The Calcium Supplement Problem: As Serious As A Heart Attack

© GreenMedInfo

Osteoporosis is not caused by a lack of limestone, oyster shell or bone meal. Heart attack, however, may be caused by supplementation with these exact same “elemental” forms of calcium, according to two meta-analyses published last year in the British Medical Journal.

Back in July of 2011, the British Medical Journal published the results of a high-powered meta-analysis which looked at whether or not calcium supplementation had any effect on cardiovascular disease risk. Indeed, this groundbreaking report, which was based on the results of five clinical trials conducted in the US, Britain and New Zealand, involving over 8,000 people, showed that taking elemental calcium supplements of 500 mg or more increased the relative risk of heart attack by 27%.

Though the study made international headlines at the time, critics soon took issue with the fact that it involved calcium supplementation without co-administered vitamin D. However, in April of that same year, another meta-analysis published in the same journal showed that even with co-administered D elemental calcium increased the risk of heart attack by 24%, and in addition, the composite of heart attack and stroke by 15% — in essence, putting those doubts to rest.

The idea that calcium supplementation may be toxic to cardiovascular health is not new, as many in the field of nutrition have long warned against supplementation with elemental calcium; which is to say, calcium from limestone, oyster shell, egg shell and bone meal (hydroxylapatite). Despite the growing popularity of elemental calcium supplementation, largely reinforced by conventional health “experts” and organizations like the National Osteoporosis Foundation (whose corporate sponsors include calcium manufacturers like Oscal, and Citrical), the habit simply does not make sense. After all, have you ever experienced visceral disgust after accidentally consuming eggshell? If you have, you know your body is “hard-wired” to reject low-quality calcium sources (stones and bones as it were), in favor of getting calcium from food.

Inorganic or “elemental” calcium, when not bound to the natural co-factors, e.g. amino acids, lipids and glyconutrients, found in “food” (which is to say other living beings, e.g. plants and animals), no longer has the intelligent delivery system that enables the body to utilize it in a biologically appropriate manner. Lacking this “delivery system,” the calcium may end up going to places we do not want (ectopic calcification), or go to places we do want (e.g. the bones), but excessively, stimulating unnaturally accelerated cell-division (osteoblasts), resulting in higher bone turn over rates later in life (this is explained in the article below). Or, the body attempts to disburden itself of this inappropriate calcium and keeps it cordained off in the bowel (constipation), or pushes it through the kidneys (stones). Worse, high levels of calcium can ensue in the blood (hypercalcemia), which can contribute to destabilizing the atherosclerotic plaque through the formation of a brittle calcium cap on the atheroma, can contribute to thrombosis (clot) formation, hypertension (that’s why we use calcium channel blockers to lower blood pressure), and perhaps causing arrhythmias/fibrillation and or heart muscle cramping (a rather common, though rarely recognized cause of ‘heart attack’).

The breasts too are uniquely susceptible to calcification, which is why we use the same x-rays to ascertain bone density that we do to discern pathological microcalcifications in the breast, i.e. x-ray mammography. Due to the fact that the hydroxyapatitate crystals found in malignant breast cancer may act as a cellular ‘signaling molecule’ or mitogen (inducing cell proliferation) it is possible that certain breast calcifications may be a cause, and not just an effect, of the tumorous lesions found there. This may also help to explain why women with the highest bone density (often obtained through massive, lifelong calcium supplementation) have up to 300% higher incidence of malignant breast cancer.

“Brain gravel” is also an increasingly prevalent phenomenon, where autoposied patients have been found to have pebble-size calcium deposits distributed throughout their brains, including the pineal gland (‘the seat of the soul’). The wide range of existing calcium-associateted pathologies, and their increasing prevalence in calcium-fixated cultures, demand further investigation and explanation. Could one aspect be our cultural fixation on mega-dose calcium supplementation?

To learn more, read “How Too Much Calcium & Over-Medication Can Break Your Bones

Sayer Ji
Wed, 04 Jan 2012 11:00 CST

The Chemicals In Your Cosmetics

Sodium lauryl sulfate is an effective degreaser used to clean oil stains from the floor of my mechanic’s repair shop; what’s it doing in my toothpaste and my daughter’s bubble bath? And, why is the long-known carcinogen nitrosamine, banned in Canada and the European Union, still a common ingredient in my mascara, concealer, sunless tanning lotion and baby shampoo?

The simple answer is that the U.S. Food and Drug Administration still doesn’t bother to regulate anything it dismisses as cosmetics — any products used topically — despite the growing science showing how easily poisons and pollutants can be absorbed through the skin. Since the 1930s, the only thing the FDA regulates is the accuracy of the labeling on cosmetics.

As long as manufacturers list in gory detail the witches’ brew of industrial chemicals, heavy metals, and toxic substances they blend into your eye cream or face wash, they are free to dump whatever they want into your epidermis.

As consumers, we are left to defend ourselves armed only with unintelligible ingredient labels and confusing news reports about what parts per billion of something can cause cancer or Alzheimer’s. Americans are taking their bodies on a magical mystery tour full of chemicals and heavy metal toxins by way of basic grooming habits.

Just a little Googling reveals that every day we are exposed through personal care products to more than 10,000 nasty chemicals banned elsewhere in the world. Everything from lip balm to hand lotion is filled with stuff we wouldn’t dream of putting in our stomachs. Instead, we eagerly spread it over the largest organ of the body — ensuring effective absorption and exposure to a daily dose of illness-inducing and cancer-causing garbage. The american medicine cabinet has become a virtual love canal of hidden industrial waste that wouldn’t be allowed anywhere else.

For example, the Environmental Protection Agency requires workers to wear protective gloves, clothing, and goggles when handling chemicals like Diazolidinyl Urea and Propylene Glycol when they manufacture your favorite antiperspirant. The EPA warns workers against skin contact with these chemicals because they are known to cause brain, liver, and kidney abnormalities — in concentrations lower than those found in off-the-shelf stick deodorants. By contrast, you are not even given a fair warning by the deodorant industry as it encourages you to apply these very same poisons to your naked underarms every morning.

Okay, so according to Washington it’s every woman for herself, but ever try to read the ingredients of your shampoo? I mean the ingredients that are actually listed? Good luck even pronouncing isobutylparaben. And if “fragrance” is involved you’ll never actually get the straight story. Fragrance is protected as a trade secret and up to 200 suspect ingredients can be buried in there with no call-out.

In a recent Congressional hearing the head of the FDA’s Center for Food Safety and Applied Nutrition, Stephen Sundlof, waved the white flag when he said, “The law as it is currently written allows virtually anything to be incorporated into a cosmetic.” This lack of oversight means that consumers actually know very little about what makes up their make-up. And there is little rigor to the enforcement of existing policies: only nine out of tens of thousands of chemicals have been banned in the U.S., compared to 11,000 so far in the E.U.. Even more alarming is the fact that only 11 percent of ingredients used by Americans in personal care products have even been reviewed for safety — by anyone.

So, what have the Europeans and Canadians figured out that we have not? For one, their governments don’t rely on a voluntary reporting system to monitor product safety. Incidents — from adverse reactions to longitudinal health surveys — are made public by law. Under decades-old U.S. law, cosmetics companies are not required to publicly submit information on the safety of their products so, surprise, they don’t. And the toothless FDA relies almost solely on the Cosmetic Ingredient Review (CIR), the industry’s self-policing safety panel, for its product safety data. European regulators do their own safety research and reporting.

While the poets may consider your body a wonderland, the truth is it’s more likely a wasteland of built-up toxins that would earn perpetrators federal jail time if they dumped it into any canal other than the alimentary.

What we need is a green movement for the human body. Improving consumer protections against “body dumping” must start with the FDA. Fortunately, even with a regulation-averse Congress, much of the FDA’s powers are interpreted internally. There are numerous administrative steps the FDA can take without Congress butting in — if it so motivated by public alarm. You can contact your regional FDA office and make some noise. Several good organizations under the banner of the Campaign for Safe Cosmetics — including the Environmental Working Group and Health Care Without Harm — have been banging the drum in Washington, but they need our help to be effective.

It seems our city sewers have more protections than we do. As a creative alternative, perhaps we could declare ourselves micro-dumps and ask for protections under the EPA. Or we might seek relief from broader protections granted to us under the Occupational Safety and Health Organization (OSHA). Hazmat-clad technicians could scan our ditty bags for offending lipstick and hand creams.

One has to wonder if all this would be different if men wore makeup and a tad more product in their hair.

Source: The Huffington Post,  Estelle Hayes is a Silicon Valley journalist and blogger.

New research: 'Un-growth hormone' increases longevity

SLU scientist says findings could re-frame how to fight aging

A compound which acts in the opposite way as growth hormone can reverse some of the signs of aging, a research team that includes a Saint Louis University physician has shown. The finding may be counter-intuitive to some older adults who take growth hormone, thinking it will help revitalize them.

Their research was published in the Dec. 6 online edition of the Proceedings of the National Academy of Sciences.

The findings are significant, says John E. Morley, M.D., study co-investigator and director of the divisions of geriatric medicine and endocrinology at Saint Louis University School of Medicine, because people sometimes take growth hormone, believing it will be the fountain of youth.

“Many older people have been taking growth hormone to rejuvenate themselves,” Morley said. “These results strongly suggest that growth hormone, when given to middle aged and older people, may be hazardous.”

The scientists studied the compound MZ-5-156, a “growth hormone-releasing hormone (GHRH) antagonist.” They conducted their research in the SAMP8 mouse model, a strain engineered for studies of the aging process. Overall, the researchers found that MZ-5-156 had positive effects on oxidative stress in the brain, improving cognition, telomerase activity (the actions of an enzyme which protects DNA material) and life span, while decreasing tumor activity.

MZ-5-156, like many GHRH antagonists, inhibited several human cancers, including prostate, breast, brain and lung cancers. It also had positive effects on learning, and is linked to improvements in short-term memory. The antioxidant actions led to less oxidative stress, reversing cognitive impairment in the aging mouse.

William A. Banks, M.D., lead study author and professor of internal medicine and geriatrics at the University of Washington School of Medicine in Seattle, said the results lead the team “to determine that antagonists of growth hormone-releasing hormone have beneficial effects on aging.”


The study team included as its corresponding author Andrew V. Schally, M.D., Ph.D., a professor in the department of pathology and division of hematology/oncology at the University of Miami Miller School of Medicine.

Established in 1836, Saint Louis University School of Medicine has the distinction of awarding the first medical degree west of the Mississippi River. The school educates physicians and biomedical scientists, conducts medical research, and provides health care on a local, national and international level. Research at the school seeks new cures and treatments in five key areas: cancer, infectious disease, liver disease, aging and brain disease and heart/lung disease.

The masters of our minds: Meet the brain scientists battling to preserve our sanity

The greatest threat to humanity is all in our minds – Parkinson’s, multiple sclerosis and Alzheimer’s affect millions, while one in six of us will die with dementia. Andrew Preston put squeamishness aside to observe the brain scientists who are on one of civilization’s most ambitious quests: to prolong life itself.

article-1330570-0C2568CD000005DC-403_634x515All is quiet in Room E349 at London’s Hammersmith Hospital but for the gentle whirring of four six-foot-high freezers standing along a side wall. They are very cold-minus 80°C – and behind each is an emergency back-up of liquid CO2, in case the power fails.
Strip lights shine a chill, white light down onto the sparse contents of the sterile air-conditioned room. There are two steel sinks, a computer monitor, a microscope and four shelves upon which  identical white plastic containers are lined up, their lids firmly on, each one numbered in black marker pen. A large steel bench straddles the center, and is perforated for drainage and cleaned by a steady down-drought, which sucks any vapors or smells down and away. On it sit two cutting blocks, each with a triangular guide frame, a sharp knife, a scalpel, blue tweezers and several turquoise plastic sample cases. The silence is broken at 10am when neuropathologist Dr Federico Roncaroli and neuroscientist Dr Steve Gentleman use their swipe passes to enter through the blue security doors. They put on disposable plastic overalls and purple nitrile rubber gloves, reach into a container, numbered 4273 and 4563, take out the contents, place them on the cutting block and pick up a scalpel.

article-1330570-0C24C6E5000005DC-215_634x430 They are here to help advance a vital cause. To identify, delay, and perhaps eventually prevent the onset of devastating illnesses that will affect increasing numbers of us as the population ages:  principally Alzheimer’s, dementia and Parkinson’s disease. They will also observe the damage inflicted on our brains by our “lifestyle choices”: smoking and drinking. To do this they must dismiss any thoughts of squeamishness they might have at the sight of the organ before them and at the thought of what they must now do to it.

The human brain is heavier than you might expect. It weighs in at 3lb – that’s two per cent of the body weight of an average person – and consists of water, fat and protein. It is a tightly packed housing of 100 billion neurons, or nerve cells, which siignal to each other by generating and passing on electrical signals. These shuttling signals coordinate every action of the body and produce every thought, memory and feeling. But what we know about how the neurons do this is dwarfed by what we do not know.


When we are born, our brains are a quarter of their eventual adult size; by the age of one that rises to 75 per cent and it is almost full size by the age of eight. But from the age of 20, that goes into reverse: it decreases by about 1g per year.

Advanced imaging techniques (like CT and MRI scans) have built up a picture of the anatomical structures inside the living, working brain. Others (like PET and fMRI scans) have gone further, revealing how the brain functions by showing which parts are firing. This is done by measuring alterations in blood flow and glucose absorption. But like a man reporting from the Moon’s surface rather than inspecting it remotely with a telescope, the biggest understanding comes from examining the real thing.

Once out of its container, the brain’s coiled mass of beige, gelatinous wrinkles looks strangely beautiful. It is rubbery and firm to the touch. It’s unnerving when you realize that the person this came from was alive just a few weeks earlier.

Dr Gentleman, however, is entirely pragmatic.

“I absolutely don’t feel squeamish,” he says. “It’s out of context, isn’t it? I have huge problems in equating this to a person. Instead I see it as a route to finding a cure.”

The brain tissue bank at Hammersmith run by Imperial College has 20 freezers and currently holds 400 brains from people who had Parkinson’s, 503 multiple sclerosis brains and 90 “control” brains. The control brains don’t have, or at least don’t appear to have, any evidence of disease and so can provide scientists with a basis for comparison.

Major progress in this science has only been made relatively recently. The Egyptians would discard the brain before mummifying a body, while to Aristotle it was a mere secondary organ. To him it helped cool the heart, which he regarded as the most important organ. It was only life-changing accidents like that of American railway foreman Phineas P Gage that helped give a picture of how the brain works.

Gage survived an explosion in 1848 in which an iron rod was driven into his head. He went from being a quiet, good-natured and reliable worker to surly, “grossly profane” and unable to hold down a job. From this, doctors and scientists came to realize that specific brain areas control personality and behavior, in this case the brain’s frontal lobe.


The case of Henry G Molaison helped further. In 1953 surgeons removed an extensive area of the hippocampus, towards the back of his brain, in order to halt severe epilepsy. From then on everyday events would stay in his mind just fleetingly, and whenever he met people he already knew he didn’t recognize them. This helped lead to the realization that the hippocampus is vital for memory storage, as well as spatial navigation. It is an area attacked by Alzheimer’s disease.

Dr Alois Alzheimer discovered the disease in 1906 after examining the brain of a woman who died in her fifties and had suffered short-term memory loss. Now some 820,000 people suffer with dementia in the UK (two-thirds of them with Alzheimer’s), which costs the country an estimated £23 billion in NHS and social care, and the work of unpaid carers. The number of people affected is predicted to double in the next 30 years, largely because we are living longer.

“Research using brain tissue remains vital to help us halt the progress of diseases like Alzheimer’s,”  says Dr Safa Al-Sarraj of King’s College Hospital, London, which coordinates the Brains for Dementia research network of five tissue banks. It’s an uphill struggle though: for every £1 spent on cancer research, only 8p is spent on dementia.

article-1330570-0C24C535000005DC-847_634x404While a cure for the disease remains a distant prospect, there is still hope that research to combat Alzheimer’s and other neurological disorders like Parkinson’s disease and multiple sclerosis might help us live longer.

“Research is like doing a 5,000-piece jigsaw without the picture,” says Dr David Dexter, director of the MS Society/Parkinson’s UK tissue bank run by Imperial College.

“You start with the boring bits, putting down the straight edges, which is what scientists have been doing for the past few years. The jigsaw for Parkinson’s is really coming together now, and very interesting and novel therapies are starting to come out that wouldn’t be happening if we didn’t have the brains on which to do research.”

“My bleeper went off at 5am on Saturday,” says Dr Dexter. “It was news from his stepson that a registered donor had died in East Anglia. A GP signed the man’s death certificate, which was fortunate because normally GPs on call at the weekend won’t sign if it is not one of their patients. We then approached the local hospital to see if they had on-call mortuary staff. The man had died not far away from Ipswich and the facilities manager there said he was willing to come in – we pay mortuary staff £100 to take the tissue out.”
article-1330570-0C24C5DF000005DC-90_634x344“Fresh” brains, and if possible the spinal cord, are especially prized, because if frozen immediately scientists can preserve all of their structures, enzymes and genetic information. But the race to get a brain to the tissue bank within 24 hours is fraught and relies on a lot of things falling into place. First as a donor you need to be registered; then a GP and local hospital and funeral staff need to be available, so Sundays can be a problem.
“We liaised with the family to move the body from home to Ipswich,” continues Dr Dexter. “At the same time one of our technicians jumped on a train from London. His job was to bring the tissue back to the brain bank here in a leak-proof metal container surrounded by ice blocks in what looks like a picnic bag.”

‘They travel with documentation explaining what they are carrying, but we have had problems in the past bringing tissue by plane back from Northern Ireland. The containers had to be opened up and inspected because, on X-rays, brain tissue shows up the same as Semtex plastic explosive.”

Normal organ donor cards do not cover brains. Celebrity donors have helped raise awareness – those to have signed up to donate include Jeremy Paxman and Jane Asher, whose brother-in-law has Parkinson’s – but brain banks do still need new pledges.

article-1330570-0C24C74B000005DC-574_306x304“Control” brains are in particularly short supply, and for research into Parkinson’s, for example, Imperial College needs donations from different ethnic groups -“ as well as people with younger-onset disease, diagnosed under the age of 45, who are prepared to have their brains monitored as the disease progresses.

The purpose of the brain bank is twofold: to provide tissue for research projects and for the detective work of its neuropathologists, who can offer a definitive post-mortem diagnosis. Approximately 17 per cent of people diagnosed with Parkinson’s are later found not to have actually had the disease once brain tissue is examined.

Although a definitive diagnosis can only be made once cells have been looked at under a microscope, even during the initial cutting some clear signs of disease can be spotted.

“In the case of Alzheimer’s you’re looking for shrinkage mainly and the troughs on the surface would become wide and the crests narrower,” says Dr Gentleman from Imperial College. In some cases the decay can be so extreme that the relatively smooth surface can be transformed to look like a moist, overgrown walnut.

“With Parkinson’s disease, a major area we look at is the thumbnail-sized substantia nigra, which, as the name suggests, should show black pigmentation.”

If the dark pigmentation has turned pale this means there has been a degeneration of cells that help control muscles and movement, explaining the tremors and motor problems associated with the disease. Evidence of multiple sclerosis can appear as lesions or scars showing damage to the myelin, the fatty insulation around the axons in the nerve cells that helps messages travel quickly and efficiently.

Once at the lab the “fresh” brain is cut in half, sliced into 1cm thick slices, and samples taken which are snap-frozen for future research using supercooled liquid isopentane. This freezes the tissue very rapidly ready for storage so that whenever it is used in the future all the cells are perfectly preserved, with DNA and RNA information (the two of which make up the genetic material of cells) intact.

The other half is put in formalin, to preserve it. A few weeks later this tissue is cut into 1cm-thick slices and 2cm-square blocks and put into small plastic cases. These blocks are then “processed” with a variety of fixative liquids before being embedded in paraffin wax.

Once set, thin sections, just six microns across (that’s six-millionths of a meter, even thinner than a red blood cell, which is eight microns wide) are taken from the block using a microtome (known among hard-headed staff as “the bacon slicer”). The slices are put on a slide and are then ready for microscopic analysis, including staining with colored dyes or antibodies, which can show up evidence of disease and help with making a diagnosis.

Research has proved that size doesn’t matter when it comes to brains; the way a brain is wired inside is far more important. Dr Dexter remembers technicians having a running game trying to guess the sex of the brain just by looking.

“Female brains generally, but not always, are slightly smaller,” he says, “but that is in proportion to body size. They have more or less the same number of neurons but these are packed into a smaller space. The brain is quite a sexually dimorphic structure though – women are more susceptible to stroke, whereas men are more susceptible to Parkinson’s disease.”

And what about unusual brains? Would he, for example, be able to recognize the brain of a genius?

“I don’t think you would really see any differences – if you put Einstein’s brain in front of us, we wouldn’t know it was his,” says Dr Dexter.

“The difference between a computer now and a computer in the early Nineties is the connections, and the brains of humans are similar,” agrees Dr Al-Sarraj.

article-1330570-0C24CC28000005DC-591_306x301“We have the same number of neurons – our brains had the same number of neurons when the Pharoahs were around – but the connections in our brains and the synapses (the gaps between neurons bridged by chemicals called neurotransmitters) now work much better. We can correlate things better and understand things better. That’s why Einstein’s brain is different… he could see and understand things I cannot understand – the connections in his brain were different to mine.”

Samples taken from brains are used to investigate correlations between clinical symptoms and post-mortem findings, possible genetic causes and predispositions to disease, and to evaluate new drugs.

“Cure is quite an emotive term,” says Dr Dexter, of research into Parkinson’s. “Basically I think the first goal is to keep people at the level at which they are when they are diagnosed. Once we

can find out who is going to develop the disease then if you apply a treatment early enough you may be able to prevent it. Finding the mechanisms has to be done with tissue itself, and animals don’t suffer from Parkinson’s, so that means human tissue.

“Ten years ago we didn’t know the mechanism behind the dying of cells, but now we have clues. At the moment we can treat Parkinson’s symptoms, but clinical trials start next year on treatments to stop cells dying and slow the disease down.”

“Ideally we need to diagnose the disease before it becomes clinically obvious, by which time a lot of the damage has already happened,” adds Dr Gentleman. “Our realistic aim is to stop whatever the underlying process is. I think it’s way into the future that you’ll actually be able to reverse any changes.”

article-1330570-0C1DF6CA000005DC-878_306x841Progress, however slow, also continues to be made into tackling Alzheimer’s – the development of current drug treatments for dementia would not have been possible without studying brain tissue.

“With a donation of a heart you see an immediate benefit, but with the brain it takes time,” says Dr Al-Sarraj.

“There are research projects which are about to break through to halt the progress of Alzheimer’s. Then you would at least be able to plan your life while you still have some mental capacity. If we can stop its progress then it could become like diabetes so that people can live with it. I will be 60 in a few years’ time and if I get dementia I will be out, but maybe in the next generation people will get dementia but be able to deal with it and keep working for a further 15 or 20 years. ”

Dr Al-Sarraj will donate his brain for research, as will Dr Dexter.

“Years ago there was a lot of bad publicity about organs being taken without consent,” says Dr Dexter, “but since the Human Tissue Act in 2004 everything is now much more regulated.”

“If you tell the public the truth, take the mystery out of it and explain exactly why it’s important to donate, then I’m sure more people would sign up. I think once I’ve finished working here I would donate. But if I died while I was still here then I would be asking my colleagues to dissect me and I don’t think that’s fair.”

In the meantime, do they have any tips on how to look after our brains?

Dr Dexter has one strong piece of advice, thanks to a sideline of research he is doing into “Italian binge-drinking rats”: watching the damaging effects this has on the hippocampus of their brains, and hence on long-term memory. From his research so far he can safely say “binge-drinking appears to have a hugely harmful effect on the brain”.

As for looking after his own, he admits, “I take flavonoid pills which I get from America, including tangeretin, which is present in the peel of tangerines, and which protects neurons and can slow down the aging process, and also selenium which boosts the immune and anti-oxidant system.”

Both Dr Dexter and Dr Al-Sarraj claim exercise and keeping an active mind are important.

“If once you stop working you don’t do anything you could succumb to neuro-generation quickly”™ claims Dr Al-Sarraj.

“Keep yourself busy and mentally agile by exercising your brain. You need to be challenged as a person. As for supplements like antioxidants and vitamins we need to know more. I don’ t take any but if you go to a conference of neuroscientists, people won’t actually openly say they take anything to keep their brain in good order. But ask anyone there who doesn’t take them to put up their hand, and no hands will go up.”

As he respectfully places the remaining brain tissue back in its container in Room E349, the dissection complete, Dr Gentleman points out yellowy deposits on a blood vessel going into the base of the brain, which could be signs of a high fat diet or smoking. His advice is moderation.

“Don’t smoke, obviously, plus think about diet and exercise. In the Alzheimer’s field it’s becoming clearer that it’s those general lifestyle factors that affect your subsequent risk of deterioration. It’s not going to protect you completely but you do lower the risk.”, By Andrew Preston

Potential Found in a New Approach to Alzheimer's

A potentially promising approach to treating Alzheimer’s disease has been developed by researchers studying sirtuin, a protein thought capable of extending lifespan in laboratory animals.

Using mice prone to developing Alzheimer’s, the researchers showed that activating sirtuin suppressed the disease and that destroying sirtuin made it much worse.

The finding was made by Gizem Donmez, Leonard Guarente and colleagues at the Massachusetts Institute of Technology, who say it raises the hope of treating Alzheimer’s, and possibly other neurodegenerative diseases like Parkinson’s and Huntington’s, with drugs that activate sirtuin.

Researchers not involved in the study agreed. “We think it is a scientifically compelling story that ties the sirtuins to the biology of Alzheimer’s disease,” said Dr. Dennis J. Selkoe, an Alzheimer’s expert at Harvard Medical School. But the therapeutic implications, Dr. Selkoe added, “remain quite up in the air.”

Another expert, Dr. Juan C. Troncoso of Johns Hopkins University School of Medicine, said the finding “opens a very good avenue, but it’s not without a lot of technical challenges.”

Drugs that activate sirtuin already exist, including resveratrol, a minor ingredient of red wine and other foods, and small-molecule chemicals designed to mimic resveratrol. Sirtris, the company that developed the drugs, is testing them against diabetes and other diseases. This generation of drugs does not cross the blood-brain barrier so would not work against Alzheimer’s.

But George P. Vlasuk, Sirtris’s chief executive, said the company had developed other sirtuin-activating chemicals that do reach the brain and are in preclinical trials. “We think it has very significant potential in neurodegenerative diseases,” Dr. Vlasuk said.

Sirtuin has been the subject of intense research in the last few years because it seems to protect the body’s various organs against disease by stepping up maintenance programs. The substance came to light through studies of longevity, particularly the discovery that reduced-calorie diets could lengthen the lifespan of mice by 30 percent. Sirtuin appears to convey much of the beneficial effect of such diets, even though drugs that activate sirtuin have not yet been shown to prolong mice’s lifespan in experiments.

Dr. Guarente, a leading sirtuin researcher, said the protein’s protective power against other diseases made him wonder if it might also help against Alzheimer’s. He obtained mice that tend to develop Alzheimer’s-like symptoms because they are genetically engineered to carry two mutated human genes that cause a buildup of plaque in the brain. The mice were crossed with a strain of mice in which the sirtuin-making gene is particularly active. They were also crossed with a strain in which the sirtuin gene was deleted entirely. Dr. Guarente’s team could thus test the effect of having either more or less sirtuin in the brains of Alzheimer’s-prone mice.

The decline in memory typical of Alzheimer’s “was clearly suppressed” in the Alzheimer’s-prone mice with abundant sirtuin, the M.I.T. group reports in Friday’s issue of Cell, while the mice with Alzheimer’s genes and no sirtuin started to lose memory at a much younger age.

The team found the sirtuin protected the mice’s brains two ways. First, it activated a system called the notch pathway, which protects brain cells against stress. Second, it enhanced an enzyme whose activity avoids the buildup of the plaque characteristic of Alzheimer’s and particularly of a toxic component called A-beta peptide.

Reducing the amount of A-beta peptide is helpful only in Alzheimer’s but turning on the notch pathway could provide general protection for the brain. Activating sirtuin, the M.I.T. researchers conclude, “is a viable strategy to combat Alzheimer’s disease and perhaps other neurodegenerative diseases.”

Dr. Guarente said he was looking into whether extra sirtuin had an effect in mice made vulnerable to Parkinson’s and Huntington’s disease.

Activating the notch pathway with sirtuins “opens a lot of options,” Dr. Troncoso said. “If we can activate the same gene we may provide a tonic for nerve cells under stress, and that may be of use in other diseases such as Huntington’s and Parkinson’s in which the nerve cells degenerate,” he said.

Sirtuin research is a highly active field but one whose ultimate benefit remains to be seen. The sirtuins seem to be powerful players in maintaining the body’s health, but many aspects of their behavior are still unclear.

Also unclear is whether sirtuin’s protective effects can be elicited by drugs instead of by the usual natural stresses, like lack of nourishment. There are continuing disputes as to whether resveratrol activates sirtuin directly or indirectly. Much may depend on a Phase 2 clinical trial of resveratrol with Type 2 diabetes. The results of the trial should be known later in the year, Dr. Vlasuk said in an interview last month.

Should resveratrol prove ineffective, Sirtris has two small-molecule chemical drugs, known as 2104 and 2379, which are also in clinical trials. The chemicals can be given in much smaller doses than resveratrol. There have been no safety issues with any of the drugs, Dr. Vlasuk said, with the possible exception of a multiple myeloma trial, using very high doses of resveratrol, in which several patients developed a symptom common with the disease. The trial ceased new enrollment of patients in May.

The New York Times, July 23, 2010

Pharma seeks genetic clues to healthy aging

Scientists believe people who live to 100 years or more hold valuable secrets in their genes that can reveal targets for medicines to tackle a wide range of age-related diseases, as well as improving longevity itself.

“If you make it to 100, you must have had good health and a good life — otherwise you wouldn’t be at the tail end of the age distribution curve,” Kaare Christensen of the Danish Aging Research Center told Reuters in an interview.

“So basically, we’re trying to figure out how they do it.”

Of course, genes are not the whole story: experts believe genetic factors account for a only fraction of longevity. Other factors like a healthy lifestyle, good diet and safe environment combine to play a role in determining when we die.

Yet so-called “longevity genes” certainly exist, and their importance grows the longer a person lives, so identifying them and finding out what they do to fight off killer diseases is a hot area of research.

With lifespans already increasing at a breathtaking rate — an average of three months is being added to life expectancy every year at the moment — scientists stress that a “magic pill” to help people live ever longer is not what anyone should be seeking.

Instead the aim is known as “compression of morbidity” — improving the health of rapidly aging populations and squeezing to a minimum the amount of time at the end of their lives when they are sick, in pain, or dependent.

“None of us, probably, wants another five years in a nursing home,” said Linda Partridge, director of University College London’s Institute of Healthy Aging.

“But an additional five years without any particular health problems would be another matter.”


One thing is sure: the pool of people to work with is growing fast. There are around 450,000 centenarians in the world today and experts estimate that thanks to aging baby-boomers, there could be a million across the world by 2030.

Genetic science and technology is developing rapidly too, allowing scientists to scan the genes of the super-old in search of the secrets of long life — and drugs to mimic them are starting to appear.

“The drug companies have got lots of patents out on some of these targets,” said Partridge. “Nothing has actually emerged yet, but they are clearly working on them.”

Until recently, only one candidate had shown any promise as a potential “longevity gene.”

It is known as APOE. On the one hand, its variants have been linked with an increased risk of heart disease and of developing the brain-wasting disease, Alzheimer’s. On the other, it is associated with a greater chance of a longer, healthier life.

Scientists have found that a particular variant known as APOE4, which gives carriers a higher risk of developing Alzheimer’s and heart disease, is about 50 percent less common in centenarians than in younger people, suggesting that those without it are more likely to live longer.

Other “longevity gene” candidates are now starting to emerge, including one called FOXO3A and another called humanin, both of which have links to the body’s insulin pathways.

With them comes more evidence that genes associated with long life are also linked to decreased risk of major killers like heart disease, Alzheimer’s and diabetes.

Nir Barzilai of the Albert Einstein College of Medicine at Yeshiva University in New York has been conducting studies with a group of several hundred centenarians in the United States to see if he can find gene patterns that can be chemically copied.

“We are assuming that the 100 year-olds are enriched with longevity genes,” he said in an interview. “And when you find genes, you discover the pathway, and then you can try to modulate the pathway with drugs.”

As well as with the humanin gene, his team has been working with variations of a gene known as cholesteryl ester transfer protein, or CETP, which they have linked to long life, good heart health, a reduced risk of cognitive decline with age, and a smaller chance of developing Alzheimer’s disease.

Drug companies are already targeting the CETP gene with an eye to helping prevent heart disease by upping so-called “good” or HDL cholesterol.

The U.S. drugmaker Merck & Co, for example, has a CETP drug in late-stage clinical trials to test its effectiveness in raising good cholesterol.

But Barzilai thinks it may turn out to do much more than that: “We believe that once this drug is out it could be the first drug to be used as an anti-aging drug,” he said.

Swiss pharmaceutical company Roche also has a CETP drug, called dalcetrapib, in late-stage clinical trials in partnership with Japan Tobacco, in which it sees great potential.


The emerging link between long life and disease resistance has already been seen in animal experiments.

Last week, British scientists found in experiments with laboratory worms that the DAF-16 gene, similar to FOXO genes in humans, is linked to aging and immunity.

And several studies have shown that when scientists successfully target the underlying aging process to make an animal live longer, they also protect them against aging-related diseases.

Resveratrol, a drug being developed by Britain’s GlaxoSmithKline and based on a compound found in red wine, has been shown in studies on mice to give them longer and healthier lives.

And the antibiotic rapamycin, sold under the brand name Rapamune by Pfizer and designed to suppress the immune system in transplant patients, has also been shown to slow age-related disease and extend life-span in mice.

“These things are all very interwoven in each other,” said Christensen.

Partridge also sees this as a sign that some medicines now on the horizon may be bigger hitters than previously thought.

“What it shows very clearly is there is an underlying aging process which acts as the major risk factor for aging-related diseases, and if you can somehow ameliorate its effects, then the animals become relatively disease-free,” she said.

“They (the drugs) may be being developed specifically for dementia, or cancer, or some specific age-related disease, but the biological research is telling us that they’re probably going to turn out to have surprisingly broad-spectrum effects.”

Reuters: Science