut microbes on medicines. The more we learn from these and other studies, the more we'll understand how our normal microbiota interacts with us and how to apply that knowledge to promote our health.

Lactobacilli. Credit: Wikipedia.

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Another study finding negative effects of air pollution - this time high levels of traffic-related air pollution is linked to slower cognitive development among 7 to 10 year old children in Barcelona, Spain. From Science Daily:

Air pollution linked to slower cognitive development in children

Attendance at schools exposed to high levels of traffic-related air pollution is linked to slower cognitive development among 7- to 10-year-old children in Barcelona, according to a new study.

The researchers measured three cognitive outcomes (working memory, superior working memory, and attentiveness) every 3 months over a 12-month period in 2715 primary school children attending 39 schools. By comparing the development of these cognitive outcomes in the children attending schools where exposure to air pollution was high to those children attending a school with a similar socio-economic index where exposure to pollution was low, they found that the increase in cognitive development over time among children attending highly polluted schools was less than among children attending paired lowly polluted schools, even after adjusting for additional factors that affect cognitive development.

Thus, for example, there was an 11.5% 12-month increase in working memory at the lowly polluted schools but only a 7.4% 12-month increase in working memory at the highly polluted schools. These results were confirmed using direct measurements of traffic related pollutants at schools.

The findings suggest that the developing brain may be vulnerable to traffic-related air pollution well into middle childhood, a conclusion that has implications for the design of air pollution regulations and for the location of new schools. While the authors controlled for socioeconomic factors, the accuracy of these findings may be limited by residual confounding, that is, the children attending schools where traffic-related pollution is high might have shared other unknown characteristics that affected their cognitive development.