Richard G. Petty, MD

Mature Plasticity in the Human Brain

The more we look, the more we understand that the human brain retains a remarkable ability to learn and re-fashion itself well into old age. The old idea that young brains are flexible, but that age causes us to become “hard-wired” and inflexible is not correct.

This has been confirmed in some new research that has just been published in the journal Neuron by investigators from Johns Hopkins who have shown that adult neurons are not glued in place as rigidly as had been thought.

The investigators led by David Linden used a new technique known as two-photon microscopy that allowed them to living neurons at work in the intact brain. The researchers injected fluorescent dye into the brains of mice to illuminate a subset of neurons and then viewed these neurons through a window in the skull of living, anesthetized mice.

They examined neurons that extend axons to the cerebellum, a region of the brain involved in coordinating motor and sensory information. These axons have a primary trunk that runs upward and several smaller branches that sprout out to the sides.

While the main trunk was firmly connected to other target neurons in the cerebellum, the side branches were mobile: Linden describes them like this:

"The side branches swayed like kite tails in the wind."

Over the course of a few hours, individual side branches would highly dynamic behavior, elongating, retracting and morphing. These side branches also failed to make conventional synaptic connections with adjacent neurons. The motion of the side branches was arrested stalled by a drug that produced strong electrical currents in the axons.

Why the brain would want such motile, non-connected branches remains a mystery.

They may provide a second mechanism for conveying information beyond traditional synapses. Alternatively they may be involved in nerve regeneration.

Whatever the final answer, it is clear that the adult brain remains a remarkably plastic, fluid and flexible structure.

Excellent news for all of us!

“That which is flexible and flowing will prosper and grow. That which is rigid and blocked will wither and die.”
--Tao D Ching

“When a noble life has prepared old age, it is not decay that it reveals, but the first days of immortality.”
--Muriel Spark (Scottish Writer, 1918-)

"You will stay young as long as you learn, form new habits and don’t mind being contradicted.”
--Marie, Baronin von Ebner-Eschenbach (a.k.a. Baroness Marie von Ebner-Eschenbach, Austrian Writer, 1830-1916)

Your Brain's Inertial Navigation System

There are many mysteries about the human brain. One is the role of the cerebellum that lies at the back of your head right underneath the cerebral hemispheres. Most students believe that it is only involved in balance and motor coordination, but that does not make much sense: relative to the rest of the brain, humans have the largest cerebellum of any species apart form the dolphin. And there are good reasons for believing that it is involved in the coordination of emotional and social processes, as well as language.

We now learn that it may have yet another function. Colleagues from Washington University School of Medicine in St. Louis report that there is a sophisticated neural computer that is buried deep in the cerebellum, that performs inertial navigation calculations to calculate our precise movement through space.

These calculations are incredibly complex and involve the vestibular system in the inner ear that provides the primary source of input to the brain about the body's movement and orientation in space. However, the vestibular sensors in the inner ear only give us information about the position of our head position. In addition the vestibular system's detection of head acceleration cannot distinguish between the effect of movement and that of gravitational force.

Dora Angelaki and her team based their brain studies on the predictions of a theoretical mathematical model. The model proposed that the brain could calculate inertial motion by combining two things:
1. Rotational signals from the semicircular canal in the inner ear with
2. Gravity

Based on previous research, they concentrated their search for the brain's inertial navigation system on particular types of neurons called Purkinje cells, in a region of the cerebellum known to receive signals from the vestibular system. This region is known as the posterior cerebellar vermis, a narrow, worm-like structure between the brain's hemispheres. It has been known for two centuries that damage to the cerebellar vermis can produce bizarre neurological problems.

In their experiments, the researchers measured the electrical activity of these Purkinje cells in monkeys as the animals' heads were maneuvered through a precise series of rotations and accelerations. After analyzing the electrical signals measured from the Purkinje cells during these movements, the researchers concluded that the specialized Purkinje cells were, as predicted, computing earth-referenced motion from head-centered vestibular information.

This is a remarkable finding: the cells are able to make complex deductions based on very little information.

Cells in the brain, particularly cells of the Purkinje type are designed to adapt and learn. So the finding gives yet more credence to the idea that balance, coordination and orientation in space are learnable skills. That will be the topic of another research project.

But for now, the evidence suggests that anything that helps you to practice these skills will likely pay dividends as you get older.

Zen and the Aging Brain

The two main kinds of meditation that have received a lot of research attention are Zen and Transcendental Meditation. Both produce measurable physiological changes and both may produce changes in the brain.

Zen meditation is centered on attentional and postural self-regulation.

As we age, there is normally some decline of cerebral gray matter volume and attentional performance. As I have pointed out, those changes do not necessarily mean a decline in functioning, but simply a change. 

In a new study researchers here in Atlanta examined how the regular practice of meditation might affect the brain. The researchers studied 13 regular practitioners of Zen meditation and 13 matched controls.

They used some sophisticated techniques to calculate the volumes of different regions of the brain. They also performed a computerized sustained attention task.

While the control subjects showed the expected negative correlation of both gray matter volume and attentional performance with age, the meditators did not show a significant correlation of either measure with age.

Interestingly, the effect of meditation on gray matter volume was most prominent in a region of the brain called the putamen, a system of the brain that is strongly implicated in attentional processing.

These findings are intriguing and are consistent with some of the research done in Richard Davidson’s laboratory in Wisconsin, that looked at people practicing a different form of meditation, but also showed that expert meditators produce both structural and functional changes in their brains.

The study on aging suggests that the regular practice of meditation may have neuroprotective effects and reduce the cognitive decline associated with normal aging.

If that is confirmed, I think that we have something else to add to our list of “things to do to reduce your risk of getting Alzheimer’s.”

Brain Training and the Paradox of Aging

For centuries, people in cultures throughout the world have believed that increasing age is associated with increasing wisdom. Not just knowledge and experience, but wisdom. Is this an old wives' tale, or is there something to it?

There is growing evidence that as we age our brains actually become stronger. Everyone missed it, because the emphasis was on memory, concentration and thinking speed, and those may all deteriorate with age. What changes is that as we age we become more efficient at making associations rather than thinking linearly. we also recruit regions of the brain that may have lain dormant for years. At the same time, different types of mental training, including meditation, can improve many aspects of our cognitive abilities, and may also enrich and even grow appropriate regions of the brain.

Some new data from a study being conducted at Wake Forest University Baptist Medical Center in North Carolina suggests that it is possible to use a fitness program for your brain that can improve thinking skills, attention and concentration as reliably as lifting weights can increase muscle strength.

Preliminary findings from the study, which used functional magnetic resonance imaging (fMRI) to record brain activity, were presented last week at the Organization for Human Brain Mapping conference in Chicago.

As we age, we do experience changes in how we perceive the information that our senses gather from the environment. As I mentioned older adults combine information from the different senses more readily than do younger adults. This is known as sensory integration, and the down side is that it can lead to difficulties in blocking out distracting sights and sounds while still maintaining focus on important information. You are probably familiar with the "Cocktail Party Phenomenon." You are in a loud room, but because someone is saying something interesting, you are able to block out uninteresting information. This technical term for this is cortricofugal inhibition. As we get older it gets more difficult to do the inhibiting.

The Brain Fitness in Older Adults (B-fit) study has been designed to establish whether eight hours of brain exercise can improve the ability of healthy older adults, ages 65 to 75 years, to filter out unwanted sights and sounds.

The B-fit study uses fMRI to visualize blood flow and brain activity to determine how attention training affects brain function. The training involves either a structured one-on-one mental work-out program or a group brain exercise program. During the one-on-one sessions, the volunteers were asked to ignore distracting information and tasks get harder as the eight-week training progresses. For the group sessions, participants learn new information relevant to healthy aging and are then tested on their ability to apply the new information.

All participants had an fMRI scan during a distraction task. They had to look for target words or numbers while ignoring distracting sounds. The scans showed brain activity in areas related to both sight and sound. Follow-up fMRIs showed that in the group receiving the one-on-one training, activity related to sight was increased, while activity related to sound was decreased. In addition, performance on the task was improved.

So the data do indeed suggest that attention training is a way to reduce older adults' susceptibility to distracting stimuli and therefore help improve concentration.

And what about wisdom?

I have written in Healing, Meaning and Purpose that "Wisdom is the integration of understanding:" making more new associations and drawing conclusions based on a new perspective is a gift of aging. The training enables us to make sense of and communicate our conclusions.

When it comes to the brain, use it or lose!

Successful Aging

One of the most promising changes in psychology is the ever-greater emphasis on what makes us healthy, rather than constantly looking at the things that make us sick. There is an important approach called Behavioral Activation (BA) Theory, which emphasizes environmental and behavioral factors as determinants of our overall well-being. According to the theory, reduced engagement in pleasurable activities may be an important precursor of reduced well-being. This makes good sense: it is estimated that as much as 90% of our higher cortical functions are designed for social interactions.

This is something that I wrote in Healing, Meaning and Purpose:

"Nothing in the Universe exists in isolation: We live in a Universe of relationships. It is inconceivable that anything can exist except in relationship to something else. The entire Universe is made up of integrated systems that function, develop and evolve together. A failure to construct and maintain healthy relationships can be a cause of much distress.

Several years ago I reported some interesting observations. At the time, I was doing a lot of research on diseases of blood vessels. I had developed a laboratory method for taking some of the cells that line blood vessels from volunteers and then growing them in a cell culture dish. We discovered that if we did not have enough cells in the dish, they would all die of “loneliness.” The exception is cancer cells, which in culture will grow on their own, like weeds."

As an example in a paper published in February in the Archives of General Psychiatry it was shown that lonely individuals may be twice as likely to develop the type of dementia linked to Alzheimer's disease in late life as those who are not lonely. The theory has been shown to predict psychiatric well-being in a number of populations, including the caregivers of people with Alzheimer’s disease, people with chronic pain, cancer patients and community-dwelling older people.

It is also known that psychiatric well-being, particularly emotional well-being, may play an important role in cardiovascular health. This may be due to an increase in the activity of the sympathetic nervous system that increases not only blood pressure, but also the levels of inflammatory mediators and coagulant factors in the blood.

In research from the University of California at La Jolla that was presented on Monday at the 2007 Annual Meeting of the American Psychiatric Association in San Diego, California, twenty two people with a mean age of 70 were studied, to see if there was a link between their behavioral activation, i.e. how satisfied they were with their leisure activities, their affective well-being and their blood pressure.

The findings were as expected: the less satisfied and engaged people were, the higher was their blood pressure.

This is only preliminary data, but it confirms something that we have said before: as we get older it is as important to stay socially engaged as it is to do mental exercise.

And if you known someone who is older and isolated, you might want to go and see them.

“The most terrible poverty is loneliness and the feeling of being unloved.”
--Mother Teresa of Calcutta (Albanian-born Indian Nun, Humanitarian and, in 1979, Winner of the Nobel Peace Prize, 1910-1997)

“What makes loneliness an anguish is not that I have no one to share my burden, but this: I have only my own burden to bear.”
--Dag Hammarskjöld (Swedish Statesman, Secretary-General of the United Nations from 1953-1961, and, in 1961, Winner of the Nobel Peace Prize, 1905-1961)

Attachment and Well-Being In the Elderly

Attachment theory is a psychological concept that was developed by John Bowlby in Britain and Harry Harlow in the United States in the late 1950s. The idea is that humans and many other animals have evolved an adaptive tendency to maintain proximity to an attachment figure.

Attachment is defined as an emotional bond that one person forms between himself or herself and another specific person. Originally the theory was developed to explain the relationship of a parent and child, but over tie it has become realized that attachments can occur throughout life, and if they become abnormal, they can lead to loneliness, isolation and psychopathology. There has recently been a resurgence of interest in attachment styles, and how they interact with emotional and behavioral expression during the development of dementia.

There was some interesting research presented today at the 2007 Annual Meeting of the American Psychiatric Association in San Diego, California. Investigators from Charlottesville, Virginia looked at 39 older patients (27 were women): 49% were aged between 65 and 74 and the remainder was over 74.

• 41% of women and 33% of the men said that their activities were limited by physical and/or emotional problems
• 41% of the women and 17% of the men endorsed at least two out of three indicators of depression
• When they examined their attachment styles, 28% were secure, 59% avoidant and 13% enmeshed
• An avoidant attachment pattern is more common among the elderly than it is among younger people
• Understanding attachment style could be very helpful in understanding how people react to their healthcare providers and their preferred coping styles

For anyone working or living with elderly people, attachment theory is well worth investigating. There is already some preliminary evidence that specific interventions may help older people with avoidant attachments.

Attachment theory is a psychological concept that was developed by John Bowlby in Britain and Harry Harlow in the United States in the late 1950s. The idea is that humans and many other animals have evolved an adaptive tendency to maintain proximity to an attachment figure.

Attachment is defined as an emotional bond that one person forms between himself or herself and another specific person. Originally the theory was developed to explain the relationship of a parent and child, but over tie it has become realized that attachments can occur throughout life, and if they become abnormal, they can lead to loneliness, isolation and psychopathology. There has recently been a resurgence of interest in attachment styles, and how they interact with emotional and behavioral expression during the development of dementia.

There was some interesting research presented today at the 2007 Annual Meeting of the American Psychiatric Association in San Diego, California. Investigators from Charlottesville, Virginia looked at 39 older patients (27 were women): 49% were aged between 65 and 74 and the remainder was over 74.

• 41% of women and 33% of the men said that their activities were limited by physical and/or emotional problems
• 41% of the women and 17% of the men endorsed at least two out of three indicators of depression
• When they examined their attachment styles, 28% were secure, 59% avoidant and 13% enmeshed
• An avoidant attachment pattern is more common among the elderly than it is among younger people
• Understanding attachment style could be very helpful in understanding how people react to their healthcare providers and their preferred coping styles

For anyone working or living with elderly people, attachment theory is well worth investigating. There is already some preliminary evidence that specific interventions may help older people with avoidant attachments.

Genes, Culture and Aging

The study of genetics is becoming ever more interesting. Not only have we gone well beyond the nature/nurture debate, but also there is more and more interest in genetic influences on culture and vice versa: the way in which culture impacts gene expression. It is also clear that our brains are amazingly plastic: nutrition, emotional environment, education and experience all impact brain development.

Now it appears that culture does indeed affect the brain.

Westerners and East Asian people process visual information differently: Westerners preferentially process objects, while Asians tend to pay more attention to contextual information. In studies of semantic organization, Asians associate pictures based on functional relationships, for instance grouping together a mother and her child based on maternal relationship. Westerners based their associations on physical features and categorical membership, such as grouping together a woman and a man because they are adults. These differences may be changing as young people in Asian cultures are becoming more westernized.

New research has found that the aging brain reflects cultural differences in the way that it processes visual information. This study “Age and culture modulate object processing and object-scene binding in the ventral visual area” is published this month in the journal Cognitive, Affective & Behavioral Neuroscience. This paper (which can be downloaded here) and another published by the same group in 2006 are the first to demonstrate that culture can alter the brain's perceptive mechanisms.

The research is the result of a collaboration between Denise Park’s group from the University of Illinois and Michael W. Chee, of the Cognitive Neuroscience Laboratory, SingHealth, in Singapore. The researchers conducted an array of cognitive tests on study subjects at their facilities in the U.S. and Singapore, and used identical functional Magnetic Resonance Imaging (fMRI) scanners at both sites. Their analysis involved 37 young and old East Asians, and 38 young and old Westerners. They found significant cultural differences in how the older adults' brains responded to visual stimuli.

As Professor Park said,

"These are the first studies to show that culture is sculpting the brain. The effect is seen not so much in structural changes, but at the level of perception."

We have known for decades that East Asians and Westerners process visual information differently. A paper in 1972 reported that East Asians are more likely to pay attention to the context and relationships in a picture than are Westerners, who more often notice physical features or groupings of similar subjects.

More recent research, which analyzed the eye movements of East Asians and Westerners viewing identical images, found that Westerners were more attentive to central, or dominant, objects, while East Asians paid more attention to the background, or scene.

Last year the team reported differing patterns of neural activation in the brains of East Asians and Americans shown identical pictures. The Americans showed more activity in brain regions associated with object processing than the East Asians, whose brains showed more activity in areas involved in processing background information.

The new study takes this work further, comparing neural responses to visual stimuli in young and old adults in both cultures. These are some of the pictures they used in the experimenets:

The researchers found that all four groups - young and old East Asians; young and old Americans - processed background information in part of the brain called the parahippocampal gyrus: a region that is vital to memory encoding and retrieval. As expected, older adults in both cultures had less ability to use “binding mechanisms” - the ability to connect a particular object to its background - in the hippocampus. The older people also had diminished object processing in the lateral occipital cortex.

The most striking finding was that the “object areas” of the brains of older East Asian subjects responded much more weakly to novel stimuli than did those same brain regions in the older Americans. For the older East Asians, a lifetime of attention to the backgrounds, or context, of pictures eventually showed up as a diminished response in the part of the brain that keeps track of foreground objects.

One of the best ways of keeping the brain healthy is with cognitive cross training: doing things like crossword puzzles, but also doing things that exercise other cognitive muscles, like playing the piano. This research would suggest that the exact strategies that we should use will be different in native-born Asian and western-born people. Something to factor in the next time that we get some advice about how to keep the brain young for as long as possible.

Blueberries and Colon Cancer

I have been delighted to see how many people have read and downloaded my Twelve Tips to Reduce Your Risk of Colon Cancer.

There is some new research that was just presented at the shows tha there is a compound in blueberries called pterostilbene that may help protect against the development of colon cancer.

Researchers from Rutgers University and the US Department of Agriculture presented their findings at the meeting of the American Chemical Society in Chicago.

Pterostilbene is a natural antioxidant that mops up free radicals that may, in excess, trigger the growth of some cancers. Similar antioxidants have already been identified in grapes and red wine. Work in mice suggests that pterostilbene may also lower cholesterol levels. The compound also reduced inflammation and the rate of cell division in the bowel both of which are considered to be cancer risk factors.

Pterostilbene is also found in cranberries, sparkleberries, lingonberries and grapes.

It is an extremely good idea to add blueberries to your diet. Do not overdo it! I worry when people extol the virtues of some super-food or super-drink that is supposed to abolish all of your free radicals. Despite the claims of at least one medical correspondent on Fox New, there is usually no evidence that they do so. And in any case, you do not want to abolish all your free radicals: they are key cancer killers.

You want to balance and modulate the free radicals in your body, and blueberries, together with four other portions of fruit and vegetables a day are one excellent way of doing so.

Aging and Exercise

It is a common observation that it becomes more difficult to do a lot of exercise as we get older, and the biceps no longer bulge quite as much after an hour in the gym. We have to exercise harder to get the same results.

Metabolism slows down as well, and for years it has been assumed that those events are linked: we slow our metabolism and find exercise harder because we gradually lose muscle mass.

But new research shows that it isn’t quite so simple, and the results should encourage any of us over forty to stay in the gym.

A new study published in the journal Cell Metabolism will likely help our understanding of that difficulty, as well as unlocking another of the secrets of type 2 diabetes.

As we become older, we hide more fat in our muscles and livers, and this fat has been linked to the age-related rise in insulin resistance that may go on to cause type 2 diabetes and hypertension.

A research team from the Howard Hughes Medical Institute based at Yale University School of Medicine compared the skeletal muscle of rats aged three-month-old and two-year-olds.

They found that an enzyme called AMP-activated protein kinase (AMPK) slowed down its activity in the older animals. AMPK's role in skeletal muscle is to stimulate the body to burn off fat and to provide fuel for the cells. It does this by producing mitochondria – the power packs of the cell. So AMPK activity in our skeletal muscle does at least three things: it stimulates glucose uptake, increases fat oxidation and promotes the production of new mitochondria.

It has been known for some time that the skeletal muscles of marathon runners have a much greater mitochondrial content and a greater capacity to burn fat. This is probably linked to high levels of AMPK activity.

The animals were exposed to a chemicals that produce that produce acute or chronic stimulation of AMPK. They were also exercised and some were fed more food, each of which should stimulate the production of new mitochondria.

The researchers found that the older rats had lower AMPK activity than the younger animals. In addition, the muscle of young rats who did more exercise had double the normal AMPK activity while in older rats this effect was severely blunted.

The message is this: as we age it is not muscle mass but enzyme activity that falls first. We have to work harder when trying to maintain the same benefits from exercise as we did when we were young.

We know that loss of skeletal muscle mass and function as we age is a major problem that has a significant effect on quality of life of older people. If this study is confirmed in humans it would have enormous implications. In the older rats, the AMPK activity was almost gone, implying that no amount of exercise would bring those muscles back. But it would be good to know if we can work out some other methods for bringing those enzymes back to life.

Although the paper doesn’t mention it, there is also some evidence that AMPK activity may be important in controlling feeding behavior in the hypothalamus at the base of the brain and the “stress hormone” norepinephrine plays a critical role in the way in which exercise stimulates AMPK. As we get older we usually find that our tempers are less fiery and part of the reason for that is that we produce less norepinephrine.

Start exercising early in life, and never get out of the habit. For if you do, you might lose that AMPK activity forever.

“Wholesome physical exercise reconstitutes energy, stemming the aging process, making the body light and firm, while safeguarding against fatigue and inducing cheerfulness.”
--Sushruta Samhita (Indian Surgeon who wrote the book the Sushruta Samhita, c. 6th Century B.C.E.)

“Exercise is the chief source of improvement in our faculties.”
--Hugh Blair (Scottish Presbyterian Minister and Writer, 1718-1800)

“It is exercise alone that supports the spirits, and keeps the mind in vigor.”
Marcus Tullius Cicero (Roman Political Figure and Orator, c.106-43 B.C.E.)

A Major Breakthrough in Neurogenesis Research

I have written a lot about adult neurogenesis, because it is so incredibly important.

When most of us were in school were taught that the brain is a static structure. That you are born with a certain number of neurons, that constitutes your neural “stash.” And after the age of five you would lose a hundred thousand neurons a day, and if you drank too many martinis it would be two hundred thousand a day. “Facts” and figures repeated from one textbook to another for fifty years. And quite wrong.

Ten years ago it was discovered that there are neural stem cells in the hippocampi of adult rodents. A study published in 1998 provided some evidence that neurogenesis takes place in the adult human hippocampus, but the idea that neurogenesis takes place in adult humans has remained contentious.

Now, an advance online publication on the website of the journal Science provides evidence that neurogenesis may also occur in the olfactory bulb of the human brain.

The whole article, including the pictures is available here. The picture at the top of this article shows new cells appearing in the olfactor bulb.

The investigators examined the rostral migratory stream (RMS) which is the main pathway by which newly born cells from the subventricular zone (SVZ) reach the olfactory bulb in rodents. The researchers discovered that there is a human RMS containing neuroblasts, a.k.a. neural stem cells.

(This is a rat olfactory bulb)

Maurice Curtis and his colleagues examined the brains of cancer patients who had recently died, after having been previously injected with bromodeoxyuridine (BrdU), a chemical that is incorporated into newly synthesized DNA. Cell biologists and oncologists have used the method for years to visualize and monitor the growth of tumors. The researchers found BrdU-positive cells in the olfactory bulbs of the patients’ brains, indicating that they contained newly-generated neurons.

The team then used antibody staining to show that the neuroblasts begin to differentiate into olfactory neurons while migrating through the rostral migratory stream. Upon arriving at the bulb, the cells continued to differentiate, forming mature olfactory neurons.

The patients whose brains were examined were between 38-70 years of age, so the findings show that neurogenesis may occur throughout the duration of the human lifespan. The function of these newly generated cells is unclear, but they may be involved in recognizing and remembering new smells in the later years of life.

The researchers also have preliminary unpublished data that the stem cells not only migrate to the olfactory bulb, but also leave the RMS and migrate into the basal ganglia and cerebral cortex. This is significant, because parts of the basal ganglia degenerate in movement disorders such as Parkinson’s Disease, and specific regions of the cortex degenerate in Alzheimer’s. The possibility that stem cells enter these regions from the RMS could therefore provide a means for developing new treatments for neurodegenerative diseases.

So although at the moment new neurons are only known to be created in a small number of ancient structures in the brain, but that may well change, since the cells are marching over there from regions around the ventricles. After all, why would Nature, the Universe or God have left neural stem cells sitting there unless it was for a good reason? And if adult neurogenesis can be demonstrated in other parts of the brain, then what? An end to the stem cell debates? If the stem cells are already present in the brain, the effort can be directed toward activating and directing them. Could we continue generating new neurons to stave off the dementing illnesses, or is that just science fiction?

The answer is that science fiction is fast becoming science fact. This research will need to be replicated, but I know of several other labs that have already accumulated some similar data to this new paper in Science.

Dexterity and Strategy

I am a great believer in trying to do new things to stimulate latent abilities in the brain: there is more and more evidence about how valuable that can be.

Here is a very simple little game that can provide you with an excellent neurological work out.

Do not try it for more than a minute or two, or you might get repetitive strain injury or a psychological meltdown!

Juices, Cardiovascular Disease and Cancer

There was an important study that came out a few months ago in the International Journal of Food Science and Nutrition.

Investigators from Dundee in Scotland decided to look at the health benefits of fresh fruit juice. While it is widely accepted that fruit and vegetables lower the risk of some cancers and of most cardiovascular diseases, the role of pure fruit and vegetable juices has never been clear. In fact many textbooks have said that 100 percent juices play a less significant role in reducing risk for both cancer and cardiovascular disease than whole fruits and vegetables since they contain less fiber, and it had been assumed that it was the fiber that was the key to their value.

The researchers analyzed a variety of studies that looked at risk reduction attributed to the effects of both fiber and antioxidants. They found that the positive impact offered by fruits and vegetables is derived not from just the fiber but also from antioxidants which are present in both juice and the whole fruit and vegetables. Juices are comparable in their ability to reduce cancer and cardiovascular risk compared to their whole fruit/vegetable counterparts.

This research  goes a long way in demonstrating that fruit and vegetable juices may play an important role in reducing the risk of various diseases.

A study published in the American Journal of Medicine in September found that consuming a variety of 100 percent fruit and vegetable juices was associated with a reduced risk for Alzheimer's disease. Japanese American individuals who drank three or more servings of fruit and vegetable juices per week had a 76 percent lower risk of developing Alzheimer's disease than those who drank juice less than once per week. That finding seemed robust, even taking into account other potential variables. So I think that we may be able to add juices to our strategies for reducing the risk of developing Alzheimer's disease as we get older.

There is another point of importance. Some of the fad diets claim that fruit juices should be avoided at all costs, since they can cause the release of insulin, and insulin is bad. Those proclamations have usually come from people with a limited background in biochemistry or metabolism. The research shows that they were not correct. The key is balance, and as part of a comprehensive nutritional approach, juicing can be very helpful.

And a final point: careful use of juices has long been one of the "secret" components of our system of weight management.

“Drinking freshly made juices and eating enough whole foods to provide adequate fiber is a sensible approach to a healthful diet.”
--Jay Kordich (American Health Expert, Author and Lecturer, 1921-)

“If people would only stop putting into their bodies the things that are creating their physical problems, and eat a predominantly raw vegetarian diet, along with raw vegetable juices, almost all physical problems would soon disappear from the face of the earth!”
--Reverend George M. Malkmus
 (American Minister and Originator of the Hallelujah Diet, 1934-)

Cognitive Brain Health Test

One of the blogs that never fails to provide me with some food for thought is Zack Lynch's Brain Waves.

He has just alerted his readers to a very interesting resource.

The Brain Resource Company launched a free, confidential, 40-minute cognitive brain test in partnership with the Alliance for Aging Research. The company is offering the test at no cost until May 14, 2007.

When you first click on the link for the test, you are taken to a page on Brain Health with a great many links.

I am extremely familiar with the literature on the brain, aging and cognition. So on your behalf, I passed a critical eye over the material. I was really pleased with it. I have one or two very minor quibbles, and one or two of the links are not working yet, but overall the information is excellent and above all reliable.

One thing about doing the test is that it needs for you to be using Windows. So we Macintosh users are left out in the cold. But the test is well worth doing, so if you are a Macintosh user, you might want to see if you can borrow a Windows machine for an hour.

“Most people would sooner die than think; in fact they do so.”
--Bertrand Russell (Welsh Mathematician, Philosopher, Pacifist and, in 1950, Winner of the Nobel Prize in Literature, 1872-1970)

“The longer I live, the more beautiful life is.”
--Frank Lloyd Wright (American Architect, 1867-1959)

Spicy Foods as Cancer Killers

Several news services have picked up a very important piece of research in the February 16th issue of the journal Biochemical and Biophysical Research Communications.

In a nutshell, they have shown that capsaicin, an ingredient of jalapeno peppers, triggers cancer cell death by attacking mitochondria, the energy producing organelles in the cell. Some of the reports were a little confused and confusing and also missed out some critical pieces.

So first, a bit of revision, this is a graphical representation of what a mitochondrion looks like:

The mitochondrion is the primary producer of energy in the cell, converting molecules derived from food or stores into adenosine triphosphate (ATP) and several other less important molecules. ATP is the energy "currency" throughout the body. In recent years we have discovered that there are a number of diseases that are a result of faulty mitochondrial metabolism.

One of the biggest problems about most forms of chemotherapy for cancer is that the treatments often damage normal cells as well as the malignant ones. Therefore a great deal of research has aimed at identifying differences between normal and malignant cells.

Over the last ten years, increasing evidence has shown that mitochondrial dysfunction is a key feature of many types of cancer as well as part of normal aging. This has lead to the idea that we might have a new therapeutic target if cancer cell mitochondria are different from those in normal cells.

This new study showed that the family of molecules to which capsaicin belongs, the vanilloids, bind to proteins in the cancer cell mitochondria to trigger apoptosis - programmed cell death - without harming surrounding healthy cells. Capsaicin was tested on cultures of human lung and pancreatic cancer cells.

As the lead researcher Timothy Bates has said, "We believe that we have in effect discovered a fundamental 'Achilles heel' for all cancers."

This is extraordinarily interesting, not least because capsaicin is already in use for the topical treatment of peripheral neuropathy and some inflammatory conditions of the skin including psoriasis. The amount of capsaicin used in the experiments was similar to amounts that could probably be ingested safely. So now the next step if to see whether these observations can be translated into a viable treatment option for cancer, and if so, which types.

What the research does not say is that eating a lot of spicy food will help prevent or treat cancer.

The reports that I have seen have failed to mention that one of the reasons for doing this research was that  some spices have been used in traditional Chinese and Indian medicine for many centuries for the treatment of several conditions, and some of the investigators are engaged in the Nottingham UK–China Collaboration on Complementary and Alternative Medicine.

How many more treasures are waiting for us in the archives of traditional medicine?

And how many have already been lost as plant and animal species become extinct?

Healthy Aging

I have talked about the small number of simple steps that can dramatically reduce your risk of getting congnitive decline as your get older and some new evidence to show the benefits of non-drug treatments for dementia. I am pleased to say that my conclusions have just been supported by an editorial in the Journal of the American Medical Association.

I would like to let you know about another great resource: the International Council on Active Aging (ICAA) which has produced a great package of action items that are all rooted in good quality scientific research. The list is very similar to the ones that I have created for you here, and are very precise.

1. Invest in good shoes and socks
2. Play games
3. Walk
4. Increases your physical activity
5. Do exercises to improve your balance
6. Get regular eye checks, not only for corrective lenses, but to be checked for early evidence of diabetes or high blood pressure
7. Seek out friends family and neighbors
8. Modify your diet toward a "Mediterranean" one
9. Laugh
10. Get enought sleep

Whatever your age, I urge you to spend a few minutes working on a simple plan that will fit your schedule: your mind and body, family and friends will thank you forever.

Brain Gain

We have previously discussed how a relatively small number of strategies can dramatically reduce your risk of cognitive decline as you get older.

Our recommendations are firmly buttressed by a most important article available for free download at the website of the Journal of the American Medical Association.

We already knew that cognitive training can improve cognitive abilities in older adults but nobody had established the effects of cognitive training on everyday function.

Sherry Willis of Pennsylvania State University led a team of scientists that followed a group of 2,832 adults, aged 65 and older -mean age 73.6 years - who were still living independently between 1998 and 2004. The seniors came from all walks of life, races, and parts of the country, including Birmingham, Alabama; Detroit, Michigan; Boston, Massachusetts and three other major cities. They all had one thing in common when the study commenced: they had no signs of cognitive impairment.

The researchers divided them into four groups of roughly 700 each: three groups that would receive training in either memory (verbal episodic memory), inductive reasoning or speed of processing (visual search and identification) with 4-session booster training at 11 and 35 months after training, and one that would serve as a control.

The memory training program consisted of mnemonic strategies for remembering word lists or texts, such as associating various words, visualizing them or organizing them in specific ways. Reasoning training taught the participants how to spot the pattern in a series, such as "a c e g i... ." The researchers boosted the subjects' processing speed via practice, practice, practice in identifying an object on a screen after increasingly short exposures.

Over the course of the next five years the researchers asked participants to appraise their skills and to report whether the training had helped with everyday tasks. They also independently evaluated the subjects' skills in things like finding items in a medicine cabinet. After training, 87 percent of the speed trainees, 74 percent of the reason trainees and 26 percent of memory trainees showed immediate improvement. That advantage over their untrained peers persisted over the next five years.

The training seemed to largely offset the cognitive decline suffered by nearly all of the controls as the years wore on. By the fifth year, significant skill gaps had opened between the people who had done the training  and their untrained peers.

It is not enough to continue to do the crossword or sudoku puzzles. The brain must be continually stretched and challenged. It seems that to drive this effect, you have to practice things that you don't like or things you don't regularly practice.

Many of us have spent years working on new training strategies, and this research shows just how valuable cognitive training can be for all of us.

Genes, Environment and the Brain

We recently looked at the worrying suggestion that environmental toxins could, in susceptible individuals, be contributing to the apparent increase in autism over the last three decades.

There is increasing evidence that there are complex genetic and environmental interactions that contribute to abnormal aging and neurodegenerative disorders like Alzheimer’s, Parkinson’s and Huntington’s diseases.

A new study from Duke University Medical Center in Durham, North Carolina, has done more to dissect this interaction. They collected information on 1136 consecutive patients who presented to the Joseph and Kathleen Bryan Alzheimer Disease Research Center. They showed possible significant contributions of toxic environmental and occupational exposures to pathological aging in 21% of the patients, and interactions of these exposures with common genetic polymorphisms that affect cell injury and inflammation. They found a series of genes that could partially account for differences in the type of cognitive problems that people experience, the age at which they developed them as well as the rate of progression.

The researchers targeted three genes in particular - apolipoprotein E, alpha-1-antitrypsin and the hemochromatosis gene. All three are expressed in the liver and in macrophages: cells that play a critical role in immune responses, inflammation and the body’s response to stress and infections. The first two genes are particularly involved in the metabolism of lipids and the third in the balance of iron and trace minerals. This ties in with another observation. Many chronic illnesses are associated with anemia. It is now thought that this also is a defensive reaction. Not to chronic illness, but to the problem that was far more common during evolution, and that was infection. The liver pulls iron out of the circulation so that bacteria cannot use it for their own growth. This is one of a number of adaptive responses that I discuss in the book and CD series, Healing, Meaning and Purpose.

But it was also clear form this new study that genes were not the only factor. I have spoken before about the small number of strategies that can dramatically reduce our risk of developing Alzheimer’s disease. The authors of this study agree about the importance of factoring in environmental factors including, alcohol use, nutritional deficiencies and sleep and mood disorders, all of which can have an impact on cognition.

This study is yet another step toward clarifying the role of genes, inflammation and cell injury in the development of degenerative changes in the brain.

While pharmacologists can use this information to help devise new ways to protect your brain, you can use it immediately. There is a range of behavioral and dietary strategies that can reduce the burden of inflammation in the body. I shall write about some of them in articles and an eBook in the near future.

We do not know whether these strategies can reduce the risk of Alzheimer’s and Parkinson’s diseases, but there are some intriguing suggestions that they can.

Memory Molecules

There are still a great many mysteries about memory:

• The molecules in neurons are constantly changing, as are many of the connections between cells. So how can memory be maintained for a lifetime in an environment that is in a constant state of flux?
• Why is it that you can remove large regions of the brain yet memories are not lost? Even in the late stages of Alzheimer's disease, some long-term memories are maintained even when much of the brain is taken over by plaques and tangles.
• How much memory is there outside the brain and in the body?
• Is some memory maintained not in the brain itself but in fields associated with the body?

Gradually some questions are being answered not just by technology, but by asking new questions and bringing new types of expertise to bear on these problems.

A very interesting new study was published last week in the Journal of Neuroscience. The paper was not by neurologists, but by two mathematicians from the Brain Institute at the University of Utah. Their research suggests that memories are held in our brains because certain proteins serve as anchors, holding other proteins in place to strengthen the connections between nerve cells known as synapses. The anchors keep proteins in place, and these proteins in turn determine how strong a synapse is. And the strength of the synapse is a key to forming and retaining memories.

Synapses function by electrical activity in a neuron releasing a chemical neurotransmitter that affects another neuron or an organ.

One of the primary neurotransmitters involved in learning and memory is called glutamate, that binds to a number of receptors. But the most important for memory are the "AMPA receptors" that are embedded in the receiving ends of neurons. The AMPA receptors are held in place by special scaffolding molecules.

The mathematicians were able to make several predictions about the way in which AMPA receptors stay in place and how repeatedly learning something strengthens the connections between neurons.

The key to learning and remembering is anchoring AMPA receptors on our neurons.

I went into the technical side a bit, because this finding may help us get closer to understanding what goes wrong in Alzheimer's disease.

It also ties in with some other research out this week in the journal Neuron. A team from the Univesity of Oxford has been trying to work out why adults may find learning more difficult than children. The young learn things more easily, but older brains stiore information more efficiently. They also focused on synapses, and  seem to have found the mechanisms involved.

Young brains have many "silent" synapses that don't do anything unless called upon to learn something. Older brains have to reuse synapses that have already been used, boosting the strength of connections with increased amounts of neurotransmitters.

So as we get older, our brains adopt different strategies for learning new material, and we should get ever better at organizing and integrating information.

That also fits with the strategies that we have used for improving people's ability to learn and remember. We use connections as in Mind mapping, multiple sensory associations inclusing music, color and smells, and a sophisticated method for asking constant questions to see if new information fits with material that we have already asimilated.

À Votre Santé!

I am a wine buff. Several years ago I did a one year training with the Wine and Spirit Education Trust which turned me from a dilettante to someone who knew how to understand the subtlety of wines from one end of a vineyard or another. Oh yes, and how to get very good wine for not many $$.

I also learned a whole range of other new skills. Ever since then I've been interested in the health consequences of drinking wine. Of course, too much of a good thing isn't. But there has been so much evidence that certain types of wine, when used in moderation, can do wonderful things for your health.

This week has seen the publications of a paper in the journal Nature, that has been described by Steve Bloom from the Imperial College Faculty of Medicine like this: "It could be the breakthrough of the year, with massive possibilities for treating human beings."

Steve is not given to hyerbole, so what has got him so passionate?

The answer is that a chemical found in dark grapes and in red wine called resveratrol, that could make guilt-free gluttony a reality.

Why is this?

Previous research has revealed the substance has anti-ageing effects in some organisms, extending the lifespan of yeast by 60%, worms and flies by 30%, and fish by about 60%.

It has also been suggested the reported health benefits of red wine may also be due to resveratrol.

When given to mice, it countered some effects of a high-calorie diet, with 60% of the calories coming from fat, improving their health and increasing their life-span. The mice showed decreased glucose levels, healthier hearts and liver tissue, and better motor function compared with the mice on the same diet but without the supplement.The chemical could not reverse all consequences of overeating - the mice did not lose any weight.

The researchers also discovered that the chemical was extending the mice's life-span. The scientists estimated resveratrol reduced the risk of death in the mice by about 31%. After six months, resveratrol essentially prevented most of the negative effects of the high calorie diet in mice.

The exact mechanism of the chemical is not yet known, but the researchers believe it may be activating a gene called SIRT1, which is linked to a family of proteins thought to be involved with longevity.

This is not yet an invitation to enjoy limitless quatities of grapes or wine: a glass of red wine has only 0.3% of the relative resveratrol dose given to the gluttonous mice.

BTW, you may be interested to know that Nature is now providing an excellent podcast based on papers in this week's edition.

DHEA: Hype, Hope and Disappointment

Dehydroepiandrosterone (DHEA) is a hormone that has attracted a lot of attention. It’s launched hundreds of websites, product lines and a few books and magazine articles. So what’s all the fuss about, and should we all be chomping down on DHEA tablets?

DHEA is manufactured at several sites in the body, but by far the most important is in one of the outer layers of the adrenal gland. Like all the steroid hormones it is made from cholesterol. It has various protective effects in the body, regulates some enzyme systems, can be converted to estrogen and under certain circumstances to testosterone. It has very weak androgen (male hormone) activity.

In cell culture it has a lot of other actions too, but it is always difficult to jump from effects seen using large doses in isolated cells, to giving advice on what supplements people should be taking.

There has been a lot of talk about the possibility that some people may, as a result of stress or toxins, suffer from exhaustion of the adrenal glands. There is a great long list of symptoms that may be caused by this so-called adrenal fatigue, deficiency or insufficiency: the terms are often – and incorrectly – used interchangeably. And therein lies the problem. It is such a long list that it is non-specific. It’s always a bit of a worry when someone tells me that dozens of different symptoms are all caused by one single biochemical problem. That just isn’t the way that the human body works.

I have seen and treated countless people with a condition known as Addison’s disease: true chronic adrenal insufficiency. It can be a very serious illness and it is quite different from the “adrenal fatigue” that people talk about in some popular books. People with chronic fatigue syndrome do have lower levels of activity in what is known as the hypothalamic-pituitary-adrenal axis, but it is not because the adrenal glands are not working properly, but because the hypothalamus in the brain is not doing it’s job properly. There’s also no proven link between “burnout” and adrenal function.

During my years as an endocrinologist and holistic physician, I’ve spent a great deal of time looking for adrenal fatigue in sick people and I’ve never found it. I’ve done all the tests recommended by proponents of adrenal fatigue and adrenal insufficiency and when we’ve done the tests properly, we’ve drawn a blank. There are a great many parallels between the adrenal insufficiency story, and the old - and discredited - myth about people becoming unwell because of a thyroid deficiency that cannot be picked up on standard thyroid function tests.

So can DHEA do you any good? Or can it be harmful? What exactly is the evidence?

1. There is a comprehensive study, called The Dehydroepiandrosterone And WellNess (DAWN) study that should give us some solid answers as to the risks and benefits of DHEA. I shall post details of the findings as they become available. But some things we know already:
2. DHEA has been touted as an anti-aging supplement. But in a two-year prospective study done in older people attending the Mayo Clinic in Rochester, Minnesota, neither DHEA nor low-dose testosterone replacement had physiologically relevant beneficial effects on body composition, physical performance, insulin sensitivity, or quality of life. Perhaps the people in the study didn’t get enough DHEA, but it doesn’t look that way. Instead it seems that just giving the supplement doesn’t seem to do very much. But there is increasing evidence that 50-100mg of DHEA each day will improve muscle strength and muscle mass in older people who are doing strength training. Once again, it does nothing in people who are not exercising. Sorry!
3. According to the results of a small placebo-controlled, randomized trial published in the Archives of General Psychiatry, DHEA can be effective for midlife-onset minor and major depression. The study was conducted the National Institute of Mental Health Midlife Outpatient Clinic. In the trial, 23 men and 23 women aged 45 to 65 years with midlife-onset major or minor depression were randomized to six weeks of DHEA therapy, 90 mg/day, for three weeks and 450 mg/day for three weeks or to six weeks of placebo followed by six weeks of the other treatment. The subjects did not receive any other antidepressant medications during the study. Both of the doses of DHEA helped improve depression: there was no advantage in going to a higher dose, and there was no difference in the treatment response of men and women. The trouble with this study was not just the small size and the short duration, but the DHEA was not compared against a standard antidepressant. So we are still in the dark as to how effective it really is. It’s nice that it’s better than placebo, but this is just the first step in a larger research program.
4. A study from Taiwan indicated that people with higher levels of DHEA sulfate had a lower overall mortality over a three-year period. That is interesting, but absolutely does NOT mean that artificially increasing our levels of DHEA with supplements will make us live forever: we don’t yet have that kind of magic bullet.
5. In mice, quite large amounts of DHEA have the effect of slightly reducing the normal increase in stiffness of the left ventricle that can happen as animals get older. We have no idea whether something similar might help in humans, and the amounts of DHEA involved may rule it out as a viable treatment in people.
6. 50mg/day improves subjective wellness in people who have no active pituitary gland. A rare condition, and we cannot use this evidence to advise healthy people about what to take.
7. Because DHEA is converted into estrogen and/or testosterone, it may have the potential to exacerbate or initiate hormone-responsive tumors. The evidence is not strong one way or the other, but it remains a worry. I don’t think that anyone recommends DHEA to people who have a personal or family history of breast or prostate cancer.

There is a BIG literature on DHEA. But my current conclusions from all this?

1. 50-100mg of DHEA is probably worth trying if you are over 50 years of age and doing regular exercise.
2. It may help a bit with mild depression.
3. It should not be used in people with a personal or family history of breast, prostate or any other type of hormone-sensitive cancer.

Aging, Skin and Cancer

There’s a very interesting paper in this month’s issue of the journal Developmental Cell, based on research conducted at the Oregon Health & Science University in Portland, Baylor College of Medicine in Houston and Leiden in the Netherlands.

The investigators have found a pathway through which a gene's over-expression causes stem cells in the skin to switch from creating hair follicles to creating sebaceous glands. This discovery may not only provide us with new ways of treating hair loss and oily skin, but it may help us to prevent and treat some cancers.

Skin cells turn over very quickly: just think how fast a graze gets covered over. Epidermal stem cells give rise to the outer layer of the skin that serves as a barrier for the body, as well as generating the follicles that produce hairs and sebaceous glands. These glands produce oils to lubricate the skin. In aged skin, a protein called Smad7 is overproduced, which triggers hair loss and sebaceous gland growth.

This is the first study definitively to link Smad7 over-expression and the pathological changes that occur in aged skin.

Here’s the twist: Smad7 shuts down signaling of another group of genes called Wnt. It binds to a Wnt signaling protein known as Beta-catenin and degrades it with an enzyme called Smurf2. (I don’t known why they decided to call it’s call it Smurf: it looks like ponderous chemical humor to me!) Wnt signaling is critical for organ development, but if Wnt signaling is too active, it also causes cancer.

Enhanced Beta-catenin signaling contributes to many types of cancer, including colon, lung and brain. Perhaps inducing over-expression of Smad7 or delivery of Smad7 directly to tumor cells would provide a therapeutic approach because of the boost in Beta-catenin degradation.

And finally, impaired Beta-catenin signaling contributes to neurodegeneration, such as that found in Alzheimer's and Parkinson’s diseases, retinal degeneration, some bone density defects and aging. For these diseases, blocking Smad7-mediated Beta-catenin degradation may offer a therapeutic approach.

Blueberries

One of the principles of integrated medicine is that anything that’s good for you should have more than one benefit. So omega-3 fatty acids may help with cardiovascular health, mood, memory, attention deficit disorder, as well as the health of skin and bones.

Another one is the blueberry. I’ve been sufficiently impressed by the data on the health benefits of blueberries to have been a regular grower and consumer for years. They contain a number of potentially healthful compounds including polyphenols and anthocyanins, which can help modulate and balance the free radical systems of the body. Remember what I said recently about the value of keeping some free radicals in the body? The last thing that we want to do is to be rid of all of them!

There is reasonably good evidence that regularly eating blueberries can support cardiovascular health and there have been suggestions that they may reduce the risk and aggression of cancers of the prostate and colon.

There is also some evidence in animals that some of the components of blueberries may reduce inflammation and the effects of strokes – interruptions to the blood flow in the brain.

As a consumer, I’ve been carefully watching the growing evidence indicating that blueberries – or some of their constituents may have effects on animal cognition, brain aging and the normal neuroprotective mechanisms in the hippocampal region of the brain.

We do not yet have proof that these same effects occur in humans, and there are always three questions when we look at nutritional data:

1. Can we extrapolate from the animal to humans? Mice are not men
2. Are the amounts of blueberries or blueberry extracts even close to what humans could consume without spending all day eating, or getting a terribly upset intestine? There have been countless reports of the benefits of supplements that had to be taken in the most enormous doses to do any good. I’ve mentioned before the problem of L-arginine, which is sold as a “Natural Viagra.” Except that you need to take around nine grams for it to do much good, and most supplements contain less than a tenth of that. Regular readers will also remember my report concerning an article on coffee and sex. It was said that coffee would raise a woman’s libido. And indeed it does, if she drinks at least ten large cups of coffee at once. And coffee is a marvelous diuretic.
3. When extracts are used, are we sure that we are getting the correct ingredient of the fruit? Many beneficial fruits contain just the right combination of nutrients to help us, so each can be taken in a small dosage or concentration. As with so much in integrated medicine, combinations are key. Take out one extract of a fruit, and you may lose the clinical effect that you wanted.

All that being said, the evidence is becoming progressively more interesting, and there is enough suggestive evidence for me to keep packing away the blueberries.

And just to show that I leave no stone unturned when checking the literature on your behalf, I rejoiced to learn that supplementing the diet of Arctic char with various supplements - including blueberries – improved the quality of his, ahem, semen. I do not know how this information will help any of us yet. Neither do I really know why a fish would want to eat blueberries or any of the other supplements that they were tried on. Though I'm sure that people have often asked similar off the wall questions about some of my research....

Free Radicals, Aging and Small Hairless Creatures

I’m accused of many things.

Apart from the oft-repeated falsehood that I was the inspiration for Hugh Laurie’s brilliant characterization of the cranky Dr. Gregory House (I definitely was not!), I have been accused of having a fixation with mole rats. Well, that one is partly true: they are fascinating little creatures.

But let me start at the beginning. Over the last three decades, free radicals have entered the national vocabulary. In the 1983 James Bond movie, Never Say Never Again Edward Fox orders Sean Connery to enroll in a health clinic in order to "eliminate all those free radicals."

Free radicals are found in nature: they can be derived from combustion and some other chemical reactions and they are generated in the atmosphere by the action of ultraviolet radiation with chlorofluorocarbons. But most found in the human body don’t come from the environment: they are generated by biological processes. The majority are extremely short lived, but a few special types can hang around for hours.

An excess of free radicals has been linked to an array of illnesses, including:
Some cancers
Diabetic vascular disease
Parkinson’s disease
Schizophrenia
Alzheimer’s disease
Emphysema
Age-related changes in the skin
Macular degeneration

This list just names a few: many other illnesses have been laid at the door of free radicals. You will often see people talking about “oxidative stress,” to describe the damage done by an excess of free radicals. There is a theory that normal aging may be a result of the gradual increase in the production of free radicals in the body

There is something to all this: I did some research on the role of free radicals in diabetic vascular disease in the 1980s, and made some interesting discoveries. It has recently been shown that an excess of free radicals in the wrong place can play a part in generating insulin resistance.

The trouble - as with so many apparently simple ideas - is that many of the popular concepts about free radicals are over-stated or even wrong.

We first have to ask ourselves, “If free radicals are so bad, then why does the body produce them at all?”

The answer is that free radicals play a crucial role in a number of important biological processes, including the killing of bacteria by a group of white cells known as granulocytes. They are also thought to be key cancer killers and prime mediators of normal communication between cells.

Yet they have been pilloried: thought to be the key to so many illnesses when, in fact, they are intimately involved in normal biological processes: if you had no free radicals you would probably die quickly and unpleasantly. We know that because there is a group of rare, fatal illnesses in which children cannot generate free radicals.

Rather than focusing on ways to eliminate free radicals, we should be dealing with ways to balance them.

Our bodies are loaded with sets of enzymes whose task is to mop up excessive numbers of free radicals. The most important of these are superoxide dismutase, glutathione peroxidase, glutathione reductase and catalase.

When you see an advert or article extolling the virtues of some product because it abolishes free radicals or “reactive oxygen,” you know that you are dealing with some nonsensical marketing. Not science.

Fortunately, despite the marketing hype, it’s virtually impossible to obliterate all the free radicals in your body: Some must remain in your system or you will run into all kinds of medical problems.

Let me give you two examples of research that has shown first the good side of a producer of free radicals and second, one of the reasons why we know that there is more to aging than free radicals.

A study from France looked at a dye called mangafodipir that is used in MRI scanning. It was found to increase the cancer-killing ability of some chemotherapy drugs, while at the same time protecting normal cells. Mangafodipir was found to help promote the production of hydrogen peroxide while at the same time, through different biological mechanisms, protecting healthy cells from damage.

The second piece of research concerns my mole rats. I’ve talked about them before. They are extremely long lived: most reach the age of 25-30. And they seem never to get cancer. There are very few species that are spared from cancer: sharks rarely get the disease and there are some simpler organisms that also seem to be spared. So these mole rats have attracted the attention of researchers. What is more, they have very high levels of DNA damaged by oxidation so by rights they should get cancer and age prematurely. The fact that they don’t is leading to a whole new line of thinking about aging and illness.

So the message should be this: oxidative stress may be a factor in illness and aging, but your aim should be to modulate the free radical systems in your body, not to obliterate a key cancer killer.

Eat a diet that is rich in antioxidants
Don’t try and avoid stress: you can't. Learn to manage it
Take regular physical exercise
Avoid environmental toxins such as smoke, excess sunlight, pesticides and radiation

A New Way of Looking at – and Treating - Inflammation

Diseases of both large and small blood vessels are two of the biggest problem facing people with diabetes. Not only is it a huge clinical challenge, but also nature sometimes does our experiments for us. The high rates of coronary and peripheral vascular disease in diabetes can be seen as a kind of experiment of nature: a recognizable set of chemical abnormalities that might shed light on vascular diseases in general. It was those twin factors: a huge clinical problem, and an experiment of nature, that lead me to pick the topic of my research doctorate. 

When I was working on my research doctorate in the mid 1980s, I came across a lot of old research that seemed to show links between inflammatory and autoimmune conditions like systemic lupus erythematosus and rheumatic fever, and the eventual development of coronary artery disease. There was also a lot of old and largely forgotten research about the link between some viral infections and the development of coronary artery disease and acute coronary artery occlusions, because some infections can make blood more “sticky.” Inflammation evolved as one of the body’s defence mechanisms.

So I made the proposal – revolutionary at the time – that diabetes, coronary artery disease and a range of other illnesses might be inflammatory rather than degenerative. I soon found inflammatory markers in people with diabetes, that helped predict when someone was running into trouble with their eyes, kidneys or heart.  Even with stacks of data, I had to spend a lot of time defending that position, because it also implied that some illnesses thought to be irreversible might not be.

With the passage of time, it has tuned out that I was probably correct. Chronic inflammation, wherever it starts, mat have long-term effects on the body and on the mind. Chronic inflammation increases the risk of diseases of many blood vessels, as well as causing anemia, organic depression and cognitive impairment. Here is a partial list of common conditions in which inflammation is a prominent factor:
1.  Rheumatoid arthritis
2.  Systemic lupus erythematosus
3.  Fibromyalgia
4.  Chronic infections
5.  Insulin resistance or metabolic syndrome
6.  Arteriosclerosis
7.  Diabetes mellitus
8.  Hypertension
9.  Asthma
10. Inflammatory bowel disease
11. Psoriasis
12. Migraine
13. Peripheral neuropathy
14. Alzheimer’s disease
15. Autism
16. Gingivitis
17. Cystitis

The reason for raising the issue is not to say “told you so!”

It is instead that we need to think about inflammation a little differently. There is a mountain of information about the physical aspects of inflammation. We can stop at the simple description of inflammation as a condition in which part of the body becomes reddened, swollen, hot, and usually painful, or we can look below the surface: we can examine inflammation not only as a physical problem, but also as a psychological, social, subtle and spiritual problem. Why bother? Because the deeper approach allows us to understand and to treat and transcend inflammation as never before.

I am going to write some more about specific ways to address inflammation and what it means in future articles. I would also like to direct you to the book Healing, Meaning and Purpose, in which I talk about specific approaches in more detail.

But I would like to start with this.

In Ayurvedic and homeopathic medicine, inflammation is a sign of an imbalance in the vital forces of the body, and the traditional Chinese system agrees: here inflammation is usually a manifestation of an excess of Yang Qi, or a deficiency of Yin Qi. Most of our lives are seriously out of balance: Yang Qi is like a rampaging lion that has been stimulated by:
Acidic foods;
Environmental toxins;
Unwanted sexual stimulation:
Noise;
Discordant music:
Constant demands from others:
Toxic relationships;
Years spent in front of television sets and limitless multi-tasking.

It should be no surprise to learn that all of these inflammatory conditions are increasing rapidly throughout the Western world. Not because we are getting better at identifying them, or we are living longer, but genuinely increasing.

It is wrong to put all the blame on poor diets or inadequate exercise. The problem is more subtle and is a reflection of distorted Information being fed to our bodies, minds, relationships, subtle systems and spiritual relationships.

The great news is that this simple conceptual shift gives us a whole load of new tools for handling these problems, and for using them as catalysts to growth.

In the next few weeks, I am going to drill down and give you some specific guidance that ties into the material in Healing, Meaning and Purpose and the next two that are on the launch pad.

Fasten your seat belt!

Technorati tags: Inflammation Aging Alzheimer's disease Arteriosclerosis Neuropathy Autism Arthritis Systemic lupus erythrmatosus Fibromyalgia Inflammatory bowel disease Gingivitis 

Add Years to Your Life and Life to Your Years: The Power of Small Changes.

I want to tell you about a mind bogglingly important study that many professionals have known about, but somehow hasn’t popped up on most people’s radar. The story  was broken by the BBC last month. It is about an exceptionally important study that has been running in Norfolk, in Eastern England, as well as other parts of Europe since 1992. The British section is directed by Professor Kay-Tee Khaw who is Professor of Clinical Gerontology at the Department of Public Health and Primary Care at the University of Cambridge. The main focus of the Clinical Gerontology Unit is the maintenance of health in aging populations, with a particular emphasis on the combined role of lifestyle, environmental and genetic factors in chronic diseases.

The UK arm of the study has been following 25,663 men and women aged between 45 and 79 years old, looking at their diet, environment, lifestyle and health. The latest results from the study have confirmed several things that we already suspected: 1. Eating five portions of fruit and vegetables a day can give you the life expectancy of someone three years younger.
2. Not smoking turns back the clock by four to five years.
3. Even increasing exercise by a moderate amount can increase your life expectancy by three years. But the amount of exercise someone would need to do to achieve that depends on their job. A sedentary office worker would need to do one hour of exercise, such as swimming or jogging every day. By contrast, a person with a moderately active job, such as a hairdresser, would need to take 30 minutes of exercise a day. Here’s some more good news: People with very active jobs, including nurses and bricklayers, do not need to do any extra exercise - as their work is strenuous enough.

I think that just about anyone can take those baby steps toward a longer and healthier life

There's an old Yugoslavian Proverb:
“Grain by grain a loaf, stone by stone, a castle.”

That seems about right!

Technorati tags: Health Longevity Preventative medicine Wellness

The Status Syndrome

I have recently seen some reports in the media about a connection between money and longevity: the idea being that the more money you have, the longer you live. Which presumably means that Bill Gates will live forever. Sadly this link between wealth and longevity is a false extrapolation from some very old research. Yes, extreme poverty is associated with excess mortality, not only because of poor lifestyle and lack of access to medical screening and care, but also because adults who were of low birth weight are more likely to develop diabetes and hypertension. And people born into poverty are more likely to have been malnourished before birth, and therefore to be of low weight at birth. This relationship between low birth weight and subsequent disease is likely the result of incomplete development of the liver and kidneys before birth.

A famous study of British civil servants has indeed shown that people who work in more senior positions are more likely to live longer than people working in the lower ranks. But it has nothing to do with money. Once people have passed a certain critical material threshold, lifestyle factors have progressively less impact. There are still more smokers amongst manual workers and hours of hard work means that they have to eat high calorie high fat foods to be able t keep working, and we have not done a good job of showing people how easy it is to eat healthily on a budget.

Sir Michael Marmot is an outstanding epidemiologist working in London, who has spent three decades examining the health consequences of differences in social standing. He has discovered that there is a social gradient that predicts health outcomes: the lower a person’s social rank, the higher their risk for heart disease, diabetes, mental illness, accidents and many other health problems. Once people have passed a certain threshold of physical and material well-being, something else comes into play: other kinds of well-being that have a massive impact upon life. These are autonomy - how much control you have over your life - and opportunities for social engagement and participation. The psychological experience of inequality has profound effects on multiple body systems. Sir Michael has summarized a lot of his research in an eminently readable book entitled, appropriately, The Status Syndrome.

There is an interesting corollary of the Status Syndrome. In his book The Pecking Order, Dalton Conley presents interesting research that indicates that our level of success relative to our siblings is less the result of birth order or genetics and more the result how much family resources – time, energy, money and love - we received while growing up.

There’s not much that you can do about your birth order, but all this research has some important implications.

1. Once you have crossed a threshold that allows you access to nutritious food, exercise, stress management and health care, there is no longer any link between health and wealth. In fact, working and working to get more and more money is associated with increased mortality!

2. The amount of time, energy, money and love that the family is able to give to each child will help shape and structure their future life. That is a hugely important responsibility.

3. Ensure that you feel and know that you are autonomous: that you are in control of your life. I really urge you to work on this. One of the reasons for being concerned about the ever-increasing demands being made upon all of us is that it can make us feel out of control. I spend a great deal of time in Healing, Meaning and Purpose discussing and demonstrating techniques for taking back control of your life.

4. Are you socially engaged and participating in life? Are you doing something for your community or your church? How often do you meet new people and engage with them? Is there someone whom you haven’t seen for a while that really needs a call from you? Please do think about this: it’s not just about socializing; it’s about protecting your health and well-being, and the health and well-being of those around you.

Technorati tags: status syndrome, Michael Marmot

Integrated Health and Aging

An important principle of the emerging laws of health and healing is that anything helpful should help more than one system of the body at a time. So a diet that might help mitigate the effects of aging in the skin should also have beneficial effects on the major organs of the body.

So I was encouraged to see a new report indicating that cardiovascular health and a healthy lifestyle are associated with maintaining the health of our brains as we age. This is, of course, intuitively obvious, but it is always nice to see such things confirmed by empirical research.

The new report is from a multi-Institute collaboration of the National Institutes of Health (NIH) published online in Alzheimer's & Dementia: The Journal of the Alzheimer's Association. The chair of the committee was Hugh Hendrie, the Scottish-born professor of psychiatry from the University of Indiana, and the committee members were many of the most eminent people in the fields of aging and Alzheimer’s disease.

What is encouraging about this new report is that many of the factors associated with cognitive decline as we get older are eminently remediable: we have within our reach a set of potential interventions that could significantly reduce our personal risk of developing cognitive problems later in life. These are the things that we need to work on if we want to reduce our risk of developing cognitive decline later in life:

1. Hypertension: There is excellent evidence that inadequately treated hypertension correlates strongly with cognitive decline.
2. Physical activity: There is good evidence that elders who exercise regularly are less likely to experience cognitive decline. This is over and above the general improvement in quality of life that accompanies regular exercise. The earlier in life that we start, the easier it is to continue.
3. Increased mental activity throughout life, including learning new things and going through higher education may benefit the health of the brain.
4. Moderate alcohol use and the use of vitamin supplements also seem to be brain protectors, though the report does not specify which supplements.
5. Social disengagement and depressed mood are both associated with poorer cognitive functioning, so it is important to be alert to signs of depression, and to maintain a social network. I discuss this in more detail in my book Healing Meaning and Purpose.

There are doubtless some genetic and environmental factors about which we can do little. But the idea that we now have a list of things that we can do to protect our brains is very exciting.

This report also signals another important change. In recent years we have seen the growth of Positive Psychology, the study of how to improve ourselves rather than the constant focus on psychopathology. This report calls for the research community to study health maintenance of the brain with the same energy that it has brought to bear on the study of diseases of the brain. To which I would add, that we must not just focus on how to maintain the health of the brain, but how we can enhance it’s function so that we can all reach and exceed our full potential.

Technorati tags: aging, Integrated health, Positive Psychology, healthy lifestyle,

A Rainy Day Question

“Millions long for immortality who do not know what to do on a rainy Sunday afternoon.”---Susan Ertz (a.k.a. J.R. McCrindle, Anglo-American Novelist, 1894-1985)

I was reminded of this quip while reading some new material about the progress being made in aging research. Speaking at the annual meeting of the American Association for the Advancement of Science in St. Louis, biologist Shripad Tuljapurkar who holds the Dean and Virginia Morrison Professor of Population Studies at Stanford University highlighted some of the issues surrounding the extension of human life-span. This is something that I have been tracking closely for over twenty years, since it was shown that the cells of people with diabetes mellitus age more quickly when placed in tissue culture, even if they are away from the high glucose of the diabetic environment. There is a link between premature aging and diabetes.

It is widely known in the scientific community that there has been a great deal of progress on aging research, much of it done behind the closed doors of pharmaceutical companies. According to Professor Tuljapurkar between 2010 and 2030, the modal, or most common, age of death will increase by 20 years if anti-aging therapies come into widespread use. This projected increase is based on some sophisticated modeling, and reflects a life-span growth rate that is five times faster than the current rate. If accurate, this would increase the modal age of death in industrialized countries such as the United States from roughly 80 years to 100.

So back to the question: if you suddenly discovered that you were going to have an extra thirty years of healthy life, what would you do with it?

I really do suggest that you start thinking about that. Assuming that you have enough money to live a decent life, what would you do with that extra twenty years? Would you:

1. Enjoy spending more time with younger members of the family?

2. Learn some new skills?

3. Make new friends?

4. Travel?

5. Read those books you always meant to?

6. Become more involved in spiritual pursuits?

7. Find a new way of serving others?

    8. Sit in front of the television?

What plans or aspirations do you have that you want to add to this list?

But then I have another question for you: if your answers included any of the points from 1-7, why not do them right now? What exactly is stopping you from doing all those things today?

Technorati tags: living, dreams, meaning, purpose

The Four Percent Solution

In this week’s edition of the Journal of the American Medical Association, is a study of 11,701 American over the age of 50, who participated in a national health survey in 1998 funded by the National Institute on Aging. The researchers analyzed participants' outcomes during a four- year follow-up and examined the health characteristics that seemed to predict death within four years.

These were the questions that were asked, and this is a bit like golf: you want to have the lowest score possible. Zero would be best. The score is supposed to tell you your chance of dying within the next four years.

1. Age: 60-64 years old = 1 point; 65-69 = 2 points; 70-74 = 3 points; 75-79 = 4 points; 80-84 = 5 points; 85 and older = 7 points.

2. Male or Female: Male = 2 points.

3. Body-Mass Index: Less than 25 (normal weight or less) = 1 point. (BMI = weight in pounds divided by height in inches squared, multiplied by 703.)

4. Diabetes: 2 points.

5. Cancer (excluding minor skin cancers): 2 points.

6. Chronic lung disease that limits activities or requires oxygen use at home: 2 points.

7. Congestive heart failure: 2 points.

8. Cigarette smoking in the past week: 2 points.

9. Difficulty bathing/showering because of a health or memory problem: 2 points.

10. Difficulty managing money, paying bills, keeping track of expenses because of a health or memory problem: 2 points.

11. Difficulty walking several blocks because of a health problem: 2 points.

12. Difficulty pushing or pulling large objects like a living room chair because of a health problem: 1 point.

Score:

• 0 to 5 points = less than a 4 percent risk of dying;
• 6-9 points = 15 percent risk;
• 10-13 points = 42 percent risk;
• 14 or more points = 64 percent risk.

So what should we make of this?

The first thing is that the study is just looking at the physical aspect of life. It asks nothing about diet or family history. It also says nothing about psychological and spiritual factors that can buttress health and well-being.

So what should it mean if somebody gets a high score? Does it mean that they should expect the end and stop reading long novels? Absolutely not! A high score should be a very good indicator that you should have a talk with your health care provider and get to work on all the reversible factors on the list. And as I have pointed out before, a positive psychological outlook and regular spiritual practice have been shown to extend the length and quality of your life.

It is not given to us to know the length of our lives and plenty of people live on and on despite breaking all the rules while others die young despite a lifetime of temperance. I had an aunt who smoked heavily throughout her adult life, yet lived to be well over ninety, while one of my former students died of lung cancer in his thirties, having never smoked a single cigarette.

Genes and lifestyle are important in determining our life span, but so are the quality and integrity of our relationships, our own sense of meaning and purpose, the clarity of the subtle systems of the body and our spirituality.

So use this study not as a death sentence, but as a wake-up call.

Technorati tags: health quiz, aging, longevity

Aging in Style

It happens to all of us as we reach a certain vintage, that we begin to wonder how we will engage with and negotiate the inevitable process of aging. Billions of dollars a year are spent on trying to avoid the inevitable, and we are seeing people who have had not one, but layers of cosmetic surgery, botox and an array of other attempts to postpone or camouflage the effects of the passage of time.

For over two decades Andrew Weil has been one of the most sensible voices in the field of whole-person medicine, and he has recently turned his attention to aging, driven in part, as he says, by himself passing age 60 in 2002. His latest book Healthy Aging is full of common-sense ideas and is well worth reading. His approach to healthy aging was described in an article in the Washington Post by Agigail Trafford.

In a nutshell: Learn to breathe deeply, eat fruit and vegetables, walk, dance, play golf, do yoga, develop a positive mental attitude, learn a second language, get a massage, put fresh flowers in the house, be sure to love, and pay attention to spiritual health. He also makes another point, which is brought out in the Washington Post article, but has not been in many of the other reviews of the book. Weil is firmly of the view – as am I – that there has been altogether too much emphasis on personal responsibility for poor health choices, and not enough on an individual’s genetic predisposition to some problems, like obesity, as well as social and environmental pressures. As a "for instance," there has been a chronic lack of governmental and corporate will to improve the quality of food or to encourage exercise. Though I think that this was written before the Department of Agriculture’s new initiatives on healthy living, which are making bold, if belated, attempts to improve the quality of life of people not just in the United States but around the world. And Weil points out that many Departments of Government have a part if we are to improve the prospects for healthy aging.

It is difficult to disagree with any of these things. But I have two nagging worries about his book, though to be fair, I suspect that he would agree with me about both.

The first is that what he proposes is mainly something for the relatively affluent classes. Although I have no problem with a counsel of perfection, I wonder how realistic are his plans. I have spent years trying to help people in the most deprived circumstances, and for many of them, the prospects that they will be able to find or afford healthy nutrition are scant, and even walking outside may be dangerous. That is, of course, why we need corporate and Government help.

The second point is about acceptance: accepting the passage of the years with grace, serenity and equanimity, instead of fighting the inevitable. Of accepting that increasing age can be a time of deepening spiritual insights and of the progress growth of understanding and wisdom. I know that is Weil’s position, and it comes up in the later stages of his book, but I would hate to see such an important aspect of healthy aging lost in the rush to try his sage advice about diet, sleep and supplements.

Technorati tags: Andrew Weil, aging, healthy lifestyle