Friday, April 20, 2018

Time to Ditch ACE Inhibitors for CVD?

There is “little, if any, clinical reason” to use angiotensin-converting enzyme (ACE) inhibitors for the treatment of hypertension or other cardiovascular indications because angiotensin receptor blockers (ARBs) are just as effective with fewer side effects, a new review concludes.

The review, published in the Journal of the American College of Cardiology on April 3, was led by Franz Messerli, MD, University Hospital, Bern Switzerland.

Messerli and colleagues reviewed data from 119 randomized clinical trials of ACE inhibitors and ARBs in more than half a million patients and found no difference in efficacy between the two drug classes with regard to the surrogate endpoint of blood pressure and the outcomes of all-cause mortality, cardiovascular mortality, myocardial infarction, heart failure, stroke, and end-stage renal disease. But ACE inhibitors have a higher incidence of adverse reaction – namely cough and very low risks of angioedema and fatalities – that are more prevalent in dark-skinned people, they write.

Despite this, most guidelines for the management of patients with cardiovascular disease recommend ACE inhibitors as first-choice therapy, whereas ARBs are merely considered an alternative for ACE inhibitor-intolerant patients, Messerli and colleagues point out.

My Take:
The rest of the article is rebuttal from various cardiologists on the pros and cons of using ARBs in lieu of ACE. The best quote – “And the side effect of angioedema, although rare, can be fatal, and if ACE inhibitors are proposed as part of the polypill then millions will be exposed and fatalities will occur.”

Wednesday, April 18, 2018

Wisdom Wednesday: Blood Test Detects Alzheimer’s Before Symptoms Appear


One of the major issues that hamper Alzheimer’s research is that the disease is always caught at a relatively late stage. This is because symptoms develop slowly over several years; they become obvious long after the condition has made changes in the brain.

The only reliable methods of diagnosis are positron emission tomography (PET) scan and cerebrospinal fluid (CSF) analysis collected by lumbar puncture.

One of the hallmarks of Alzheimer’s disease is an abnormal buildup of amyloid-beta plaques in the brain. Amyloid-beta is present in the healthy brain, but, in individuals with Alzheimer’s the protein is folded incorrectly and accumulates. Amyloid-beta plaque clusters can begin developing 15-20 years before symptoms of Alzheimer’s appear.

This unhealthy protein is the basis of a new blood test. In a study published in the journal EMBO Molecular Medicine, researchers led by Klaus Gerwert, describe their groundbreaking work.

The new blood test uses immune-infrared sensor technology. Based on an antibody, the sensor extracts all amyloid-beta from the blood sample. The two versions of amyloid-beta absorb infrared light at different frequencies allowing he researchers to measure the relative levels of healthy and unhealthy protein.

In the initial phase of the study individuals who showed subtle, early symptoms of Alzheimer’s, the test detected changes in levels of amyloid-beta that correlated with abnormal deposits visualized using brain scans.

In the next phase, they assessed blood samples from 65 individuals who later went on to develop Alzheimer’s and compared them with 809 individuals who did not develop the disease. On average, the blood test could detect Alzheimer’s in individuals 8 years before clinical symptoms became apparent.

Monday, April 16, 2018

The Bittersweet Truth

Taste receptor cells are not confined to the oral cavity. The gut and pancreas are inundated with taste receptor cells. Taste cells in the gut and pancreas do not convey the sensation of taste to the brain. Instead, they are responsible for sensing nutrients and maintaining the balance of hormones essential in metabolic processes. Activation of these receptors by their respective sweet or bitter substances triggers the release of hormones that regulate appetite and satiety and help maintain appropriate glucose levels in the blood stream. This observation has drawn a plausible link between dysfunction of taste receptor cells and the emergence of diseases such as obesity and diabetes.

Sweet taste receptors in the enteroendocrine cells (cells that secrete hormones) of the gut and pancreas are suggested to play an important role in nutrient sensing and sugar absorption, both processes necessary for energy and maintaining a normal metabolism. When sweet taste receptors sense sugars, they elicit the release of gut hormones. One such hormone, glucagon-like peptide 1 (GLP-1), is responsible for facilitating the absorption of glucose into the bloodstream, enhancing insulin secretion in the pancreas and regulating appetite. Disruptions in any of these physiological processes can result in the development of type II diabetes. In a study aiming at quantifying the levels of sweet taste receptors in the upper gut of healthy and diabetic individuals, researchers observed that the levels of sweet taste receptors were diminished in diabetic type II subjects with elevated blood glucose concentrations. This observation was consistent with previous results showing that type II diabetes patients secreted low levels of GLP-1 in response to a meal in comparison to healthy individuals.

Sweet taste receptors in the gut and pancreas also “taste” artificial sweeteners, also known as non-nutritive sweeteners (NNS). Several research groups found that exposure of mouse cells to sucralose, the sweetener in Splenda, caused the release of GLP-1.

Friday, April 13, 2018

Alzheimer’s: Scientists find the cause of evening agitation

A new study has uncovered a biological clock circuit that may explain why people with Alzheimer’s disease or other forms of dementia can become more agitated or aggressive in the early evening.

Sundowning is a condition that is typically seen in people with Alzheimer’s, when behavior becomes restless, agitated, and aggressive, accompanied by confusion. Its name is derived from the fact that it usually begins or gets worse in the late afternoon or early evening.

Biological clocks are specific groups of proteins that communicate with cells in nearly every organ and most tissue in the body. They respond to changes in light and dark in the environment and give rise to the circadian rhythms – that is physical, behavioral, and mental changes that “follow a daily cycle.”

Scientists have discovered that the genes that make and control the various components of biological clocks are largely similar in humans, mice, fruit flies, fungi and many other organisms. While biological clocks are found nearly everywhere in the body, they are all synchronized by a “master clock’ in the brain.

In humans, mice, and other vertebrates, the master clock is located in the suprachiasmatic nucleus, which is a cluster of neurons inside the hypothalamus region of the brain. The cluster contains around 20,000 cells and receives signals directly from the eyes.

For their study, Prof. Saper and his colleagues measured the frequency and intensity of interactions between male mice as “resident mice” defended their territory against “intruder mice” that were introduced into their cages at different times of the day. “The mice,” explains Prof. Saper, “were more likely to be aggressive in the early evening around lights out, and least aggressive in the early morning, around lights on.” “It looks like aggressiveness,” he continues, “build up in mice during the lights on period, and reaches a peak around the end of the light period.”

In another set of experiments, the researchers manipulated the mice’s master biological clock by tweaking genes in the neurons that regulate it. They found that when they stopped the master clock neurons from being able to make a specific chemical messenger, or neurotransmitter, the mice lost their circadian pattern of aggression. Aggressiveness remained high all the time, showing no highs and lows.

Wednesday, April 11, 2018

Wisdom Wednesday: Oral Vitamin B12 Versus Intramuscular Vitamin B12


Vitamin B12 deficiency is common, and the incidence increases with age. Most people with vitamin B12 deficiency are treated in primary care with intramuscular (IM) vitamin B12. Doctors may not be prescribing oral vitamin B12 formulations because they may be unaware of this option or have concerns regarding its effectiveness.

The goal of the review was to assess the effects of oral vitamin B12 versus intramuscular vitamin B12 for vitamin B12 deficiency.

The primary outcomes of data collection and analysis were serum vitamin B12 levels, clinical signs and symptoms of vitamin B12 deficiency, and adverse events. Secondary outcomes were health-related quality of life, acceptability to patients, hemoglobin and mean corpuscular volume, total homocysteine and serum methylmaloic acid levels.

Only three RCTs met our inclusion criteria. The trials randomized 153 participants (74 participants to oral vitamin B12 and 79 participants to IM vitamin B12). Treatment duration and follow-up ranged between three and four months. The mean age of participants ranged from 38.6 to 72 years. The treatment frequency and daily dose of vitamin B12 in the oral and IM groups varied among trials. The overall quality of evidence for this outcome was low due to serious imprecision (low number of trials and participants). In two trials employing 1000 ug/day oral vitamin B12, there was no clinically relevant difference in vitamin B12 levels when compared with IM vitamin B12. Orally taken vitamin B12 showed lower treatment associated costs than IM vitamin B12.

Low quality evidence shows oral and IM vitamin B12 having similar effects in terms of normalizing serum vitamin B12 levels. Further trials should conduct better randomization and blinding procedures, recruit more participants, and provide adequate reporting.

Monday, April 9, 2018

Clinically Useless

Patients with uncomplicated cellulitis frequently undergo blood culture and imaging, despite recommendations against routine use of such testing, finds a retrospective study in JAMA Internal Medicine. And the economic toll is significant.

Researchers examined the medical records of 183 patients seen at one emergency department with presumed uncomplicated cellulitis who were subsequently admitted. One third had blood cultures (with growth detected in 1 patient), but culture was deemed appropriate according to clinical guidelines in just 10% of the overall cohort. Additionally, nearly 70% underwent imaging (e.g., ultrasound, radiograph), and none of these tests were considered appropriate.

The researchers estimate that the national cost of “these largely clinically useless diagnostic studies” exceeds $225 million annually. They note that guidelines from the Infection Diseases Society of American recommend against imaging unless patients also have febrile neutropenia, and against culture unless patients are severely immunocompromised, show systemic toxic effects, or have had an animal bite.

My Take:
This is why we have the most expensive health care system in the world that ranks among the worst of all industrialized nations. The “standard of care” seemingly is only applied by physicians when it suits their purpose. Unfortunately, too often the goal is money.

Friday, April 6, 2018

Gut Microbiota Influencing Obesity

Polyphenols may generate numerous health benefits by modulating the gut microbiota (GM). Phytochemicals that can influence GM have recently been studied as adjuvants to support healthy weight and inflammatory response. These phytochemicals include polyphenols and their derivatives, carotenoids, and thiosulfates, which were “further sub-classified into four main groups: flavonoids (including eight subgroups), phenolic acids (such as curcumin), stilbenoids (such as resveratrol), and lignans.”

“An imbalance of GM, or dysbiosis, can be the cause of, or at least lead to the progression of several pathologies such as infectious diseases, gastrointestinal cancers, cardiovascular disease, inflammatory bowel disease, and even obesity and diabetes.” Of the phytochemicals ingested, 90-95% “reach the colon in high concentrations, where they are degraded by the microbial enzymes prior to absorption.

Joining the ranks of prebiotics and probiotics, polyphenols are now attracting interest in the media and the research community as potential therapeutic agents in supporting health weight management. Proposed mechanisms of actions include “inhibition of the differentiation of adipocytes, increased fatty acid oxidation, decreased fatty acid synthesis, increased thermogenesis, the facilitation of energy metabolism and weight management, and the inhibition of digestive enzymes.

As promising as this is, more research is required to determine [the] role of micronutrients and phytochemicals as therapeutic agents in modulating the GM, and, therefore, influencing weight management and the inflammatory response.

My Take:
If you read the current (and all past editions) Guyton’s Physiology it states that the “role of the colon is to reabsorb water to create a formed stool.” We now understand that colon has many roles, the least of which is to create a formed stool.

Wednesday, April 4, 2018

Wisdom Wednesday: Vitamin D Linked to Metabolic Syndrome in Postmenopausal Women


Postmenopausal women with vitamin D deficiency have greater risk for metabolic syndrome than those with sufficient levels, data from a cross-sectional cohort study suggest. Levels of 25-hydroxyvitamin-D below 20 ng/mL were also linked to a greater likelihood of high triglycerides and low high-density lipoprotein (HDL) cholesterol.

“These results suggest that the maintenance of adequate serum levels of 25(OH)D in postmenopausal women may reduce the risk of developing [metabolic syndrome], a condition that is known to be related to cardiovascular events and mortality in this group,” write Eneida Boteon Schmitt, MD, from Sao Paulo State University’s Botucatu Medical School in Brazil, and colleagues.

The study, published in the January 2018 issue of Maturitas, included 463 women, 45 to 75 years old, who had not menstruated for at least a year, were not taking vitamin D supplements, and had a diagnosis of cardiovascular disease. The researchers measured their total cholesterol, HDL levels, low-density lipoprotein (LDL) levels, triglycerides, glucose, insulin, and 25(OH)D levels.

Vitamin D deficiency was defined as serum 25(OH)D levels below 20ng/mL, whereas levels between 20 and 29 ng/mL were insufficient. Levels of at least 30 ng/mL were considered sufficient. Diagnosis of metabolic syndrome required presence of at least three of five criteria: a waist circumference greater that 88 cm, triglycerides at least 150mg/dL, HDL levels below 50 mg/dL, blood pressure at least 130/85, and glucose at least 100 mg/dL.

Just under a third (32.0%) of the women had sufficient vitamin D levels, and a similar proportion (32.6%) had insufficient levels. The remaining 35.4% were deficient. More than half (57.8%) of the women without sufficient vitamin D (below 30 ng/mL) had metabolic syndrome compared with 39.8% of the women with sufficient vitamin D levels.

Monday, April 2, 2018

Can Beets Tackle Alzheimer’s at Its Root?

Alzheimer’s disease is characterized by beta-amyloid plaques in the brain that disrupt the normal functioning of neurons. Could a common vegetal pigment provide the fix?

Researchers from the University of South Florida in Tampa have experimented with a compound called betanin, which is the pigment that give beets their dark red color. Li-Lune Ming, Darrell Cole Cerrato, and their colleagues explain that this vegetal pigment interacts with amyloid beta, preventing some of the processes that may have harmful effects on the brain. The results of the team’s research were presented this week at the 255th National Meeting & Exposition of the American Chemical Society, held in New Orleans, LA.

A study published last year in The Journals of Gerontology Series A showed that drinking beetroot juice before aerobic exercise made the aging brain look younger by increasing blood flow to the brain and regulating the circulation of oxygen.

Intrigued by this and similar research, Ming and team decided to see whether betanin, commonly found in these root vegetables, could be used to prevent amyloid beta from forming into clusters that impacted communication between brain cells.

Studies show that the aggregation of amyloid beta into harmful clusters is often dependent on their interaction with metal molecules – especially those of zinc and copper – in the brain. When such clusters do form, the researchers of the new study explain, amyloid beta facilitates brain inflammation and the oxidation of neurons, which results in irreparable damage to these brain cells.

They conducted a series of laboratory experiments in which they monitored the activity of amyloid beta in different contexts using 3, 5-Di-tert-butylcatechol (DTBC), a compound that allows researchers to observe the process of oxidation. By employing ultraviolet-visible spectrophotometry, the researchers saw that amyloid beta on its own did not produce much oxidative damage – but when it bound to copper molecules, the oxidation was considerable.