Tuesday, September 26, 2017

How Diabetes Drives Atherosclerosis


March 17, 2008
Source:
University of Rochester Medical Center
Summary:
Researchers have discovered how diabetes, by driving inflammation and slowing blood flow, dramatically accelerates atherosclerosis. Experts once believed that atherosclerosis, or hardening of the arteries, developed when too much cholesterol clogged arteries with fatty deposits called plaques. When blood vessels became completely blocked, heart attacks and strokes occurred. Today most agree that the reaction of the body's immune system to fatty build-up, more than the build-up itself, creates heart attack risk.

Researchers have discovered how diabetes, by driving inflammation and slowing blood flow, dramatically accelerates atherosclerosis, according to research to be published in the March 14 edition of the journal Circulation Research.
Experts once believed that atherosclerosis, or hardening of the arteries, developed when too much cholesterol clogged arteries with fatty deposits called plaques. When blood vessels became completely blocked, heart attacks and strokes occurred. Today most agree that the reaction of the body's immune system to fatty build-up, more than the build-up itself, creates heart attack risk. Immune cells traveling with the blood mistake fatty deposits for intruders, akin to bacteria, home in on them, and attack. This causes inflammation that makes plaques more likely to swell, rupture and cut off blood flow.
Making matters worse, nearly 21 million Americans have diabetes, a disease where patients' cells cannot efficiently take in dietary sugar, causing it to build up in the blood. In part because diabetes increases atherosclerosis-related inflammation, diabetic patients are twice as likely to have a heart attack or stroke.
Past work has shown that high blood sugar has two effects on cells lining blood vessels as part of atheroslerosis. First, it increases the production of free radicals, highly reactive molecules that tear about sensitive cell components like DNA, causing premature cell death (apoptosis). This process also reduces the availability of nitric oxide (NO), which would otherwise enable blood vessels to relax and blood flow to increase.
In contrast to diabetes, exercise and good diet bring about faster blood flow through blood vessels. The force created by fast, steady blood flow as it drags along blood vessel walls has been shown by recent studies to protect arteries from atherosclerosis. Physical force has emerged recently as a key player in bodily function, capable of kicking off biochemical processes (e.g. weightlifting thickens bone).
"Inflammation in blood vessels is one of the main drivers of atherosclerosis, and diabetes makes it much worse," said Jun-ichi Abe, M.D., Ph.D., associate professor with the Aab Cardiovascular Research Center at the University of Rochester Medical Center, and a study author. "Our study argues that a pathway surrounding a key signaling enzyme both protects the heart in normal cases, and is sabotaged by the chemicals produced in diabetes. We believe we have found a new therapeutic target for the treatment of diabetes-related damage to blood vessels."

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Sunday, September 24, 2017

Low Brain Cholesterol—Separating Fact from Fiction



Where do you find the highest concentration of cholesterol in your whole body? In your BRAIN. The brain is cholesterol-rich on purpose—because it needs large amounts of cholesterol to function properly. So, what does that mean for the growing number of people choosing naturally cholesterol-free plant-based diets? And what about the 15 million Americans who take statin medications like Lipitor to lower their cholesterol levels? People who are trying to lower their cholesterol levels are worried about heart health. But how does lowering cholesterol affect mental health?
What is cholesterol?
Poor cholesterol—so misunderstood. Cholesterol is a waxy substance naturally embedded in our membranes, the flexible packaging surrounding every cell in our bodies. Cholesterol contributes structural firmness to membranes and keeps them from falling apart. Membranes are not simply protective cell wrappers; they are dynamic, highly intelligent structures that participate in cellular signaling and the transport of substances into and out of cells. Cholesterol is also an essential ingredient in vitamin D and many other hormones in the body, including estrogen and testosterone. All animal foods (meat, seafood, poultry, dairy, and eggs) contain cholesterol because all animal cells need cholesterol. 

Why does the brain need cholesterol?

Although the brain represents only 2% of total body weight, it contains 20% of the body’s cholesterol. What is all that cholesterol doing up there? Synapses— the magical areas where communication between brain cells takes place—are lined by cholesterol-rich membranes responsible for passing neurotransmitters like serotonin, GABA, and dopamine back and forth. Myelin, the white matter that insulates brain circuits, is made from tightly-wound membranes containing 75% of the brain’s cholesterol. Cholesterol also helps guide developing nerve endings to their destinations on “lipid rafts”. If the brain is too low in cholesterol, its membranes, synapses, myelin and lipid rafts can’t form or function properly, bringing all brain activity—including mood regulation, learning, and memory— to a screeching halt.

Do people who take statin drugs need to worry about low brain cholesterol? 

YES. “Statins” are drugs designed to lower your level of LDL cholesterol—the so-called “bad cholesterol.” They work by turning down the activity of HMG-CoA reductase, the enzyme our cells use to build new cholesterol molecules. Unfortunately, statins do cross the blood-brain barrier and enter brain cells, where they reduce the brain’s natural ability to make the beautiful cholesterol molecules the brain needs to do its important work.
We used to think that only certain statin drugs could cross into the brain, but it turns out that they ALL do; it’s just that some reach higher levels inside the brain than others. But don’t let that lull you into a sense of false security—even Pravastatin (Pravachol), which has the hardest time making the journey, penetrates the brain enough to interfere with its cholesterol factory. 
There haven’t been many human experiments testing the effects of statins on brain function, but the few that have been done suggest there is a real risk of cognitiveproblems in some people:
“RCTs [randomized controlled trials] on effect of statins and cognitive function have shown debatable and controversial results with three RCTs reporting poorer performance scores in a minority of cognitive tests among statin users. Hence, we conclude that there is a need for more randomized control trials and until then benefits of statins must be weighed against the risks of cognitive decline on an individual basis.” [Chatterjee S et al 2015 Curr Cardiol Rep 17:4]
All statin manufacturer package inserts include the same warning:
“There have been rare postmarketing reports of cognitive impairment (e.g., memory loss, forgetfulness, amnesia, memory impairment, confusion) associated with statin use. These cognitive issues have been reported for all statins. The reports are generally nonserious, and reversible upon statin discontinuation, with variable times to symptom onset (1 day to years) and symptom resolution (median of 3 weeks).” 
Nonserious? Seriously? I don’t know about you, but I wouldn’t want any of those side effects. They say they are rare, but “post-marketing” reports tend to be rare, because most people don’t report side effects directly to the manufacturer. If you feel fuzzy-headed on a statin, trust your experience over the fine print. Stop the statin and see for yourself if the fog lifts. 

Statins and Heart Disease

Stop the statin?! What about high cholesterol and heart disease? Won’t millions of arteries across the country slam shut?
Statins are a bad idea —not just because they can gum up your brain, slow your hormone production, reduce your coenzyme Q10 levels, cause muscle pain, and put you at risk for other potential side effects, but also because they may not even reduce your risk for heart attacks. Prominent cardiologist Dr. Aseem Malhotra agrees: heart disease is NOT about cholesterol or saturated fat.
Heart disease is about insulin resistance (aka pre-diabetes) and inflammation within your blood vessels. Diets high in refined carbohydrates (like sugar, flour, cereals and fruit juice) can lead to abnormally high insulin levels. It just so happens that insulin boosts the activity of your cholesterol-building enzyme, HMG-CoA-reductase—the very same enzyme that statin drugs suppress! [Nelson DL, Cox MM. Lehninger Principles of Biochemistry. 5th ed. New York, NY: W.H. Freeman; 2008:842.]

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Monday, September 18, 2017

Surgical Castration Instead of Drugs in Prostate Cancer

For some men with metastatic prostate cancer, surgical castration to remove the testicles (orchiectomy) could be a better option than "chemical castration" achieved by long-term use of prostate gonadotropin-releasing hormone (GnRH) agonist products, as it may carry less risk for adverse events, suggests a new study published online December 23 in JAMA Oncology.
"The paradigms of treatment for advanced prostate cancer are ever changing, but there remains a group of men who require permanent castration. For those men, orchiectomy is a reasonable alternative that is associated, according to our study, with lower risks of fractures, peripheral arterial disease, and cardiac-related complications than GnRH agonists," commented lead author Quoc-Dien Trinh, MD, from Harvard Medical School in Boston, Massachusetts.
"Unfortunately, for a multitude of reasons, most of which are unjustified, urologists and medical oncologists no longer offer the option of orchiectomy," he continued. "This is in spite of guidelines continuing to recommend orchiectomy as a first-line treatment for men presenting with metastatic prostate cancer."

For the last 50 years, androgen-deprivation therapy has been the cornerstone of treatment of metastatic prostate cancer, the authors write.
However, achieving androgen deprivation by bilateral orchiectomy has basically been eliminated from clinical practice, mainly because of aesthetic and psychological issues, but also because medical therapy is reversible and easy to administer, the authors write.
The current standard of care is long-term use of GnRH agonist products such as goserelin (Zoladex, AstraZeneca) and leuprolide (Lupron, AbbVie).
However, there is mounting evidence that androgen-deprivation therapy is linked to significant adverse effects, such as cardiovascular events, diabetes, acute kidney injury, and bone loss, the authors write. The US Food and Drug Administration requires that GnRH agonist product labeling include a warning about the increased risk for diabetes and cardiovascular disease.
Past research looking at adverse cardiac events associated with GnRH agonist products has suggested there is a lower cardiac risk in patients with orchiectomies. That led to the hypothesis that cardiac adverse effects may be related to GnRH agonist products, rather than androgen deprivation per se.
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Saturday, September 9, 2017

Muscle Growth and Estrogen

Estrogen is often called a “female hormone,” which is a misnomer, as this steroid hormone is also produced in the male body. It’s also true that women produce far greater amounts of estrogen than men, just as men produce about 10 times more testosterone than women.
Men’s greater testosterone levels are often cited as the reason that they are able to build more muscle than women. Recent studies, however, show that despite the negligible amounts of testosterone they produce while weight training, women are able to make similar muscle gains to men’s. That relates more to the fact that anabolic hormones produced during exercise don’t have as great an effect on muscle growth as was previously realized. Think about that the next time you read an article about the best ways to boost anabolic hormones during training.
If men’s bodies produce estrogen, what is the purpose? After all, nature is not known to be profligate in its actions; everything it does, it does for a reason. Although the precise functions of estrogen in men aren’t entirely clear, it appears to play a role in the maturation and development of sperm, which means that estrogen may effect male fertility.
Estrogen is vital to bone development in women, and a lack of it in older women often results in osteoporosis, a bone-thinning disease. Some scientists suggest that estrogen may play a similar role in men. Men deficient in testosterone are also subject to osteoporosis, although it’s not as common in men as in women, and when it does occur, it usually strikes in the spine.
Men are often advised not to take supplements or drugs that lower estrogen for extended times because of possible adverse affects on the cardiovascular system. That’s based on the established cardiovascular protection offered by estrogen to women. Younger women rarely suffer from heart attacks or strokes, and the reason is attributed to their higher estrogen levels. Estrogen offers cardiovascular protection in several ways. For one thing, it aides the synthesis and release of nitric oxide.

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