Conflicting evidence for daily calcium supplementation

Evidence from a recent meta-analysis (September 2015) published in the British Medical Journal goes against the long-standing recommended daily intake of calcium. In fact, one of the lead authors concluded “Most people don’t need to worry about their calcium at all.” His reasoning behind this is that randomized control trials have shown only a slight reduction in risk for fractures with calcium supplementation. At present, the U.S. daily recommended intake for calcium is approximately 1000-1200mg per day. Other countries have different daily recommendations (mostly lower amounts).

The meta-analysis looked at the results from 26 randomized control trials. Some of the major findings include serious adverse events such as kidney stones, gastrointestinal symptoms, and cardiovascular events. It was noted that only two randomized controlled trials evaluated dietary calcium’s effect on fracture risk. Both trials lacked significant power and therefore statistical significance was unable to be achieved.

It is estimated that women lose 0.5% to 1% of bone mass per year after age 40. Calcium supplementation has been recommended for the prevention of osteoporosis.

Previous researchers have expressed concern for the risk of hypercalciuria (elevated calcium in the urine) and hypercalcemia (elevated calcium in the blood) in post-menopausal women. The end result can be the formation of kidney stones. Other meta-analysis have shown an increased for cardiovascular events such as myocardial infarction in those post-menopausal females who take excess supplemental calcium.

There are several points to consider when looking at the results of these studies. While not universally accepted, calcium obtained through a normal diet is likely superior to taking supplemental calcium. Secondly, most need to monitor how much calcium they actually obtain through their regular diet. Some may not need any additional supplementation.

In regards to the newly published meta-analysis, there are additional co-factors, including Vitamin K2 and Vitamin D deficiency which must be considered before concluding that we should not worry about calcium.

Unfortunately, these published findings make it more difficult for clinicians and patients to reach any definitive conclusion regarding daily calcium intake.

This meta-analysis was funded by pharmaceutical giants, Merck, Amgen, Lilly, and Novartis.

 References:

Tai V., Leung W., Grey A., Reid IR., Bolland MJ. Calcium intake and bone mineral density: systematic review and meta-analysis. BMJ. 2015 Sept 29;351.

Gene mapping of the inner ear: Effects on hearing and balance

Hearing loss associated with aging or other disorders is a significant public health problem.

Within the inner ear are specialized sensory cells that include hair cells. Additional supporting cells also contained in the cochlea, provide structural and functional support to the hair cells. Collectively, these specialized cells help detect sound and enable us to hear. Similar specialized cells located in the utricle (pouch near the cochlea) help us maintain balance. This is part of the vestibular system.

These specialized cells are not able to repair themselves or regenerate. Aging along with certain medications, injuries, disease processes, and infections can lead to a loss of hearing and balance problems.

Research scientists from the University of Maryland School of Medicine and scientists from Tel Aviv University Sackler School of Medicine have collaborated in identifying a technique to help isolate a family of proteins that are essential for inner ear cell development.

Historical methods of analyzing gene activity have usually required thousands of cells. In contrast, the research teams, supported by the National Institute on Deafness and Other Communication Disorders (NIDCD) utilized a new technique for analyzing gene activity within one cell. This has allowed the researchers to better understand developmental patterns associated with the inner ear and vestibular system. This new knowledge may help lead to identifying ways to promote regeneration within the inner ear.

In a second study, the researchers used RNA sequencing technology to search for common regulatory regions within the genes expressed in specialized hair cells. They found a group of gene regulators known as Regulatory Factor Xs (RFX) are particularly active in the hair cells. This is believed to play a large part in hearing. In mice who lacked two RFX proteins, loss of hair cells and hearing occurred within 2 weeks after birth. Deafness occurred at approximately 3 months.

 

References:

National Institute on Deafness and Other Communication Disorders (NIDCD)

http://www.nidcd.nih.gov/news/releases/15/Pages/10152015.aspx

A compound related to Vitamin B3 may prevent hearing loss

A recent study published in Cell Metabolism by researchers from Weill Cornell Medical College and the Gladstone Institutes have identified a simple compound that may help prevent hearing loss. The compound nicotinamide riboside (NR) is a precursor to vitamin B3.

Noise induced hearing loss is a problem that can affect anyone at any age. The National Institutes on Deafness and Other Communication Disorders (NIDCD) estimates that more than 26 million Americans between the ages of 20 and 69 suffer from noise induced hearing loss. Hearing loss can result from a one-time exposure to an intense sound or from continuous exposure to loud sounds. Continuous or prolonged exposure to sounds over 85 decibels can cause hearing loss.

The process of hearing is based on a series of events that convert sound waves into electrical signals. Vibrations travel to the inner ear causing wave like ripples within the fluid inside the cochlea. There are tiny hair cells sitting along the top of inner membrane. These hair cells move up and down pushing against the sterocilia which transmits a signal to the auditory system within the brain. It is believed that exposure to loud noise can cause to damage to the junction where the nerves and hair cells meet, resulting in hearing loss.

Previous studies had identified that a chemical compound known as nicotinamide adenine dinucleotide (NAD+), which is chemically related to NR in this study, did protect nerve cells from injury however, it is an unstable compound. Using this information, researchers tested NR in lab mice and found that regardless whether the compound was given before or after exposure, NR did prevent hearing loss. It is believed that NR increases the activity of a protein known as SIRT3 (sirtuin 3) which is located within the mitochondria of the cells and is involved in regulating function.

The results of this study appearing to be promising. The researchers believe that the compound NR may also be useful for treating other disorders that are also mediated by the activity of protein sirtuin 3 such as hypertension, diabetes, and other metabolic syndromes.

References:

National Institutes on Deafness and Other Communication Disorders (NIDCD)

Brown KD, Maqsood S, Huang JY, Pan Y, Harkcom W, Li W, Sauve A, Verdin E, Jaffrey SR. Activation of SIRT3 by the NAD+ precursor nicotinamide riboside protects from noise-induced hearing loss. Cell Metabolism. 2014 Dec 2; 20(6): 1059-1068.

A compound related to Vitamin B3 may prevent hearing loss

A recent study published in Cell Metabolism by researchers from Weill Cornell Medical College and the Gladstone Institutes have identified a simple compound that may help prevent hearing loss. The compound nicotinamide riboside (NR) is a precursor to vitamin B3.

Noise induced hearing loss is a problem that can affect anyone at any age. The National Institutes on Deafness and Other Communication Disorders (NIDCD) estimates that more than 26 million Americans between the ages of 20 and 69 suffer from noise induced hearing loss. Hearing loss can result from a one-time exposure to an intense sound or from continuous exposure to loud sounds. Continuous or prolonged exposure to sounds over 85 decibels can cause hearing loss.

The process of hearing is based on a series of events that convert sound waves into electrical signals. Vibrations travel to the inner ear causing wave like ripples within the fluid inside the cochlea. There are tiny hair cells sitting along the top of inner membrane. These hair cells move up and down pushing against the sterocilia which transmits a signal to the auditory system within the brain. It is believed that exposure to loud noise can cause to damage to the junction where the nerves and hair cells meet, resulting in hearing loss.

Previous studies had identified that a chemical compound known as nicotinamide adenine dinucleotide (NAD+), which is chemically related to NR in this study, did protect nerve cells from injury however, it is an unstable compound. Using this information, researchers tested NR in lab mice and found that regardless whether the compound was given before or after exposure, NR did prevent hearing loss. It is believed that NR increases the activity of a protein known as SIRT3 (sirtuin 3) which is located within the mitochondria of the cells and is involved in regulating function.

The results of this study appearing to be promising. The researchers believe that the compound NR may also be useful for treating other disorders that are also mediated by the activity of protein sirtuin 3 such as hypertension, diabetes, and other metabolic syndromes.

References:

National Institutes on Deafness and Other Communication Disorders (NIDCD)

Brown KD, Maqsood S, Huang JY, Pan Y, Harkcom W, Li W, Sauve A, Verdin E, Jaffrey SR. Activation of SIRT3 by the NAD+ precursor nicotinamide riboside protects from noise-induced hearing loss. Cell Metabolism. 2014 Dec 2; 20(6): 1059-1068.

The Marriage of 3D Printing and Medicine

17th Feb 2015 Hearing, Medical News

The first 3D printer was developed over 2 decades years ago as a means of taking a concept and developing a  prototype that could easily be modified without mass production.  It was believed that 3D printing would revolutionize manufacturing in many different fields.  Now, with continued advancements in 3D printing technology, regenerative medicine, and biological sciences, this unique combination of disciplines coming together is transforming medicine.

Hundreds of thousands prototypes of medical devices and organ tissues are being printed daily.  Based on current medical news and case reports, here are some areas that 3D printing is being used:

Orthopedics– Knee replacements using 3D printing technology are already being used by orthopedists.  Using a CT scan of a knee, hip or other joint, a specific model of the patient’s anatomy is developed. This information is then combined with 3D printing technology to produce a tailored joint replacement and individualized instrumentation.  The true benefit is that patient’s receive an implant that matches with their specific anatomy and not a “mass produced” implant.  It is estimated that there are nearly 30,000 patients who have already received a 3D orthopedic implant.

A 3D printed cast has also been developed to allow for faster bone healing. The device is made of a lightweight, ventilated material (unlike traditional fiberglass casts) and is more conformable to the patient’s specific anatomy.  The manufacturer claims that it can reduce healing time by nearly 40% and improve overall healing rates.

Hearing Aids– There are estimates that there are more than 10 million 3D hearing aids already in use throughout the world.  Patients are reporting increased comfort with in-the-ear type hearing aids that are 3D produced.

Dental Implants– Crowns, caps, bridges, and veneers are being printed using 3D technology.  Current estimates of more than 750,000 3D dental implants worldwide have been used. Digital scans of the patient’s mouth are more accurate than physical molds that have been traditionally used allowing for betting fitting implants.

Prosthetics – Customized prosthetic limbs that match the symmetry and function of the natural limb are being developed.  3D printing has already made a huge impact within the prosthetics and orthotics field. In 2012, a 12 year Haitian boy received the first 3D printed robotic hand.

Spinal Surgery – Surgeons in China successfully replaced the  C2 verterbral body in a 12 year old with bone cancer body using a 3D printed artificial vertebra replacement.  The implant matched the exact shape and form of his natural anatomy which is believed to provide stronger fixation than a traditional titanium implant.

Other spinal manufacturers have developed customized interbody cages and pedicle screw placement guides using 3D printing.

Organ development – This is still in its infancy. The concept of “bioprinting” to develop living tissue structures is advancing.  Researcher’s are seeking to develop transplant-ready organs.  Using a 3D printed organ combined with the patient’s own cells, this has the potential to eliminate transplant lists and treat organs that are failing.

Novel Antibiotic Design to Prevent Hearing Loss

10th Feb 2015 Hearing, Medical News

One of ongoing challenges that modern medicine faces is the treatment of bacterial infections. One of the most widely used class of antibiotics to treat serious infections of the upper respiratory tract, urinary tract, and septicemia are the aminoglycosides.  They are also been used in cases where other antibiotics have failed. Aminoglycosides are used primarily in infections involving aerobic, gram negative bacteria.  While this class of antibiotics offers potent antimicrobial properties, the major side effect is loss of hearing. It is estimated that 20 – 50% of those treated with aminoglycosides develop either partial or complete loss of hearing.  In simplest form, aminoglycosides cause hearing loss by inducing sensory hair cell degeneration in the cochlea (Huth ME, Ricci AJ, Chen AG.  International Journal of Otolaryngology 2011).  This can also result in damage to the vestibular system resulting in ataxia and dizziness.

In a recent study published at the beginning of January, researchers from the Stanford University School of Medicine have developed a modified version of an aminoglycoside that has just as effective antimicrobial properties,  but does not carry the major side effect of deafness. Dr. Alan Cheng and Dr. Anthony Ricci spent over 4 years of research to develop and produce a small amount of an antibiotic, now known as N1MS. This newly patented drug was derived from another aminoglycoside, sisomicin.  N1MS was used to treat a urinary tract infection in mice.  The drug successfully eliminated the infection but did not cause deafness, as other drugs in this class have.  Comparatively, treatment with sisomicin caused 75 – 85% hair cell loss and profound hearing loss in treated mice.  The mechanism of action of N1MS was designed so that it avoids entering into the inner ear cell’s ion channels where deafness is known to occur. The other benefit of this newly designed drug is that it is non-toxic to the kidneys, which is also a known major side effect of aminoglycosides.

The continual development of bacterial resistance to antibiotics and toxicities that are known among the most effective drugs, have created a platform for the development of novel therapeutic agents like N1MS.  The aminoglycosides are subject of further research in the treatment of specific human genetic diseases.

Journal Reference:

Huth ME, Han KH, Sotoudeh K, Hsieh YJ, Effertz T, Vu AA, Verhoeven S, Hsieh M, Greenhouse R, Cheng AG, and Ricci AJ. Designer aminoglycosides prevent cochlear hair cell loss and hearing loss.  Journal of Clinical Investigation. 2015 Jan 2

Dr. Susan Perlman and Stephanie Magness on American Health Journal Nov 7

Dr. Susan Perlman appeared on American Health Journal this Friday to discuss Friedreich’s Ataxia (FA) along with one of her patients, Stephanie Magness. They educated viewers on the clinical aspects of the disease as well as daily life and clinical studies.

Dr. Perlman is a professor in the Department of Neurology at the David Geffen School of Medicine at UCLA and physician specializing in ataxia, Huntington’s Disease, and neurogenetics. She is the Director of the Ataxia and Neurogenetics Program and the Post-Polio Program at UCLA and has been a primary investigator for many Friedreich’s Ataxia trials over the years.

In this program, Dr. Perlman reviews some of the basic facts of the disease – it is a recessive neurogenetic disorder caused by mutations in both copies of the gene that controls the production of frataxin, it is a disease of childhood, and the symptoms start with balance and coordination difficulties. It begins in the legs and progresses to the hands, speech, vision, and even hearing. The patients may also develop cardiac symptoms, which include hypertrophic cardiomyopathy, heart rhythm problems, and even heart failure. Diabetes is another potential symptom and can cause affected individuals to require insulin.

Stephanie Magness is currently one of Dr. Perlman’s patients and, like all too many people with FA, she was not diagnosed correctly for the first few years of her symptoms. Friedreich’s Ataxia is often misdiagnosed as another recessive childhood neurogenetic disease like Charcot-Marie-Tooth disease, cerebral palsy, and idiopathic peripheral neuropathy. She was eventually diagnosed correctly via gene testing and is now able to manage her symptoms accordingly. Stephanie has also taken part in a natural history study as well as a clinical drug trial – possibly the first approved drug for FA.

According to Stephanie one of the most difficult aspects of the disease is its progressive nature. Even if a patient is able to handle their symptoms well currently they know that it may all change. Her advice was to focus on what you can do instead of things that you obviously cannot and find new things to do that you can excel in.

Now that drug companies have begun to take an interest in Friedreich’s Ataxia and to see it as an important area scientifically there is hope that a drug will be approved to treat FA in the not-too-distant future. Watch the program on Vimeo here: http://vimeo.com/110841193 (the section about Friedreich’s Ataxia starts at 15:39)

 

Hearing Loss and Veterans

05th Nov 2014 Hearing, Medical News

One of the most common injuries to war veterans is hearing damage. 60% of soldiers returning from warzones experience some version of hearing damage – either hearing loss, tinnitus, or both. This accounts for around 414,000 US veterans from Iraq and Afghanistan to date. Most people are concerned with loss of limbs, post-traumatic stress disorder, and brain injuries while less attention is brought to hearing loss. Despite its prevalence, hearing damage is often overlooked since it is generally does not cause loss of life.

The two main reasons for hearing damage from war are short-term exposure from high-intensity noise and long-term exposure to loud ambient noise. This can involve everything from loud trucks and helicopters to machine guns, artillery fire, and blasts from explosives. The prevalence and intensity of damaging wartime noises has increased over time, particularly with the use of improvised explosive devices (IEDs), which has resulted in more hearing damage for soldiers than in the past. Hearing protection is provided by the military, but many soldiers will forgo using it in order to listen carefully for signs of danger. In addition – if soldiers find themselves in a combat situation suddenly, there is no time or good way for them to grab hearing protection.

One of the problems with diagnosing hearing loss is that many veterans don’t seek medical attention when they first start to notice problems. Military culture can be partially to blame since hearing loss is so prevalent. Hearing loss has often been seen as a necessary evil or even an honorable sign that a soldier has seen action. However, this delay in treatment is not unique to veterans. Many individuals try to live with their hearing loss, despite the fact that damage to hearing cannot be reversed. On average it takes 7 years for someone to talk to a doctor after they first start noticing changes in their hearing.

Hearing loss is costly for the U.S. Department of Veterans Affairs with around $2 billion in benefits dispersed annually. The VA purchases one in every five hearing aids sold in the United States and 25-30% of all VA disability claims involve hearing. There is a push to get more funding for research in hopes that they can achieve the same innovations that the prosthetic limb field has seen. All veterans are encouraged to have their hearing evaluated upon discharge and medical attention should be sought as soon as hearing loss is noticed.

Starkey Hearing and Doctor Robert Dean Afghanistan Mission

There are many civilians living and working in war zones and, despite not being military personnel, they are exposed to many of the same hazards. There has been significant research done into the effects of war on soldiers, but very little has been done for those not enlisted. Recently it was reported that the number of children and other vulnerable Afghan civilians injured or killed has increased dramatically since the beginning of 2014. There has been a rise in the number of ground engagements in areas with higher civilian populations, which has accounted fro this steep increase in causalities. While civilians can be accidentally injured or killed during war, there has been a disturbing trend of attacks directed toward them – particularly tribal elders or government officials in this case. The number of children and women causalities has increased the most as the fighting moves into areas with higher population density.

Afghan civilians are exposed to everything from gunfire, IED attacks, mortars, and grenades, to loud noises from trucks, helicopters, and aircrafts.  All of these sounds can damage hearing and lead to tinnitus or permanent hearing loss on top of any other injuries.

Hearing damage can occur in one of two ways – long-term exposure to a loud environment (driving a loud truck,) short-term exposure to a high-intensity sound (gunfire or IEDs.) Exposure to loud noise causes destruction of the hair cells in the inner ear, but the degree of destruction is based on the intensity and duration of the noise. These hair cells are responsible for carrying sound vibration information to the auditory nerves, so without them available to convey this information the individuals experience hearing loss.

Hearing loss is irreversible, but there are methods to cope. Hearing aids are the most recommended method to restore some, if not nearly all, hearing to an individual. Starkey Hearing Foundation has been working with the Bayat Foundation  in order to distribute hearing aids to Afghan civilians, many of them children affected by war, who would otherwise be left unable to hear.  We were able to fit over 600 people with hearing aids while on our mission to Afghanistan.