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Yearly Archives: 2013

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A growing number of studies show increased calcium to be dangerous

I just realized that February is American Heart Disease Awareness Month. My wife pointed out that this is also International Typewriter Appreciation Month, whatever that means. When was the last time that you used a typewriter? Therefore, I thought that my last article for the month of February should focus on this most prevalent disease and the dangers of calcium in increasing the risk of heart attacks and all-cause mortality.

I wrote about a very similar topic on April 26, 2011. First, let me summarize what we knew then. At that time, a study called the Women’s Health Initiative showed that calcium supplements may cause a 20 percent rise in the risk of heart attack (BMJ. 2011 April 19;342:d2040). There were 17,000 women involved in this study with calcium. The participants who saw this modest rise in risk were taking 1000 mg of calcium supplementation. In the same paper, there was also a meta-analysis (group of three studies) that showed increases of 20 percent in both heart attacks and strokes with calcium. It did not matter whether participants were taking vitamin D or not. At the time, I hedged my bets by saying it was only one paper. The results were intriguing, though — the risk of a heart attack surpassed the benefits of reducing fracture.

Recently, several large studies reinforced the negative effects of calcium as related to the heart, and the impact seems to be even greater. Let’s examine these studies and their implications in more detail.

Calcium’s impact on women

In the Swedish Mammography Cohort, published in the same medical journal as the aforementioned study, the results showed an almost 50 percent increased risk of cardiovascular disease deaths in women who consumed more than 1400 mg of calcium from their diet, which included calcium supplements, compared to those who consumed 600 to 1000 mg (BMJ. 2013 Feb. 13;346:f228). Cardiovascular disease risk in this study included heart disease and stroke combined. The participants who consumed less than 600 mg of calcium also had an increase in mortality, but not nearly as significant as the high calcium intake group.

When you break down the percentages, the data are even more interesting. In this study, heart disease deaths increased by 114 percent. However, unlike the previous study, there was no significant increase in stroke deaths.

All-cause mortality, which means from any source, not just cardiovascular, was increased by 40 percent. Also, those women in the high calcium group had a two-and-a-half times greater risk of all-cause death when they were taking calcium supplements, while those in the same group who were not taking supplements had a much less significant (17 percent) increased risk.

Not to worry. As the authors point out, those who consume calcium without supplements are most likely to be in the ideal range. This was a large observational prospective (forward-looking) study involving over 60,000 women. The duration of the study was 19 years. However, a weakness of the study is that the overall event rate was small. The authors’ conclusion was that women should avoid calcium supplementation and get their calcium from dietary sources.

Calcium’s impact on men

Not to be left out, men also seem to be negatively affected by high calcium. The National Institutes of Health-AARP Diet and Health Study, published a week earlier than the women’s study mentioned above, showed that there was a 20 percent increased risk of cardiovascular disease death in those men who took at least 1000 mg of calcium on a daily basis compared to those who did not (JAMA Intern Med. Online Feb. 4). Again, the predominant effect was seen with death from heart disease. This was a prospective study, involving 388,000 men and women who were followed for over 12 years.

To make the data slightly more obtuse, this effect was only seen in men, not in the women involved in the study. The authors cannot explain why there was this difference in gender. However, when the data was analyzed further, and multivitamins were eliminated from the equation as a contributing source of calcium, those men taking calcium supplements of at least 1000 mg were even more likely to suffer heart disease deaths, with a 37 percent increased risk.

In my own practice, having seen several hundred patients in the last few years, it seems none of them have been deficient in calcium. Yet when many patients come for an initial visit, they are taking varying amounts of calcium supplements. One of the first things I usually do is either reduce or discontinue the dose. I then follow up with a laboratory test to make sure they are not deficient after changing their supplements.

I also educate them about foods that are good sources of calcium and explain why. Believe it or not, we absorb calcium best from plant-based sources in our diet, such as kale, almonds, tofu and unhulled sesame seeds. In an article entitled, “Do calcium supplements increase cardiovascular mortality?“ published on Feb. 21, the author, after reviewing much of the pertinent data, suggests that calcium-rich foods are the wisest and safest of choices, rather than supplementation (www.medscape.com).

Finally, in the EPIC trial, there was a decrease in the risk of a heart attack from dietary calcium (Heart. 2012; 98(12):920-925). Unfortunately, there was no effect, beneficial or not, on the number of deaths from all-cause mortality or cardiovascular disease. However, there was a noticeable 139 percent increased risk of heart attacks in calcium supplement users.

Therefore, the best way to avoid this conundrum of making sure your bones are strong and getting enough calcium, while not increasing your risk of mortality is to do several things. Make sure your vitamin D levels are sufficient, for vitamin D helps with the absorption of calcium into the bones. Most people are deficient or insufficient (a milder form) in vitamin D, so if you want to take a supplement, start here. The other is to have a well-balanced diet that includes calcium-rich foods, ensuring you are in the optimal range of daily intake and getting very little or no calcium from supplements. Lastly, don’t begin using calcium supplements before consulting with your physician.

 

Dr. Dunaief is a speaker, author and local lifestyle medicine physician focusing on the integration of medicine, nutrition, fitness and stress management. For further information, go to the website www.medicalcompassmd.com and/or consult your personal physician.

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Finding a contrast agent that a surgeon could use to help delineate cancer cells from healthy ones

Jonathan Liu wants to see inside people’s brains. Specifically, he is working on a way he hopes will eventually give neurosurgeons a clearer look at the difference between malignant cells they want to remove in a specific type of tumor and healthy cells they’d rather not touch.

Taking out too many cells can damage the health of a patient, while not removing enough can give the tumor a chance to grow.

An assistant professor in biomedical engineering at Stony Brook University, Liu has tapped into his background in engineering to create microscopes that, in connection with a chemical called a contrast agent that lights up cancer cells, surgeons may one day use to see the edges of a tumor.

A doctor would “spray the contrast agent on at the final stages of surgery,” he explained. “It’s a way to check if there are any residual tumor cells.”

At this point, Liu and his graduate students, Danni Wang, Steven Leigh and Ye Chen, in conjunction with Stanford University, where Liu started this work as a postdoctoral student, have developed a system in animal models of medulloblastoma, a type of brain cancer, that makes the tumor glow.

In those animal models, medulloblastoma cells have a higher than normal amount of protein on their surface called Vascular Endothelial Growth Factor Receptor 1 (or VEGFR-1). Liu and his colleagues looked for a contrast agent that would stick to this protein and make it easy to find for surgeons.

“This is a specific contrast agent that we believe is labeling the tumor cells very accurately,” Liu said. “Normal cells would not overexpress this particular protein.”

The transition from these animal models of medulloblastoma to human forms will likely involve considerable study. Cancers can be highly variable and Liu explained that he wouldn’t expect all medulloblastomas to express VEGFR-1.

While the contrast agent and microscope could be years away from use in an operating room, the choice of a topical chemical, rather than a dye injected into a patient, may expedite the review process through the Food and Drug Administration.

Using a dye means the overall dosage could be lower, which would limit the introduction of the dye into the patient’s circulation.

Surgery has not yet reached the point where doctors can choose single cells to remove, Liu offered. Many brain tumor margins are diffuse and the cells can infiltrate and migrate through the brain, he explained. The goal, however, is to give the surgeon better guidelines.

A patient typically goes through chemotherapy to handle the remaining tumor. When surgeons remove more of the tumor, the postoperative therapies are generally also more effective, he asserted.

While the contrast agent the Stony Brook scientist used is innovative, the strengths of the design come from building the three-dimensional microscopes.

Liu designed a tabletop system for the recent results that were published in Translational Oncology. He is also creating a miniature handheld version that would be considerably more compact, in the form of a pen-like device.

As either a tabletop version or a handheld type, the microscope is “highly customized,” he related. “There’s nothing there that you can buy and get off the shelf.”

At Stanford, Liu built a similar microscope for the gastrointestinal tract. At Stony Brook, he has a new grant to develop a microscope to help with the early detection of oral cancers.

Receiving approval from regulators to use the newest microscope designs in the brain will require careful steps to ensure the instrument remains sterilized.

“You have to be very stringent,” Liu assured. He may surround the microscope in a plastic sheath, as medical researchers have done with similar devices.

Liu lives in Port Jefferson with his wife, Evie, a violin teacher who works at the Stony Brook School and gives lessons from home. They are both of Chinese descent and grew up in Hawaii.

Liu is an amateur surfer and enjoys going to the South Shore when a storm along the coast kicks up larger waves.

If he weren’t a scientist, Liu said he might consider a career as a doctor. He appreciates a physician’s opportunity to have a positive impact on their patients’ lives.

Still, he recognizes that his translational research may one day help those same patients.

 

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Numerous diseases may have increased C-reactive protein

Many of us have inflammation in our bodies, inflammation that is a potential underlying cause for a great number of diseases. Can we demonstrate the level of inflammation by measuring it? The answer is yes, otherwise I would not be writing this article.

One of the most widely studied biomarkers for inflammation is high-sensitivity C-reactive protein (hsCRP), also referred to as CRP. High-sensitivity means that we can measure levels as low as 0.3 mg/L more accurately.

What is the significance of the different levels? In heart disease, individuals who have levels less than 1.0 mg/L are in the optimal range for low risk of inflammation. Levels of 1-3 mg/L is the average risk range and greater than 3.0 mg/L is the higher risk profile. Above 10.0 mg/L is less specific to heart disease, although still related, but more likely associated with other causes, such as infection and autoimmune diseases (uptodate.com; Diabetes Technol Ther. 2006;8(1):28-36). This biomarker is derived from the liver.

The downside to CRP is that it is not specific to heart disease, nor definitive for the risk of the disease. The upside though is that it may be helpful with risk stratification, which helps us understand where we sit on a risk spectrum, and with progression in other diseases, such as age-related macular degeneration, diabetic retinopathy, depression and autoimmune diseases.

Let’s look at the evidence.

 

Age-related macular degeneration (AMD)

AMD is the leading cause of blindness in patients over the age of 65 (Prog Retin Eye Res. 2007 Nov;26(6):649-673). Therefore, it is very important to help define risk stratification for this disease. In a prospective study, the results showed that hsCRP levels were inversely associated with the risk of developing AMD. The group with an hsCRP more than 3.0 mg/L had a 50 percent increased risk of developing overall AMD compared to the optimal group with less than 1.0 mg/L. But even more interestingly, the risk of developing neovascular or wet AMD increased to 89 percent in this high-risk group.

The significance of wet AMD is that it is one type of advanced-stage AMD that results in blindness. This study involved five studies where the researchers thawed baseline blood samples from middle-aged participants who had hsCRP levels measured. There were more than 2,000 participants with a follow-up as long as 20 years. According to the study’s authors, annual eye exams and lifestyle modifications, including supplements, may be able to stem this risk by reducing hsCRP.

These results reinforce those of a previous prospective study that showed that elevated hsCRP increased the risk of AMD by threefold (Arch Ophthalmol. 2007;125(3):300-305). This study utilized data from the Women’s Health Study, which involved over 27,000 participants. Like the study mentioned above, this one also defrosted blood samples from baseline and looked at follow-up incidence of developing AMD in initially healthy women.

The highest group had hsCRP levels over 5.2 mg/L. Additionally, when analyzing similar cutoffs for high- and low-level hsCRP, as the above trial used, those with hsCRP over 3.0 had an 82 percent increased risk of AMD compared to those with an hsCRP of less than 1.0 mg/L.

Diabetic retinopathy —
a complication of diabetes

We know that diabetes affects significantly more than 10 percent of the population and is continuing to rise at a rapid rate. One of the complications of diabetes affects the retina (back of the eye) and is called diabetic retinopathy. This is a leading cause of vision loss (Am J Ophthalmol. 2003;136(1):122-135). One of the reasons for the vision loss is macular edema, or swelling, usually due to rupture of tiny blood vessels below the macula, a portion of the back of the eye responsible for central vision.

The DCCT trial, a prospective study involving over 1,400 type-1 diabetes patients, showed an 83 percent increased risk of developing clinically significant macular edema in the group with the highest hsCRP levels compared to those with the lowest (JAMA Ophthalmol. 2013 Feb 7;131:1-8). Although these results were with type-1 diabetes, patients with type-2 diabetes are at equal risk of diabetic retinopathy if glucose levels or sugars are not well-controlled.

 

Depression

Depression is a very difficult disease to control and is a tremendous cause of disability. If we can minimize the risk of complications and hospitalizations, this is probably the most effective approach.

Well, it turns out that inflammation is associated with depression. Specifically, in a recent prospective observational trial, rising levels of CRP had a linear relationship with increased risk of hospitalization due to psychological distress and depression (JAMA Psychiatry. 2013;70(2):176-184).

In other words, compared to levels of less than 1 mg/L, those who were 1 to 3 mg/L, 3 to 10 mg/L and greater than 10 mg/L, had increased risk from 30 percent to 84 percent to 127 percent, respectively. This study involved over 70,000 patients.

 

What can be done to reduce
inflammation?

This is the key question, since we now know that hsCRP is associated with systemic inflammation. In the Nurses’ Health Study, a very large, prospective observational study, the DASH diet decreased the risk of both heart disease and stroke, which is impressive. But for this article, in regards to hsCRP, the DASH diet decreased the levels significantly, which also was associated with a decrease in clinically meaningful endpoints of stroke and heart disease (Arch Intern Med. 2008;168(7):713-720).

The DASH diet is nutrient-dense with an emphasis on fruits, vegetables, nuts, seeds, legumes and whole grains and de-emphasis on processed foods, red meats, sodium and sweet beverages.

 

Conclusion

As the evidence shows with multiple diseases, hsCRP is a very valuable nonspecific biomarker for inflammation in the body.

To stem the effects of inflammation, reducing hsCRP through lifestyle modifications and drug therapy may be a productive way of reducing risk, slowing progression and even potentially reversing some disease processes.

The DASH diet is a very powerful approach to achieving optimal levels of hsCRP without incurring potential side effects. This is a call to arms to have your levels measured, especially if you are at high risk or have chronic diseases such as heart disease, diabetes, depression and autoimmune diseases. HsCRP is a simple blood test with easy-to-obtain results.

 

Dr. Dunaief is a speaker, author and local lifestyle medicine physician focusing on the integration of medicine, nutrition, fitness and stress management. For further information, go to the website www.medicalcompassmd.com and/or consult your personal physician.

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With far-reaching technological development, the group works to contribute to new BNL programs

He takes over a team that has had a hand in everything from the creation of video games to the silicon drift detector (which is used in X-ray spectrometry and electron microscopy).

As the recently appointed head of the instrumentation group at Brookhaven National Laboratory, Graham Smith, who has led the Gas and Liquid Detector Group for 15 years, now takes over as the leader of 40 professionals, most of them scientists, engineers and technicians. Smith helps coordinate the development and refinement of technology designed to answer questions ranging from understanding why neutrinos have mass to determining the structure of complex protein molecules.

A part of the Nuclear and Particle Physics directorate, the instrumentation division also works with the other four units at BNL, which include Basic Energy Sciences, Photon Sciences, Global and Regional Solutions and Environmental and Life Sciences.

The division applies some of its work with gas-filled neutron detectors to national security. His group is developing instruments that can “identify contraband material being brought into the country,” which could include uranium or plutonium, he said. Those materials emit neutrons, which are hard to stop, even for a lead-lined shipping container.

“There are only certain materials in nature that are sensitive to neutrons,” he explained. “Hydrogen and Helium-3 are good at stopping thermal neutrons.”

The instrumentation division at BNL has collaborated with professionals in nonproliferation and national security to build neutron detectors that are many pinhole cameras in a single instrument, which can be placed at ports around the country to look for radioactive objects that generate neutrons.

The instrumentation division is also playing an important part in the Long Baseline Neutrino Experiment (or LBNE). The centerpiece of the LBNE will be a liquid argon detector and electronics that BNL’s expertise is making possible, Smith said.

BNL’s Milind Diwan (Power of Three, Jan. 10) has been working closely with the instrumentation group, as well as with the physics, chemistry, accelerator, nuclear engineering and magnet units at BNL.

“The instrumentation division is crucial because they are going to be responsible for the wire chambers and the electronics that must operate at very low temperatures and with a lifetime of several decades without any maintenance,” he explained. “The technological development is far-reaching and extraordinary.”

Diwan is confident the group is up to the task, suggesting that the Instrumentation Division is “considered the best in the world in developing such advanced technologies.”

Smith and his colleagues have also been involved in developing a medical imaging instrument called RatCAP (for Rat Conscious Animal Positron Emission Tomography).

It’s the same principle as a PET scan for humans. The innovation, however, is that it allows an animal to wear the monitor while engaging in its normal activities. Typically, animal PET scans have required anesthesia, to keep an animal still as scientists survey the brain or other areas of the body. The instrumentation group designed and integrated a detector system for annihilation gamma-rays that is compact, lightweight and low power, which benefits from microelectronics.

“When the animal is anesthetized,” suggested Smith, “the brain activity is compromised. The idea is to investigate brain activity without putting the rat under any drug-induced sleep.”

Smith lives in Port Jefferson with his wife, Anne, a teaching assistant at Setauket Elementary School. Their older son, Edward, works in Manhattan in information technology, while their younger son, Michael, is a building manager in Seattle.

The couple enjoy the similarities between the village of Port Jefferson and their home villages in the United Kingdom. They enjoy walking through town, grabbing a cup of coffee, observing the harbor and trekking back.

In addition to the potential professional collaboration with Stony Brook scientists, Smith also appreciates the chance to play squash at the university campus. He met his wife on a squash court when they were at the University of Leicester.

In leading the instrumentation group, Smith said he hopes to continue to create a positive atmosphere that he likens to an extended family.

As for following in the footsteps of William Higinbotham, who invented the video game “Tennis for Two” at BNL in 1958, Smith suggested: “My goal is to provide the motivation for our outstanding staff to continue making significant high technology contributions to new BNL programs, for a better understanding of nature and for an overall benefit to society.”

 

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The effect is based on flavonoids in cocoa and chocolate

Valentine’s Day is one of the wonderful things about winter. For many, it lifts the mood and spirit. A traditional gift is chocolate. But do the benefits of chocolate go beyond Valentine’s Day? The short answer is yes, which is good news for chocolate lovers. However, we are not talking about filled chocolates, but primarily dark chocolate and cocoa powder.

The health benefits of chocolate are derived in large part from its flavonoid content — compounds that are produced by plants. These health benefits are seen in cardiovascular disease, including stroke, heart disease and blood pressure. This is ironic, since many chocolate boxes are shaped as hearts. Unfortunately, it is not necessarily the chocolates that come in these boxes that are beneficial.

Let’s look at the evidence.

 

Effect on heart failure

Heart failure is very difficult to reverse. Therefore, the best approach is prevention, and dark chocolate may be one weapon in this crusade. In the Swedish Mammography Cohort study, those women who consumed dark chocolate saw a reduction in heart failure (Circ Heart Fail. 2010;3(5):612-6). The results were on a dose response curve, but only to a point. Those women who consumed two to three servings of dark chocolate a month had a 26 percent reduction in the risk of heart failure.

For the dark chocolate lovers, it gets even better. Women who consumed one to two servings per week had an even greater reduction of 32 percent. However, those who ate more than these amounts actually lost the benefit in heart failure reduction and may have increased risk. With a serving (1 ounce) a day, there was actually a 23 percent increased risk.

This study was a prospective (forward-looking) observational study that involved more than 30,000 women over a long duration, nine years. The authors comment that chocolate has a downside of too much fat and calories and, if eaten in large quantities, it may interfere with eating other beneficial foods, such as fruits and vegetables. The positive effects are most likely from the flavonols, a subset of flavonoids, which come from the cocoa solids — the chocolate minus the cocoa butter.

 

Impact on mortality from heart attacks

In a two-year observational study, results showed that chocolate seemed to reduce the risk of cardiac death after a first heart attack (J Intern Med. 2009;266(3):248-57). Again, the effects were based on a dose-response curve, but unlike the previous study, there was no increased risk beyond a certain modest frequency.

Those who consumed chocolate up to once a week saw a 44 percent reduction in risk of death, and those who ate the most chocolate — two or more times per week — saw the most effect, with 66 percent reduced risk. And finally, even those who consumed one serving of chocolate less than once per month saw a 27 percent reduction in death, compared to those who consumed no chocolate.

The study did not mention dark or milk chocolate, however this was another study that took place in Sweden. In Sweden, their milk chocolate has substantially more cocoa solids, and thus flavonols, than that manufactured for the U.S. There were over 1,100 patients involved in this study, and none of them had a history of diabetes, which is important to emphasize.

 

Stroke reduction

I don’t know anyone who does not want to reduce the risk of stroke. We tell patients to avoid sodium in order to control blood pressure and reduce their risk. Initially, sodium reduction is a difficult thing to acclimate to — and one that people fear. However, it turns out that eating chocolate may reduce the risk of stroke, so this is something you can use to balance out the lifestyle changes.

In yet another study, the Cohort of Swedish Men, which involved over 37,000 men, there was an inverse relationship between chocolate consumption in men and the risk of stroke (Neurology. 2012;79:1223-1229).Those who ate at least two servings of chocolate a week benefited the most with a 17 percent reduction in both major types of stroke — ischemic and hemorrhagic — compared to those who consumed the least amount chocolate. Although the reduction does not sound tremendous, aspirin reduces stroke risk by 20 percent. However, this study was observational, not the gold-standard randomized controlled trial, like the aspirin studies.

 

Blood pressure

One of the most common maladies, especially in people over 50, is high blood pressure. So, whatever we can do to lower blood pressure levels is important, including decreasing sodium levels, exercising and even eating flavonoid-rich cocoa.

In a meta-analysis (a group of 20 RCTs), flavonoid-rich cocoa reduced both systolic (top number) and diastolic (bottom number) blood pressure significantly: -2.77 mm Hg and -2.20 mm Hg, respectively (Cochrane Database Syst Rev. 2012:15;8:CD008893).These studies involved healthy participants, who are sometimes the most difficult in which to show a significant reduction, since their blood pressure is not high initially. One of the weaknesses of this meta-analysis is that the trials were short, between two and 18 weeks.

 

Why chocolate has an effect

Chocolate has compounds called flavonoids. The darker the chocolate, the more flavonoids there are. These flavonoids have potential antioxidant, antiplatelet and anti-inflammatory effects.

In a small randomized controlled trial comparing 22 heart transplant patients, those who received dark flavonoid-rich chocolate, compared to a cocoa-free control group, had greater vasodilation (enlargement) of coronary arteries two hours after consumption (Circulation. 2007 Nov 20;116(21):2376-82). There was also a decrease in the aggregation, or adhesion, of platelets, one of the primary substances in forming clots. The authors concluded that dark chocolate may also cause a reduction in oxidative stress.

It’s great that chocolate, mainly dark, and cocoa powder have such substantial effects in cardiovascular disease. However, certain patients should avoid chocolate such as those with reflux disease, allergies to chocolate and diabetes. Be aware that Dutch-processed, or alkalized, cocoa powder may have lower flavonoid levels and is best avoided. Also, the darker the chocolate is, the higher the flavonoid levels. I suggest that the chocolate be at least 60 to 70 percent dark.

Moderation is the key, for all chocolate contains a lot of calories and fat. Based on the studies, two servings a week are probably where you will see the most cardiovascular benefits. Happy Valentine’s Day!

 

Dr. Dunaief is a speaker, author and local lifestyle medicine physician focusing on the integration of medicine, nutrition, fitness and stress management. For further information, go to the website www.medicalcompassmd.com and/or consult your personal physician.

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Computer model predicted that sodium would become transparent under pressure, and it does

Finding new materials has been a field where industrious and determined workers mixed elements, hoping to come up with the right combination to form a structure that might meet their needs.

While their choices of ingredients weren’t random, their results often proved disappointing, as the process produced considerably more failures than breakthroughs.

About eight years ago, however, Artem Oganov tried to change that. He didn’t want to build a better workbench or come up with a way to test more materials in a lab. He wanted to come up with a more efficient approach. Armed with a computer and working in an office at Stony Brook University, Oganov hoped to improve the process.

Predicting the crystal structure of an element or molecule in its lowest possible energy state presented an enormous challenge.

“Mathematically, when you formulate this problem, it looks intractable,” explained Oganov.

“The number of possible structures can be boiled down to ten to the power of 20 or 10 to the power of 50. Technically, you can’t sample all those structures,” he continued.

In 2003, Swiss scientists developed a computational method called metadynamics. It provided the first hope that the problem of crystal structure prediction might not be totally hopeless. Still, the process had significant limitations, Oganov said.

Oganov and several graduate students over the years, including Colin Glass, Andriy Lyakhov, Qiang Zhu, Guangrui Qian and Salah Eddine Boulfelfel, attempted to create a computer program that would narrow down those possibilities.

When their first several efforts were unsuccessful, “we were ready to give up.”

By combining several innovative approaches, including uniting global optimization (looking for the most likely solution in the big picture) with local optimization (narrowing the choices down among more subtle differences), they came up with a program that worked.

“The whole trick is to invent an algorithm which can work efficiently and reliably for a nearly infinite size,” he offered. “The problem was so big that we were dreaming without really hoping to get it.”

Oganov’s work has become “the gold standard,” suggested Stony Brook Geosciences Chairman Richard Reeder. “Discovering structures before was kind of random trial and error. There’s no systematic way to do it.”

Using the computer model, Oganov and his team predicted that sodium would become transparent under pressure. They found a collaborator who would conduct the test and, as they predicted, the metal became transparent.

The Oganov lab also became involved in an important discovery about carbon. Under high temperatures and pressure, carbon becomes diamonds. Under the same pressure, but at room temperature, carbon becomes superhard, without turning into diamonds.

Scientists had made guesses about the structure of this superhard carbon, but had trouble narrowing down the list in part because of the low resolution of experimental data. Using his computer model, Oganov predicted its structure. With some experimental support, Oganov’s prediction of a so-called M Carbon proved accurate.

Because other forms of carbon have had applications in technology, Oganov suggested this form might become instrumental in future manufacturing breakthroughs.

Oganov’s discoveries “won’t be seen to be applicable immediately,” Reeder explained, but could impact a wide range of fields, from planetary sciences to drug design.

In his presentations about his work, Oganov includes numerous historical references.

Indeed, if he hadn’t become a scientist, the Russian-born Oganov would have become a historian.

“History,” he explained, “gives very valuable lessons of wisdom: what were the good decisions and the bad decisions people made. How does progress work? History gives you good perspective on that.”

It’s important, he suggested, for people to have historical role models. Some of his include Linus Pauling, whom he described as being the “greatest chemist of the 20th century,” as well as Lev Landau. A physicist, Landau could “throw more ideas on one page than in a whole book written by other people.”

Laudau worked on his couch, scribbling notes that became the basis for papers and books, including one that physicists are still using, Oganov said.

A resident of East Setauket, Oganov would like to become a role model to future generations.

Oganov’s chairman believes he already stands out in his field, not only for his accomplishments but also for his intelligence.

“He’s well on his way. His code is the best out there,” Reeder said. “He has the motivation and the drive to do it.”

 

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A recent journal article highlighted different approaches to weight loss, but ...

In a study published on Jan. 31 in the New England Journal of Medicine, researchers investigate the myths, facts and assumptions associated with losing weight in obese patients (N Engl J Med. 2013;368:446-454). This study has deservedly received a substantial amount of attention, both in the medical news and the layman’s press, such as The New York Times.

The authors brought up really good points, but — and this is the keyword: but — are their conclusions obfuscated or confusing?

Let’s address some of the specific points in the study and the perspective from which they are made. Following are some of the assumptions that they examine.

 

Adding fruits and vegetables to the diet results in weight loss

The authors highlight that this statement is inconclusive. That while fruits and vegetables may be good for your health, they don’t help with weight loss.

But you have to analyze this statement more closely. They are not saying that fruits and vegetables don’t help with weight loss. They say that adding them is not helpful. I agree that if you add these items to a diet of cheeseburgers and fries, you are certainly not going to lose weight.

However, if you shift your diet to one that involves a vegetable-rich, plant-based approach, this has a much different effect than just adding fruits and vegetables without making any other changes. There are a number of studies showing significant long-term weight loss with this type of diet. For instance, in a small, retrospective study, patients on a plant-based, nutrient-dense diet involving a significant amount of fruits and vegetables, lost an average of 33 pounds in the first year and 59 pounds in the second year (Altern Ther Health Med. 2008;14:48-53). Granted, this is not the best-designed study, but it suggests that vegetable-rich diets are effective for significant and sustained weight loss.

 

Slow, gradual weight loss is best for long-term success

The authors debunk this as a myth. However, what do they mean by this statement? Using a meta-analysis, the results show that ultra-low calorie diets are more effective for losing weight than a slow, gradual approach (Int J Behav Med. 2010;17:161-167). This all seems to make sense.

But, the authors compare weight loss of 16 percent to 10 percent over six months. While this may be statistically significant, it is not necessarily clinically rapid versus slow weight loss. For instance, a 200-pound obese patient who loses 16 percent of her weight has lost only 12 pounds more than someone who loses 10 percent of her weight in six months. This is roughly two extra pounds a month.

A diet primarily focused on severe calorie restriction, rather than nutrient density, may work for the short term, but it may throw the homeostasis of the body’s hunger-inducing hormones, such as ghrelin and leptin, into disarray. This creates an environment that may actually cause weight to be regained in the long term (N Engl J Med. 2011; 365:1597-1604).

Another thing to consider is that a low-calorie diet may not necessarily increase life span, as we once thought. This was demonstrated in a study using rhesus monkeys (Nature online Aug. 29). In my Sept. 13, 2012 article, entitled “Calorie restriction disappoints in longevity and quality of life,” I addressed that fact that there may be better ways to lose weight than calorie restriction. One option is the DASH diet, which reduces the risk of heart disease and other chronic diseases (Arch Intern Med. 2008;168:713-720).

 

Bariatric surgery is valuable for some patients for long-term weight loss

The authors conclude that this may be true, and they support their statement with a prospective trial (N Engl J Med. 2004;351:2683-2693). I agree that it may be appropriate for some patients.

But, what is not mentioned is that at least 50 percent of patients who have bariatric surgery tend to regain weight within 24 months, so that the original BMI change is no longer significant (Obes Surg. 2008 Jun;18(6):648-651). There are also significant side effects for some patients who undergo bariatric surgery, such as the dumping syndrome, which can occur especially with high levels of simple carbohydrates in as many as 50 percent of patients, and the inability to properly absorb nutrients, such as B12, calcium, iron and folate (Surgery. 1960;48:185-194; Obes Surg. 2005;15(2):145-154).

 

Weight-loss pills and prepackaged meals may be effective tools

According to the author, weight-loss pills and packaged meals may be the best options for weight loss.

But, the history of weight-loss pills is tarnished. So many of them have been pulled off the market after being approved, because of untoward side effects. Also, once patients discontinue the drugs, they appear to regain the lost weight.

I don’t disagree that diets providing packaged meals are effective ways to lose weight.

But, just like with drug therapy, once patients discontinue the meals, they tend to regain weight. Just like the old saying, it is better to teach a man to fish than to provide the fish for him.

 

Is this study potentially biased?

There may be some bias involved as well, since the authors are not without conflicts of interest. Most of them are associated with pharmaceutical companies as paid speakers, or they consult as well as associate with food manufacturers and prepackaged meal providers. It is true that disclosing this information is important, but take note when reading any study of the authors’ affiliations — they tend to color their perspectives.

 

Benefit of small energy changes

Small, sustained changes in energy-intake or expenditure will produce large, long-term weight changes.

The authors conclude that this is a myth. I emphatically disagree. In fact, last week I wrote about the positive effects of exercise on weight loss. Those that lost the most weight and sustained that loss not only did moderate activities, about 30 minutes a day, four to five times per week, but also were less sedentary the rest of day, as demonstrated by a pedometer (Am J Prev Med. 2012;43(6):629-635).

The authors do bring to light some very pertinent points. They address some other assumptions that really are not based on any scientific evidence. I would encourage people to read the article in its entirety.

But know that not all of the points have been flushed out completely, and keep in mind that the authors have their distinct perspectives and quite a few conflicts of interest.

 

Dr. Dunaief is a speaker, author and local lifestyle medicine physician focusing on the integration of medicine, nutrition, fitness and stress management. For further information, go to the website www.medicalcompassmd.com and/or consult your personal physician.

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Usually kept in check by the body, C. albicans can cause damage for those who are immunosuppressed

This is the second in a two-part series that began last week on two scientists at Stony Brook Medical School who are working to unlock the secrets of different types of fungi that can cause significant health problems.

Like the cracks in the sidewalk that we don’t notice most of the time, Candida albicans is everywhere. Mostly, though, it’s on and around us. While this fungus is harmless much of the time, it has a dark side.

After prolonged catheterization (tubes entering the body) or in people with weakened immune systems, Candida can enter the bloodstream, where it can cause significant damage.

“It’s considered to be the fourth most commonly acquired hospital infection,” explained James Konopka, a professor in molecular genetics and microbiology at Stony Brook Medical School. It often targets the kidney. Even with current state-of-the-art antifungal drugs, Candida can become life threatening.

In most people, Candida often can’t get past the skin or the lining of the gastrointestinal tract. That, however, changes when, for example, patients have surgical procedures.

“A tube going into a patient can provide a site for a biofilm and can get it across the skin,” Konopka explained.

This can also be compounded, he explained, by the use of antibacterial drugs, which eliminate the bacteria and give the fungus more room to grow.

Patients with weakened immune systems, through AIDS, cancer treatments or immunosuppressive therapies, can also be the target of fungal infections.

Konopka is looking from the outside of Candida in, trying to alter the cell wall, or plasma membrane. Everything in the membrane is not randomly moving around, he explained. There are specialized sensors that can be instrumental in its life cycle.

He’s been studying genes that are responsible for 30 proteins in the membrane. He has deleted the genes for most of these proteins and plans to pick the best candidates for more study and drug development.

“If we disrupt the function of those proteins, that leads to a global defect in how the membrane is organized,” he said.

One of the challenges in fungal research is that humans and fungi are more closely related, evolutionarily, than humans and bacteria. On the positive side, that means research into basic cellular mechanisms of fungi may provide information about human cells.

On the downside, however, it provides a tricky type of Venn diagram for medical treatment. Doctors and researchers have to find drugs that only affect fungi and that don’t harm human cells at the same time.

The existing therapies have limitations. As with bacteria, some fungal strains have developed resistance.

Even finding a specific therapy that targets and eliminates Candida could lead to another unintended consequence. Because Candida lives within most of us without causing problems, eliminating all of the fungus could create an opening for an infection from another type of bacteria or fungus.

“There’s been some suggestion that that possibility may be occurring in certain patients in long-term drug therapy,” Konopka acknowledged.

He’s not convinced that’s the case, but it has caused some researchers to think Candida might be filling a niche that keeps worse invaders out.

The ideal therapy may involve a short-term treatment that clears Candida from internal organs, but resets the relationship to where the fungus lives within humans without doing any damage.

At the University of Washington in Seattle, Konopka had been doing basic fungal research under the guidance of Leland Hartwell, who shared the Nobel Prize in 2001 for discovering protein molecules that control the division of cells. When Konopka moved to Stony Brook, he transitioned to studying Candida.

In 2008, he discovered that deleting the proteins in the plasma membranes caused the cell wall to grow backwards.

“There’s a layer of regulation that keeps the cell wall on the inside,” he explained.

Konopka lives in East Setauket with his life, Susan Watanabe, a scientist who is studying HIV, the virus that causes AIDS.

He said he wades out into the water at West Meadow Beach, where he catches bluefish and striped bass.

As for working with fungus, there is an upside: yeast. In the fall, he hosts an Oktoberfest party for his entire building, where he and his guests sample each other’s home-brewed beer. Last fall, the offerings included Strong Island Ale, Rye Smile and Midnight Spice. Konopka provided Hoppy Oktoberfest, a beer he describes as a “classic,” which has “the taste of fresh grown hops, but brings with it a fair amount of sweetness.”

 

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It is possible to overdo exercise for weight loss purposes

When we make our New Year’s resolutions to exercise regularly, the goal for many is to change body composition, to lose weight or at least to maintain weight, but is this reality or myth?

It is a hotly debated topic. You would think the answer would straightforward, since exercise helps us prevent and resolve a great many diseases. For example, in last week’s article, I wrote about the value of exercise before the flu shot in improving immunity.

At the same time, we hope exercise impacts our weight. Does it? This is something that we should know, and rightfully so, before we start exercising. It is important to manage our expectations. There are some new and intriguing studies that address whether exercise has an impact on weight management. The short answer is yes, however, not always in ways we might expect.

Then the questions become: what type of exercise should we be doing, how frequently and for how long? Let’s look at the evidence.

 

Duration

It makes sense that the more we exercise to lose weight, the better, or at least that is what we thought. In a recent small randomized controlled trial (RCT), the gold standard of studies, the results showed that the moderate group in terms of duration saw the most benefit for weight loss (Am J Physiol Regul Integr Comp Physiol. 2012 Sep 15;303(6):R571-R579). There were three groups in the study — a sedentary group (low), a group that did 30 minutes per day of aerobic exercise (moderate) and a group that did 60 minutes per day of aerobic exercise (high).

Perhaps obviously, the sedentary group did not see a change in weight. Surprisingly, though, the group that did 30 minutes of exercise per day experienced not only significantly more weight loss than the sedentary group, but also more than the 60-minute exercise group. The aerobic exercises involved biking, jogging or other perspiring activities. These were healthy young men that were overweight, but not obese, and the study duration was three months.

The authors surmise that the reason for these results is that the moderate group may have garnered more energy and moved around more during the remainder of the day, as sensors showed. The highest exercise group was sedentary through most of the rest of day, probably due to fatigue. Also, it seemed that the highest exercise group ate more than the moderate group, though the difference was not statistically significant. While this study is of impressive quality, it is small and of short duration. Nonetheless, its results are encouraging.

 

Postmenopausal women

As a group, postmenopausal women have considerable difficulty losing weight and maintaining weight loss. In a secondary analysis of a RCT, there were three aerobic exercise groups differentiated by the number of kcal/kg per week they burned: 4, 8 and 12 (Am J Prev Med. 2012;43(6):629-635). All of the groups saw significant reductions in waist circumference. Interestingly, however, a greater number of steps per day outside of the training, measured by pedometer, were primarily responsible for improved waistline circumference, regardless of the intensity of the workouts.

But it gets more intriguing because the group that exercised with the lowest intensity was the only one to see significant weight loss. More is not always better, and in the case of exercise for weight loss, less may be more. This study reinforces the suppositions made by the authors of the previous men’s study: exercise to a point where it is energy inducing and not beyond.

 

Premenopausal women

Not to ignore younger women, those who were premenopausal also saw a significant benefit with weight maintenance and exercise after having intentionally lost weight.

In a prospective (forward-looking) study, young women who did at least 30 minutes of exercise four to five days per week were significantly less likely to regain weight that they had lost, compared to those who were sedentary after losing weight (Obesity 2010;18(1):167-174).

Some of the strengths of this study were its substantially long six-year follow-up period and its large size, involving over 4,000 women between the ages of 26 and 45. Running and jogging were more impactful in preventing weight gain than walking with alacrity. However, all forms of exercise were superior to the sedentary group.

 

Aerobic exercise and resistance training

In another RCT with 119 overweight or obese adults, aerobic exercise four to five times a week for about 30 minutes each was most effective for weight loss and fat reduction, while resistance training added lean body mass. Lean body mass is very important. It does not cause weight reduction, but rather increased fitness (J Appl Physiol. 2012 Dec;113(12):1831-1837).

With weight loss, it’s important to delineate between thin and fit. Fitness includes a body composition of decreased body fat and increased lean muscle mass. To help achieve fit level, it’s probably best to have a combination of aerobic and anaerobic exercise (resistance training). Both contribute to achieving this goal.

In conclusion, exercise can play a significant role in weight, whether with weight reduction, weight maintenance or increasing lean body mass. It appears that 30 minutes of exercise four to five times a week is best. Longer is not necessarily better.

What is most important, however, is to exercise to the point where it energizes you, but doesn’t cause fatigue. This is because it is important not to be sedentary the rest of the day, but to remain active. We should also include a complete package of lifestyle modifications in general — diet, exercise and stress reduction — to get the most compelling results.

 

Dr. Dunaief is a speaker, author and local lifestyle medicine physician focusing on the integration of medicine, nutrition, fitness and stress management. For further information, go to the website www.medicalcompassmd.com and/or consult your personal physician.

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Long term goal is to find drugs that help immunocompromised individuals fight fungal diseases

One of them brews beer, while the other makes his own pizza. While it sounds like a great mealtime combination, what Maurizio Del Poeta and James Konopka do when they’re at work may one day help you or your friends and family.

The two are scientists at Stony Brook Medical School who are working to unlock the secrets of different types of fungi that can cause significant health problems. Del Poeta is studying Cryptococcus neoformans, a fungus that can kill if it reaches the brain, while Konopka is  working with Candida albicans, a fungus that normally lives with and on us but that can also do damage to internal organs, particularly the kidney.

Del Poeta, the pizza maker, has found a drug that targets a sphingolipid on the surface of Cryptococcus that clears the infection in the brains of mice. He recently applied to start testing that drug on humans. That process could take five years.

Konopka, the beer brewer, is targeting a 30-protein sequence in the cell wall of Candida. He is narrowing down the list of targets and hopes to start searching for effective drugs or therapies.

“These two men are superb,” said Jorge Benach, the chairman of the Department of Molecular Genetics and Microbiology. “They are sought after internationally and nationally” to address scientific audiences.

The Molecular Genetics and Microbiology department includes researchers who study viruses, bacteria and fungi. Benach said they are all aware of the potential medical benefit, even as they perform basic research to understand the way these pathogens work.

“It takes a while from what we do to the point where we can save lives,” he offered. “We are on that track. If you hit the ground running, you shorten that distance.”

The Times Beacon Record will profile the research of Konopka and Del Poeta in a two-part series. The Del Poeta feature will run today, while the Konopka story will run next week.

 

Maurizio Del Poeta loves stories. There’s the one about how he met his Italian wife when they were at Duke University. They were, he said with a laugh, two of the only three people originally from Italy at Duke.

He met her at a dinner party after he returned from a ski trip. The only complication: she was dating someone else.

“I was waiting for her to drop this guy,” he laughed. “He wasn’t good for her.”

Six months later, she became single and Del Poeta’s wait was over.

An avid reader, Del Poeta also has a story for a key insight into his research. While reading the late Michael Crichton’s anti-climate change novel “State of Fear,” an ironic choice given his findings, Del Poeta decided he had to test a fungus in a higher carbon dioxide environment, like that in the lung.

He was working with Cryptococcus neoformans, a fungus that is especially problematic in people who are immunocompromised — either through cancer treatments, drugs that suppress the immune system after organ transplants or in people with AIDS.

In the outside environment, a mutant type of this fungus grew normally, but “when you transfer it into the lung, it can’t grow anymore,” he explained.

When he studied it more closely, he found that a specific sphingolipid attached to the surface of the fungus in the mutant prevents it from growing in an environment that has 5 percent carbon dioxide (the concentration in the lung), compared with the approximately 0.4 percent in the atmosphere.

This sphingolipid and the genes and enzymes that lead to its production became a “fantastic target for developing drugs,” Del Poeta offered.

That discovery came in 2005. Del Poeta has spent the last seven years, including the last six months as a professor in the school of medicine at Stony Brook Medical School, looking for drugs that might target that sphingolipid.

He has found several that have worked. The survival rate of animals treated with these targeted drugs is 90 percent, compared with a 100 percent mortality rate when untreated.

Del Poeta submitted a grant to the National Institutes of Health for one of the drugs in February. It received a high score, he said, but it was not funded. After he conducted the promising mouse experiments this year, he resubmitted that grant in the middle of December. He hopes to hear back in the next few months.

The drug not only prevents the spread of an infection in the animal models but it clears the fungus from the brain. Currently in humans, there are no drugs that effectively eradicate the fungus in the brain.

Del Poeta said it may take five years before the drug goes through clinical testing to reach the pharmaceutical shelves.

While the drug is not toxic in animals, it’s unclear what reactions humans might have to it.

Del Poeta got involved in fungal research when he was a medical doctor at Duke. He observed that the patients he had who were immunocompromised, mostly because of AIDS, were dying because of this fungal infection.

He needed “to do something.” He consulted with his mentor John Perfect, who is now the director of the Division of Infectious Diseases at Duke, who suggested he choose between seeing patients and conducting research.

While he misses seeing patients, he finds his research satisfying, especially because of its potential practical impact.

In his research, he combines basic science with the search for drugs.

He explores the mechanism by which the sphingolipid limits the growth of the fungus. He is also looking at ways to boost other parts of the immune system that are not often weakened, even in immunocompromised individuals. He would like to raise the activity level of macrophages, neutrophils and Natural Killer (NK) cells.

A temporary resident of Port Jefferson, Del Poeta and his wife Chiara Luberto, who is studying leukemia at the cancer center at Stony Brook, recently bought a house in Mount Sinai. The couple have two young sons, Matteo and Francesco.

Del Poeta combined his passion for cooking and sharing amusing anecdotes in a cookbook called “Pasta con Amici.”

When he moved to South Carolina (a stop he made before landing at Stony Brook), he missed pizza so much that he built a brick oven with his father. He plans to build another one here, perhaps in 2013.

“I love stories,” he explained. “Behind a story, there is everything. Each of us has a fantastic story.”

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