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.

A Missing Link: Serotonin, Inflammation and Psychiatric Illness

We have previously looked at the extraordinarily high rates of inflammation in psychiatric illnesses, as well as the evidence implicating disturbances in the serotonin transporter and an array of psychiatric and physical illnesses, including fibromyalgia and irritable bowel syndrome. Disturbances in serotonin homeostasis as well inflammation-promoting (pro-inflammatory) cytokines have both been implicated as causative factors in major mental illness. So the hunt has been on to see if there’s some way of uniting these two causative pathways.

There’s an exceptional important paper out this week in the journal Neuropsychopharmacology.

Investigators from the Vanderbilt University School of Medicine in Nashville, Tennessee, have established that the pro-inflammatory cytokines interleukin-1beta and tumor necrosis factor-alpha activate serotonin transporters. Using rat cells, they were able to show the precise mechanism by which these cytokines could regulate the activity of the serotonin transporter.

So why is this so important? Not only does it open up several new options for treating mental illness, but it may also explain some puzzles.

It’s recently been shown that mental illness is more common in overweight people. Large amounts of fat in the abdomen act as a kind of inflammation factory, soaking the circulation in inflammatory mediators. So here we have a link between ever expanding waistlines and the increasing rates of mental illness in the population. It’s not just stress and environmental overload; it is likely also fat causing inflammation.

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.

Probiotics: Caveat Emptor

You may well have heard the advice that we all need to keep the bacetria in our intestines healthy. Countless experts have recommended that, as long as we are not lactorse intolerant, we should regularly take some live yoghurt to "re-colonize" our intestines with nice friendly bacteria.

There has just been a briefing in London to warn the public that as many as half of the "probiotic" or "friendly bacteria" products on sale in the United Kingdom could be ineffective and some may even be harmful.

The experts on the panel included Professor Glen Gibson from the University of Reading who is an expert in food microbiology, and recommended sticking to products made by major manufacturers. Too many of the other productsmight not contain the numbers of bacteria advertised, and the icrobes might not survive long enough in the intestines to do much good.

The evidence that probiotics help is still far from settled, as discussed in a recent review. But there are enough reports to think that probiotics may be helpful for irritable bowel syndrome and perhaps inflammatory bowel disease.

An even newer area or interest in the use of "prebiotics:"  short-chain carbohydrates that alter the composition, or metabolism, of the intestinal organisms in a beneficial way.

Make sure that if you are using a product, it comes from a reputable manufacturer, and that it contains at least 10 million bacteria. And as I said in my title, "Caveat Emptor," "Let the buyer beware."

How Does Fiber Help You?

Unless you’ve been living on Mars (!), you will doubtless have heard of the advantages of increasing the amount of fiber in your diet. A high-fiber diet reduces your risk of colon cancer, constipation, hemorrhoids hypercholesterolemia and insulin resistance syndrome.

We have always wanted to know how fiber does so many magical things at once, and now we may an answer. In a paper published in the open-access Public Library of Science Biology today, by a group from one our local institutions – the Medical College of Georgia in Augusta – collaborating with a researcher from Josai University, Sakado, Saitama in Japan.

The epithelial cells lining the intestine have a life span measured in 1-5 days. They spend their short life times working to process enormous amounts of food residue on its way past. It is this layer of cells that acts as the barrier between the body and items floating past on the inside of the intestine.

Long before it became the topic of some popular books are over-enthusiastic magazine articles, we became very interested in the idea of the “Leaky gut:” the concept that some illnesses are a result of breakdown of the normal integrity of this protective barrier. Over 20 years ago, a friend and colleague at Northwick Park Hospital – Ingvar Bjarnason – did some pioneering work on this important issue. Several recent studies have indicated that a breakdown of this barrier may be involved in several childhood illnesses including allergies and asthma. There is also some early information suggesting that “leaky gut” may be involved in some autoimmune processes involving the intestine. Both zinc supplementation and oats may prevent gut leakiness under certain very specific circumstances.

When the epithelial cells in the gut wall encounter indigestible fibrous foods, the outer covering of the cell ruptures, releasing a coating of cell-protecting mucus. In a matter of seconds, the cell begins to repair itself, in the process releasing yet more of the beneficial mucus. Not only does it lubricate, but also it may keep some carcinogens and allergens out of your system.

The constant buffeting of the cells causes mild damage that increases the level of lubricating mucus. Injury at the cellular level promotes the health of the gastrointestinal tract as a whole.

Here we see a basic principle of nature: many of the same things that apply in the cells of the body apply equally in the life of someone trying to achieve success. Without the buffeting, the cells of the intestine could not produce the mucus on which your life depends.

Without some occasional adversity, you will find it more difficult to grow as a human being.

“Storms make oaks take deeper root.”
— George Herbert (English Religious Poet, 1593-1633)

“He who knows no hardships will know no hardihood. He who faces no calamity will need no courage. Mysterious though it is, the characteristics in human nature which we love best grow in a soil with a strong mixture of troubles.”
–Harry Emerson Fosdick (American Clergyman, Writer and Broadcaster, 1878-1969)

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.


Fibromyalgia can be one of the most difficult of clinical problems. Sadly this illness or group of illnesses is often dismissed as no more than a series of symptoms caused by depression, and people then do not get the treatment that they need. Fortunately we are now seeing the emergence of consensus guidelines on how to diagnose the problem.

Fibromyalgia is a common syndrome of chronic pain and fatigue, but it is a great deal more than just pain. It may affect many systems of the body, and depression and cognitive symptoms are common.

One of the key difficulties in people with fibromyalgia is a disturbance in pain thresholds. There has also been a lot of interest in the idea that people with fibromyalgia are “hypervigilant,” as a result of disturbance in the serotonin pathways in the brain. Something similar happens in many people with other types of chronic pain, particularly low back pain. The problem with all of this research has always been the chicken and egg problem: how many of these abnormalities are due to having chronic pain, and how many might be the cause of the problem?

As an example, I was treating someone with fibromyalgia, and as part of the package of treatments, she was to have acupuncture. If practiced by a professional, acupuncture is usually painless. I had not seen anyone experience pain from the treatment in many years; however, this person was so sensitive that even gentle tapping was excruciatingly painful for her. I have colleagues who take this to be evidence that the whole thing is psychological. But I am sure that they are not correct. To a neurologist this is wrong on three counts:
1.    There is a lot of data indicating metabolic disturbances in people with fibromyalgia that is quite different from anything seen in anxiety or depression. These include reductions in the activity of the cellular powerhouses – the mitochondria – as well as subtle effects in blood flow.

2.    A number of other illnesses, like migraine, are associated with changes in pain threshold, indicating a disturbance in the mechanisms that control pain sensation, either in the brain stem on the thalamus.

3.    This notion that “it’s psychological rather than physical,” harks back to the kind of dualism that is not very helpful.

Recent research  indicates that although fibromyalgia is a little more common in women, the old view that it is predominantly a female illness is not correct. There are also some strong associations with other illnesses, including depression, anxiety, headache, irritable bowel syndrome, chronic fatigue syndrome, systemic lupus erythematosus, and rheumatoid arthritis.

In the days that I treated a great many individuals myself, I always found that fibromyalgia and chronic fatigue syndrome were amongst the most difficult.

I’ve long been interested in the links between sleep disturbances and fibromyalgia as well as the modest improvement in people with a meditation program.  There is also another factor that is often not much talked about: people with chronic pain, from whatever cause can develop pain cycles: pain begins in some part of the body, but is then maintained by neurological circuits in the spinal cord and brain. Interfering with these pain cycles for even a day or two can sometimes be very helpful.

Fibromyalgia is one of the groups of conditions in which combinations are key. Trying just to use a medicine or just a diet is rarely likely to be crowned with success. The most helpful strategies that we have found have been combinations of:

  1. Physical care:
    1. Appropriate medications to help with pain transmission and symptoms of depression
    2. Sleep hygiene, and some of the other approaches that I’ve suggested for dealing with disrupted sleep.
    3. Low intensity exercise
    4. Nutrition: this one of the clinical conditions that first persuaded  me that there are some people who have genuine food and environmental sensitivities, and, in some rare cases Candida overgrowth. There are quite a number of foods that may be very helpful, depending upon the individual’s likes and dislikes.   
    5. I’ve had colleagues who’ve had some great results with herbal remedies and supplements, but there is little published  evidence that these work.      
    6. Some people seem to have biochemical disturbances that can be  helped with some of the Schussler tissue salts.
  2. Psychological support: there is some good evidence that some personality types and temperaments may be at increase risk of developing fibromyalgia, so any thing that helps build resilience and cope with negative cognitions can be very helpful. Some of the  tapping therapies can be very helpful adjunctive treatments, as can music therapy.
  3. People with fibromyalgia are often very sensitive to the people around them, and their nearest and dearest often need help in understanding how best to support the person with the illness.
  4. The subtle systems of the body are invariably compromised in people with fibromyalgia, and acupuncture – if people can tolerate it – as well as homeopathy can be very helpful. We have often used both together, though this is anathema to many classical homeopaths or acupuncturists. Perhaps they could not have been used in combination 50 years ago, but people have changed physically, psychologically, socially and energetically, and the rules have changed.
  5. As with most people struggling with chronic illness, many people with fibromyalgia lose contact with their Source. And this is why – in my books and recordings – I spend so much time helping people  re-establish meaning and purpose in their lives, and help them use the illness not simply  as a barrier to be overcome, but as a stimulus for internal growth. I have also seen a number of indivudals in whom fibromyalgia was symptommatic of a spiritual awakening.       

One of my biggest worries with fibromyalgia, as with so many chronic illnesses, is that many desperate sufferers and their families can become victims of the unscrupulous. I have seen countless people selling advice and treatments that have no basis in fact.

Not everything that I have discussed here is evidence based: there is so little research on things like acupuncture and homeopathy. But those are treatments to be used in combination with more conventional approaches. Using all together is usually the best way forward. And everything that I’ve discussed here has been used in working with hundreds of people around the world.

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