Richard G. Petty, MD

Vitamin D and Interstitial Cystitis

I think that interstitial cystitis (IC) must be one of the most distressing of conditions to have, and it is certainly one of the most challenging to treat. Outside the United States, it is more often called painful bladder syndrome (PBS).

IC is a condition that results in recurring discomfort or pain in the bladder and the surrounding pelvic region. The symptoms vary from person to person and even in the same individual. It can vary from an experience of mild discomfort, pressure, tenderness, to intense pain in the bladder and pelvic area. Symptoms may include an urgent need to urinate (urgency), a frequent need to urinate (frequency), or a combination of these symptoms. Both may be severe: I’ve seen people who had to urinate every ten minutes. Pain may change in intensity as the bladder fills with urine or as it empties. Women's symptoms often get worse during menstruation, and some experience pain with vaginal intercourse. There is a good website provided as a service of the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK), that is fairly up-to-date.

Because IC varies so much in symptoms and severity, most researchers believe that it is not one, but several diseases. There are clear links between IC and fibromyalgia, irritable bowel syndrome and chronic fatigue, and probably many other illnesses.

There is good evidence that inflammation in one pelvic organ can cause pain in other organs that share some of the same nerve supply. Inflammation of the colon may make some nerves coming from the spinal cord hyper-excitable, which in turn makes nerves running to the bladder hypersensitive. Because the same nerve plexus connects with the ovaries and uterus, it is no surprise to learn that phases of the menstrual cycle impact the way in which inflammation in one pelvic organ can cause inflammation in another.

IC appears to be becoming more common, although that is always a risky comment, because it was undoubtedly not often recognized in the past. The old teaching was that it was only something that occurred in menopausal women, but it is now being diagnosed in men as well as women, and in people as young as their late teens.

The cause of IC remains unknown, though there have been many theories: infections, allergy, autoimmunity, neurological and genetic. There have been recent claims of the discovery of responsible genes, but hey would most likely be susceptibility genes, rather than causative. Otherwise why should the rates of IC genuinely seem to be increasing? What seems clear is that the normal mucus lining of the bladder wall is damaged.

Multiple types of treatment have been tried, from medication to pelvic floor exercise, to neurological implants and homeopathy and acupuncture. The report of anything new that may help is always welcome.

So I was interested to see a report from investigators in Milan on the efficacy using a molecule that has been attracting a lot of interest recently: vitamin D. The active form of vitamin D is known as calcitriol or 1,25-dihydroxycholecalciferol (1,25(OH)2D3) that is manufactured in the kidney. Its in vivo biological effects include regulation of bone metabolism, control and modulation of the proliferation of cells and some aspects of the immune response. These characteristics have already led to therapeutic applications in osteoporosis, secondary hyperparathyroidism, and psoriasis. Many reports show beneficial effects of vitamin D in animal models of diabetes, organ graft rejection, experimental allergic encephalomyelitis, lupus nephritis, and in asthma. Despite what you may have seen in some advertisements, just taking extra vitamin D does not help, and may make matters worse: they key is to have the right form of vitamin D, that can reach and affect the right areas of the body.

The Milan team used a vitamin D3 analogue (BXL628) in a mouse model of chronic cystitis. What they found was that a specific inflammatory marker in the blood went down with treatment, and at the same time histological analysis showed a decrease in edema and white blood cell (leukocyte) infiltration in the bladder wall. This and some other biochemical evidence of what is known as “mast cell degranulation,”  is very encouraging and strongly supports the potential therapeutic use of BXL628 in diseases such as human interstitial cystitis.

This is the kind of mechanism-based research that holds out enormous promise for everyone’s welfare and will help us in our goal of using science to inform the development of the next generation of treatment, health and wellness.

Psychiatric Illnesses and Fibromyalgia

There’s an interesting and important article in last month’s issue of the Journal of Clinical Psychiatry, by a group of investigators from the University of Cincinnati.

They have shed important new light on fibromyalgia. We’ve recently learned how it is linked to disturbances of the serotonin transporter, as well as anti-inflammatory proteins, and that is may respond best to the kind of comprehensive multi-leveled approaches that we use in Integrated Medicine.

The new research compared people with fibromyalgia with people with rheumatoid arthritis, and it found that fibromyalgia, but not rheumatoid, may be associated with a range of psychiatric illnesses:

1. Major depressive disorder
2. Bipolar disorder
3. Comorbid anxiety disorders including panic disorder, social phobia, posttraumatic stress disorder and obsessive-compulsive disorder
4. Eating disorders and
5. Substance abuse

What was particularly important in this study was that the psychiatric problems usually preceded the onset of fibromyalgia. So it wasn’t that people were developing psychological problems because they were in chronic pain.

It’s beginning to look as if fibromyalgia is part of a larger group of disorders that all share common etiologies or causes. Family studies have indicated that fibromyalgia and mood disorders share some of the same - perhaps genetic - determinants.

The study also confirms what we have said before: fibromyalgia is not only associated with some psychiatric problems, but also with other medical disorders, several of which may also co-exist with the same psychiatric problems. They include:

1. Chronic fatigue syndrome
2. Irritable bowel syndrome
3. Interstitial cystitis
4. Multiple chemical sensitivities and
5. Migraine

Not only does this research highlight the need to check people with fibromyalgia to see if they might also be struggling with a psychiatric problem, but it is helping us home in on some of the mechanisms linking these apparently separate problems.

This particular study was done mainly in white women, and the investigators knew who had fibromyalgia, so there’s more work to be done.

But if you or a loved one is struggling with fibromyalgia, it is good news to know that we are making rapid progress in unraveling this horrible illness.

Irritable Bowel Syndrome, Mood Disorders, the Serotonin Transporter and Integrated Medicine

Whenever we run into two common conditions, it’s easy to imagine links where none really exists. Three years ago some colleagues from Oxford reported on a person with bipolar disorder and irritable bowel syndrome, and commented that the association was uncommon.

However there may after all be a genuine link between mood disorders and irritable bowel syndrome, that is a disturbance in the “third arm” of the autonomic nervous system. The first arm is the sympathetic nervous system, the second the parasympathetic and the third is the enteric or gut nervous system that is closely linked with key regions of the brain.

Not long ago there was an interesting report of a woman who had multiple problems including environmental allergies, atypical bipolar disorder, irritable bowel syndrome and Raynaud’s phenomenon. Such odd constellations of problems are quite familiar to anyone working in the major referral centers around the world, and some can be exceedingly hard to treat. Tough cases like this often stimulate further research. I once tried and failed to treat a woman with a chronic illness. When she came back a year later to see if I had any new ideas, I told her that I now had a shelf of books and over a thousand reprint of papers about her condition: I don’t like failing someone. And I’m not unique in that.

A new study from the Karolinska Institute in Stockholm, has found that chronic widespread pain, which, as I explained recently, is the cardinal symptom of fibromyalgia, is prevalent and co-occurs with other symptom-based conditions such as chronic fatigue syndrome, joint pain, headache, irritable bowel syndrome, and psychiatric disorders. There is more and more evidence of a link between fibromyalgia, irritable bowel syndrome and depression. It is not just that people are sick and get depressed: as we shall see in a moment, the link is more subtle than that. Another illness seemingly linked to these three is interstitial cystitis.

Now some colleagues at the National Institutes of Health have been looking at a serotonin transporter (SERT) that regulates the entire serotoninergic system and its receptors. This transporter is found throughout the animal kingdom, telling us that it must be important.

In humans the gene is located on chromosome 17, and disturbances in it have been found in people with autism, ADHD, Tourette’s syndrome and bipolar disorder. Experiments using genetic engineering suggest that SERT may be a candidate gene for several human disorders, from obesity to irritable bowel syndrome. People who have disturbances in SERT tend not to respond so well to the serotonin reuptake inhibitors (SSRI’s) antidepressant medicines.

SERT is not the whole story. Some geneticists from Los Angeles have found evidence linking irritable bowel syndrome, depression, migraine and inheritance of mitochondrial DNA.

Many approaches have been tried to help people with these groups of problems. I always find it remarkable that psychological treatments can be so effective in conditions with a genetic component, for this once again proves that biology is not destiny.

The best approaches to conditions like irritable bowel syndrome and coexisting mood disorders is to use medications and psychological approaches. Many of us have also found that the addition of nutritional, environmental and subtle energetic approaches have been of great help, together with some work to uncover the meaning and transpersonal value of a chronic illness. That last piece is not the first priority, which is to help the person gain control of his or her life. But if we don’t do something to work with the meaning and purpose of an illness, it will usually come back in some form or other. This comprehensive approach differentiates Integrated Medicine from many other types of therapy.

Chronic Fatigue, RNase Deficiency and Spiritual Development

I was very sorry to hear that Ken Wilber, whose work I admire enormously, has recently been very unwell. While weakened by an underlying chronic illness, he took a nasty fall that has left him pretty badly bruised, and with some possible neurological problems. Fortunately he is already somewhat better.

According to Ken, his underlying illness is a form of chronic fatigue syndrome called or caused by RNase-L Enzyme Dysfunction. People with the problem develop a number of bizarre symptoms apart from fatigue, including muscle weakness, fevers and immune dysfunction. The RNase enzyme is normally activated when a cell has to deal with viruses, some toxins and some bacteria. There is a good introduction here.

There is a growing literature on the subject: investigators from Brussels have recently shown a link between exercise performance and immune dysfunction in some of these patients. It may be that elevated RNase-L enzyme activity may provide us with a biological marker for some cases of chronic fatigue syndrome. Despite this research, I still have many colleagues who continue to say that chronic fatigue syndrome and a probably related condition, Chronic Fatigue and Immune Dysfunction Syndrome, are purely psychological problems.

I am quite sure that they are wrong.

Not least because there are very few illnesses that can be reduced to just psychological or just physical causes. These artificial distinctions do little to help people suffering with genuine problems. (You may be interested to have a look at a brief piece that I wrote about this artificial distinction.)

I do know that the most difficult problems that I have ever faced in clinical practice have been the chronic fatigue syndromes and a possibly related problem: interstitial cystitis. The only things that have helped have been approaches employing the five dimensional approach: physical, psychological, social, subtle and spiritual.

And now I’m going to go out on a limb and do something that normally I do not. I will normally not make even the broadest comments about someone’s diagnosis and treatment unless I’ve seen them myself: there are few things worse than people trying to diagnose at long range and when they only have half the information. But when I see symptoms like these: fatigue and fever, physical weakness and sometimes profound psychological effects, I have to ask whether the biochemical markers are actually telling us something different: that some people with these problems may actually have what used to be known as “diseases of discipleship.” An old-fashioned term used to describe some of the physical challenges and changes that may accompany spiritual evolution. If I am correct, I would predict that Ken - and many other sufferers - should also have profound disturbances of their normal circadian rhythms, some predictable but subtle endocrine disturbances, and otherwise inexplicable sensations roughly corresponding to the channels identified in Chinese and Ayurvedic medicine.

One of the most startling recent discoveries in medicine has been that some of the time-honored laws of healing are changing, because we are ourselves changing very rapidly. In Healing, Meaning and Purpose, I spent a long time talking about some of the reasons for coming to that understanding, and how to use it to improve our health and well-being. I fully expect to spend the remainder of my career showing people how these new laws and principles can help us all, as well as ensuring that appropriate research continues to help us develop these new understandings about health and wellness.

So I’m going to suggest that Ken’s problems might never have happened if he hadn’t been on such a deep spiritual quest, and if he hadn’t been turning up a lot of answers that matter.

Get well Ken!

Technorati tags: Ken Wilber Chronic fatigue syndrome RNase deficiency Chronic Fatigue and Immune Dysfunction Syndrome Interstitial cystitis Spiritual development Circadian rhythm Integrated medicine Integrative medicine Laws of Healing 

Cranberries and the Inflammation Associated With Severe Gum Disease

There is an interesting study from a team of researchers from Quebec, Canada. The findings, published in the Journal of Antimicrobial Chemotherapy, reveal that natural compounds in cranberries may help ward off periodontitis, or severe gum disease, by serving as a powerful anti-inflammatory agent. This anti-inflammatory effect may be attributed to unique compounds in the fruit that prevent the bacterium P. gingivalis from adhering to the teeth below the gum line. Though it is early days, this new research offers promise for the estimated 67 million Americans affected by periodontitis, the primary cause of tooth loss in adults.

The reason for the study was that cranberries have what are known as "anti-adhesion" activity. This helps guard the body from certain harmful bacteria that cause urinary tract infections (UTIs), gastric ulcers and gum disease. This anti-adhesion activity is primarily due to molecules called proanthocyanidins (PACs) found naturally in cranberries and other foods. Cranberry PACs contain a unique A-type structure that is responsible for this anti-adhesion mechanism of action, while most other foods contain only the more-common B-type PACs.

Researchers discovered that cranberry compounds can reduce the growth of P. gingivalis and subsequent plaque development -- the initial step in the development of periodontitis. Periodontitis occurs when inflammation or infection of the gums is left untreated or treatment is delayed. Infection and inflammation spreads from the gums to the ligaments and bones that support the teeth and eventually leads to tooth loss.

In a paper in the Journal of Dental Research the same researchers had previously shown that cells treated with cranberry juice showed significantly less inflammation than cells that were not treated.

Not only can cranberry compounds decrease the growth of P. gingivalis, they may also prevent certain oral bacteria from directly destroying gum tissue itself -- another major factor contributing to periodontitis. This may have more widespread implications as recent studies have also linked severe gum disease with an increased likelihood for heart disease and stroke.

The study was part funded by the Ocean Spray agricultural cooperative that sells cranberry juice.

Brushing, flossing and regular professional cleaning reduces the risk of developing periodontitis by helping to prevent the onset of gingivitis, or gum infection. Cranberries may provide an interesting ingredient in the development of new therapeutic approaches for treatment of periodontitis.

Technorati tags: Cranberries Dental disease Heart disease Urinary tract infection Inflammation

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