Beating Crohn’s and other Autoimmune Diseases

It had been a year since our oldest son, Wesley, had come down with some kind of mysterious illness.  After his fourth birthday he had gradually grown weaker and weaker and had stopped growing, had lost weight, and had to rest after walking no more than a few hundred feet at a time. Painful nodules would appear on his arms and legs just under his skin and last for weeks at a time. At one point he developed severe calf pain in both legs so that he could barely walk for a month or so. Then, he developed a perianal abscess that was extremely painful. It only resolved when Wesley happened to fall down just right and rupture it one day. However, he soon developed a second perianal abscess that did not resolve. During this time he also started having bloody stools where the blood would make the whole toilet bowel bright red.

Despite being a doctor myself, I could not figure out what was going on with Wesley.  What could be causing all of these symptoms?  His pediatrician thought that he probably had a begin colon polyp on top of some viral syndrome. Many members of my own family are also physicians, but they were equally mystified. My wife, Sigrid, an accountant (CPA), felt that Wesley probably had Crohn’s disease, since this difficult autoimmune condition (that primarily affects the gastrointestinal system) runs in her side of the family. However, I felt that Wesley was too young – especially since he had no abdominal pain or discomfort.  It wasn’t until Wesley’s surgeon suggested Crohn’s disease, after having drained Wesley’s perianal abscess without resolution, that we took his advice and headed for UC Davis for evaluation and a colonoscopy.

When I first saw the colonoscopy pictures, I was shocked.  They looked like pictures of hamburger to me. There were bleeding ulcers everywhere throughout much of his colon and the portion of the small bowel that attaches to the colon (and found out later that his stomach lining was also inflamed).  He had lost half of his blood volume and his inflammatory enzymes and his platelets were through the roof. He definitely had “very early onset Crohn’s disease” – and was therefore in for a lifelong struggle with much pain and many surgeries ahead of him.

During our week in the hospital at UC Davis getting Welsey’s abscesses drained and healed while under the care of one of the best pediatric Crohn’s specialists around, I had plenty of time to do a lot of reading about Crohn’s disease. I happened to come across some interesting medical papers on the use of liquid-only diets in the treatment of adults with Crohn’s disease. By chance those who had been put on elemental liquid formulas, or even more common liquid formulas like Boost or Ensure, had shown significant improvement and often remission after a few months – equivalent to the taking of steroids but without the side effects. So, I asked Wesley’s doctor if this couldn’t be done for Wesley?  He said that while it seemed to work for adults, it had never been done with a young child, and that someone as young as Wesley would probably not be able to tolerate it. He recommended that we start Wesley on powerful “biologic” medications (such as Remicade or Humira) to get his immune system under control so that it would stop attacking his own body.  I knew that his doctor was giving me the best medical advice available, but I also knew that there were side effects to these biologic medications – to include a chance of developing a lethal type of lymphoma that I, as a pathologist, had already diagnosed in young people with Crohn’s disease three times in my career at that point. They had all died within a short time. Although it was a seemingly small risk (one chance in 40,000 per year) I wanted to avoid it if there were any other reasonable treatment options.  So, I asked Wesley’s doctor if he wouldn’t mind writing Wesley a prescription for a 12 week course of Pediasure so that we could try the liquid-only diet.  He agreed to this, I think out of professional courtesy, but warned me that it would be extremely difficult to do and that we would most likely be back in a week or two and have to start the biologic medications at that time.

So, we went home and started Wesley on his new chocolate milk diet. The first day went fine.  After all, what 5-year-old doesn’t dream of getting to have chocolate milk for every meal?!  However, by the second day, Wesley refused to drink any more of the stuff.  I didn’t want to have to put in a naso-gastric tube, so I sat down with him and explained to him, for about an hour, all of the treatment options and their side effects, as best I could to a 5-year-old, and then asked him what he wanted me to do for him?  He looked up at me and said, “I’ll drink the drink”.  And, he did!  The hardheadedness that I’m sure he inherited from my side of the family has its advantages, because, once he set his mind to do it, he was determined, even at 5-years-old, to carry it out till the very end.

Shortly after this, I invited the pastor and elders of my church over to my house to have an anointing service for Wesley. We believe in God and His care for us and wanted to do all we could to align ourselves with what the Bible has outlined for the Christian to do when serious illnesses come along:

Is any one of you sick? He should call the elders of the church to pray over him and anoint him with oil in the name of the Lord. And the prayer offered in faith will restore the one who is sick. The Lord will raise him up. If he has sinned, he will be forgiven. (James 5:14-15)

We held this service not so much to demand healing from God, but to put Wesley into God’s hands so that God could especially bless him and the difficult situation that we were all going through as He saw best – healing or no healing. And, Wesley was not healed at that time.  He was still very sick and continued to be very ill.

Shortly after this, a friend of mine, who happens to be a dermatologist, heard what had happened to Wesley and suggested to me that we consider adding vitamin D supplements to his diet. He explained to me that many of his patient’s with autoimmune skin disorders had responded favorably or had completely recovered once they started taking vitamin D supplements.  Of course, many people where giving me all kinds of unusual advice at this point. I usually dismissed such advice with a smile and a polite “thank you”, but since this particular friend was a dermatologist, I decided to look into it. I found a paper that had been published a few months before that demonstrated a link between vitamin D deficiency and active Crohn’s disease – as well as evidence that those with Crohn’s disease who normalized their vitamin D levels had longer periods of remission. This set a light bulb off in my mind. In medical school I had been taught that certain autoimmune disorders, such as multiple sclerosis for instance, were more common above the 40th parallel. However, we weren’t told why this was true.  Now, it suddenly made sense to me.  There was less sunlight above the 40th parallel! – resulting in less vitamin D!  It also turns out that vitamin D isn’t really a vitamin at all, but a type of hormone that happens to regulate the immune system as well as thousands of other genes in body. It also turns out that up to 40% of Americans are vitamin D deficient (up to 90% in some areas). So, I had Wesley’s vitamin D levels checked and they were low, at around 18 ng/mL. The papers I had read recommended a level of at least 30 ng/mL for those with Crohn’s disease. However, after all I that had read, I thought that a level of around 50 ng/mL would be better for someone with active Crohn’s disease. So, we started giving him 5000 IU of vitamin D per day until his blood levels reached 50 ng/mL, which we then maintained with around 3-4000 IU of vitamin D per day.

As an interesting aside, I’ve also started taking vitamin D supplements myself and I am no longer plagued by the very painful aphthous mouth ulcers I that used to get on a regular basis (also autoimmune related). Also, low vitamin D levels have been linked to an increased risk of various kinds of cancers. For example, a recent study on the risk of breast cancer showed that women with blood levels of vitamin D above 60 ng/mL had one-fifth the risk of breast cancer compared to women with vitamin D levels less than 20 ng/mL (Sharon McDonnell, et. al., June 15, 2018). Vitamin D also helps to reduce the risk of colorectal cancer (Smith-Warner and McCullough, et. al., 2018). Data from studies conducted on three continents that included 5,700 cases of colorectal cancer and 7,100 controls, showed that people who had vitamin D levels below the current guidelines had a 31% increased risk of colorectal cancer while those with vitamin D above the recommended levels had a 22% reduction in risk (stronger link in women than in men). A growing body of research suggests that vitamin D might play some role in the prevention and treatment of type 1 and type 2 diabetes, hypertension, glucose intolerance, multiple sclerosis, and other medical conditions (NIH Fact Sheet, Nov. 9, 2018).

Still, things were not easy at first.  It took Wesley more than 30 minutes to drink each one of the 8 oz drinks, and he had to drink at least six of these per day to keep up his calories.  Most days he was falling behind on his calories.  So, we added some coconut oil to his diet to help increase his caloric intake.  As it turns out, coconut oil is a saturated intermediate chain-length fatty acid that has anti-inflammatory qualities – which was a bonus. Also, after a week or so, I sat down with Wesley and taught him how to guzzle the drinks. I was quite surprised to see him pick up this technique right away so that he could drink one of those 8 oz Pediasure drinks in about 10 seconds or less!

Wesley also learned to pray for himself, which helped my own faith as I witnessed God respond to his little prayers. He was still taking the antibiotic Flagyl at this point to help his colon and abscesses heal.  Of course, it tasted absolutely terrible. So, Wesley prayed one evening that God would make the medicine taste better.  The next day I went to the pharmacy to pick up the new batch of Flagyl and, for some reason, it had been reformulated with a grape flavoring so that it tasted much better than before! Also, during this time, Wesley’s abscesses had been packed with iodinized gauze, which I had to remove daily – small amounts at a time.  This was a very painful process each time – despite the use of topical lidocaine.  So, Wesley prayed one day and told God that he had had enough of the gauze and would He please make it not hurt anymore.  Well, there were two more days left for gauze removal. But, for some reason, when I started removing the gauze that particular day after Wesley prayed, it didn’t hurt him, and there was no more left after I removed the standard daily amount.

And, day after day, over the course of twelve weeks, Wesley started to feel better and better and to gain more and more strength.  At the end of the twelve weeks, we headed back to UC Davis for a checkup, blood work, and another colonoscopy.  Amazingly, the colonoscopy was completely clean!  It looked entirely normal.  Even the biopsies came back entirely normal with no trace of inflammation.  His blood work also showed either normal or almost normal levels for the various enzymes and blood elements.  His doctor was in shock even more than I was. His exact words were, “I’m absolutely astounded!  I never thought it possible…”

Wesley’s doctor presented Wesley’s case to his colleagues and residents and started other children with very early Crohn’s disease on what had helped Wesley – with good success!

Wesley is 9-years-old now and has been in complete remission ever since – not a single relapse!  Those with Crohn’s disease usually suffer two or three relapses each year, but Wesley hasn’t had a single one. He’s growing like a weed and has matched and even exceeded his original growth chart progress before he got sick. Papers have now been published on liquid-only diets for children with Crohn’s disease, all showing good success. Wesley, however, was the first.  He still takes one Pediasure per day even now. At first his doctor asked me why I did this since nothing had been published on this. I told him that since no one knew quite why a liquid-only diet worked for people with Crohn’s disease that I just thought I’d try it as a kind of maintenance therapy – just to see what happened.  And, as it turns out, subsequent studies have shown that the use of some portion of a liquid diet along with solid food, once remission is achieved, is statistically helpful in maintaining remission. Also, Wesley is a vegetarian and avoids dairy since dairy seems to be one of the more common triggers for active Crohn’s disease – for falling out of remission. Also, trans-fats (partially-hydrogenated vegetable oils as well as mono- and diglycerides that are also hydrogenated, but are not required to be listed as “trans-fats”) are highly inflammatory and are completely off the menu for Wesley – and for the rest of us as well!

Still, no one really knows why the liquid diet seems to work for people with Crohn’s disease.  Recently, however, it dawned on me that it might be related to a type of fasting since I recently discovered that fasting has been shown to have similar effects for those with various autoimmune disorders.  As little as a three-day fast (sometimes repeated after a few months) has the ability to “reset” the immune system and relieve or even reverse the symptoms of various autoimmune disorders in most people who suffer from such conditions.

Most importantly, for me anyway, is that I’ve learned to trust God more through these experiences. In retrospect, I now see it as a better miracle that Wesley was not immediately healed when we had him anointed by the elders of the church. Rather, when we specifically and very deliberately placed him in God’s hands for God to do what He saw was best, God gradually, but still miraculously, revealed a better way to deal with Crohn’s disease that helped, not only Wesley, but many other children and adults around the world who suffer with Crohn’s disease and other autoimmune disorders. This wouldn’t have happened if Wesley had been instantly healed of his Crohn’s disease when he was anointed. I now recognize that we were granted an even better miracle than instant healing. Of course, now that I’m on this end of things, I wouldn’t have had it any other way – despite all of the difficulties and pain that we experienced along the way.

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Medical References:

Here’s a few papers on fasting and the resetting of the immune system:
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https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4899145/

Dietary interventions have not been effective in the treatment of multiple sclerosis (MS). Here we show that periodic 3 day cycles of a fasting mimicking diet (FMD) are effective in ameliorating demyelination and symptoms in a murine experimental autoimmune encephalomyelitis (EAE) model. The FMD reduced clinical severity in all mice, and completely reversed symptoms in 20% of the animals. These improvements were associated with increased corticosterone levels and Treg cell number, reduced levels of pro-inflammatory cytokines, TH1 and TH17 cells, and antigen presenting cells (APCs). Moreover, the FMD promoted oligodendrocyte precursor cell regeneration and remyelination in axons in response to both EAE and cuprizone MS models, supporting its effects on both suppression of autoimmunity and remyelination. We also report preliminary data suggesting that a FMD or a chronic ketogenic diet are safe, feasible and potentially effective in the treatment of relapsing remitting multiple sclerosis (RRMS) patients.
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Microbiota of the human body perform fundamental tasks that contribute to normal development, health, and homeostasis and are intimately associated with numerous organ systems, including the gut. Microbes begin gut inhabitance immediately following birth and promote proper gut epithelial construction and function, metabolism and nutrition, and immune system development. Inappropriate immune recognition of self-tissue can lead to autoimmune disease, including conditions such as multiple sclerosis (MS), in which the immune system recognizes and attacks central nervous system tissue. Preclinical studies have demonstrated a requirement of gut microbiota for neuroinflammatory autoimmune disease in animal models, and a growing number of clinical investigations are finding associations between MS status and the composition of the gut microbiota. In this review, we examine current undertakings into better understanding the role of gut bacteria and their phages in MS development, review associations of the gut microbiota makeup and MS, and discuss potential mechanisms by which the gut microbiota may be manipulated for therapeutic benefit.
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Short term fasting seems to have made a resurgence into popularity in recent years, with intermittent fasting re-gaining fame for more than just weight loss benefits. So what happens when we move beyond the intermittent to prolonged fasting a couple of times a week? There is research revealing that fasting twice a week could significantly lower the risk of developing both Parkinson’s and Alzheimer’s disease [1]. But new research has revealed another benefit of fasting or diets that mimic it. It appears that it can trigger stem cell regeneration to help reboot damaged immunesystems.
The research revealed that “fasting for as little as three days can regenerate the entire immune system, even in the elderly [2].” It has applications for people whose immune systems have been decimated by chemotherapy, undermined by diseases like Multiple Sclerosis, or simply declined with age.

Still, they have turned up some very interesting findings in their quest to understand how the body reacts to fasting or fast-mimicking diet protocols.

    • One study looked at mice with autoimmune diseases put through a three day fast every seven days. It showed increased levels of corticosterone (a steroid hormone), a reduction in inflammation-causing cytokines, and improvements in white blood ‘t cells’ responsible for immunity [5].
    • They also found that the fasting-mimicking diet protocol promoted the regeneration of myelin that had been damaged by autoimmunity [5].
    • The fasting-mimicking diet also resulted in improved metabolism and cognitive function, decreased bone loss and cancer incidence, and extended longevity [6].
    • They found that, in humans, the fasting mimicking diet used in the prescribed regularity and length, reduced multiple risk factors of aging [6].
    • Cycles of prolonged fasting reduced damage in bone marrow stem and progenitor cells, and protect against chemotoxicity [7].
  • Prolonged fasting cycles regulated stem cell populations independently of chemotherapy and helped reverse immunosenescence, and had significant impacts on hematopoietic regeneration [7].
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Furthermore, fasting leads to significant reductions in levels of leptin, a pro-inflammatory adipokine that is elevated in rheumatoid arthritis, systemic lupus erythematosus, type 1 diabetes, autoimmune hepatitis, multiple sclerosis, Behcet’s disease, psoriasis, and ulcerative colitis (25, 26). This has the effect of up-regulating CD4+ CD25+ Foxp3+ regulatory T cells, the subset of immune cells which induce peripheral immune tolerance, are depleted in autoimmune disease, and are inhibited by leptin (26). Fasting also improves ketone production, insulin sensitivity, hepatic glycogenolysis, adipose tissue lipolysis, and anabolic activity in muscle, all of which promote metabolic correction (1, 2). A review of the literature also reveals that fasting improves many other metabolic biomarkers, such as glucose, lipids, leptin, and adiponectin (Patterson et al., 2015). Increases in adiponectin, which occur with fasting, are favorable since levels of this anti-inflammatory fat tissue-derived adipokine are compromised in multiple sclerosis, psoriasis, and Sjogren’s (25).
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Exclusive Enteral Nutrition and Crohn’s Disease:
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http://www.hindawi.com/journals/grp/2013/482108/

“Corticosteroids are considered the first line treatment for active CD. They have been shown to induce remission in most patients when administered for a period of 4–6 weeks [42]. There have been several studies demonstrating equivalent efficacy of EEN in inducing remission in active CD.Ruuska et al. [43] conducted a randomised control trial comparing the efficacy of whole protein based formula with corticosteroids in 19 children over a period of 11 weeks. The children treated with EEN had a longer relapse free duration and better nutritional status when compared to children in the corticosteroid group. This study also demonstrated the effectiveness of EEN in the treatment of children suffering from a relapse.”

 
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Here’s a few on Vitamin D and autoimmune disorders:
 
Vitamin D and MS:
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A study conducted by researchers at the University of Oxford and another conducted at the New Jersey Medical School have suggested that maintaining adequate levels of vitamin D may have a protective effect and lower the risk of developing multiple sclerosis (MS).
Another study conducted at Maastricht University in the Netherlands and others suggest that for people who already have MS, vitamin D may lessen the frequency and severity of their symptoms.
The link between vitamin D and MS is strengthened by the association between sunlight and the risk of MS. The farther away from the equator a person lives, the higher the risk of MS.
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An array of new data indicates that proper supplementation with low-cost vitamin D can induce a meaningful beneficial effect on multiple sclerosis patients.
According to the latest research, vitamin D offers hope for those suffering from multiple sclerosis. Ample data show that low levels of vitamin D are associated with an increased risk of developing MS,4-7 and the vitamin has been shown to be effective in patients by reducing MS-caused inflammation. Studies show that having adequate levels of vitamin D can not only decrease the risk of developing MS, but can also delay its progression.
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Researchers checked the symptoms of people in an early stage of MS. They found that after 5 years, those with more vitamin D in their blood had fewer problems.
Studies show that children who get a lot of sunlight, which is one way to get vitamin D, are less likely to get the disease when they grow up.
Some research also shows that people who live away from the equator, where there’s less sunlight, have a higher rate of MS.
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Patients with multiple sclerosis (MS) who took high doses of cholecalciferol (vitamin D3) had increased blood levels of 25-hydroxyvitamin D levels [25(OH)D] to those proposed to be sufficient in MS and showed promising immunologic changes, in a new study.
The authors explain that optimal levels of serum 25(OH)D in MS are currently unclear, but it has been proposed that levels between 40 and 60 ng/mL may be the best target for this population, which such levels being achieved with the high dose of cholecalciferol given in this study, but not with the low dose.
In terms of immunologic effects, patients taking the high dose of cholecalciferol showed a reduction in the proportion of interleukin (IL)-17 CD4+ T cells, CD161 CD4+ T cells, and effector memory CD4+ T cells, which are believed to be major contributors to the immunopathogenesis of MS. The high-dose group also showed a concomitant increase in the proportion of central memory CD4+ T cells and naive CD4+ T cells. None of these effects were observed in the low-dose group.
 
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 Vitman D and Crohn’s Disease:
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“In a double-blind randomised placebo-controlled study, the authors assigned 27 CD patients in remission to 2000 IU/day vitamin D supplementation or placebo for 3 months. They found, that patients treated with the supplementation were more likely to maintain their intestinal permeability, whereas this deteriorated in the placebo group. Increased intestinal permeability is considered a measure of gut leakiness, which is shown to predict and precede clinical relapse in CD. In addition, patients with the highest blood levels of vitamin D had signs of reduced inflammation (measured by C-reactive protein and antimicrobial peptides), and these patients also reported better quality of life. The authors conclude: “This is the first reporting of effects of vitamin D supplementation on intestinal permeability and antimicrobial peptide measures in a CD cohort.”

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See also:

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https://www.vitamindcouncil.org/blog/rct-finds-vitamind-may-be-an-effective-treatment-for-crohns-disease/

The inflammation that results from CD often spreads deep into the layers of affected bowel tissue. Not only can CD be painful and debilitating, but it may also lead to life-threatening complications.

There is no known cure for CD, but various therapies can reduce its signs and symptoms. In some cases, treatment can even lead to long-term remission.

The incidence of CD is increasing all around the world. In Europe, the incidence of inflammatory bowel disease has increased from 1.0 per 100,000 person-years in 1962 to 6.3 per 100,000 person-years in 2010.

CD is more common in countries far from the equator, but season-of-birth and seasonality studies have been mixed. A number of studies have found lower 25(OH)D levels in patients with CD compared to controls. Studies have also found 25(OH)D levels are associated with disease severity.

In 2011, a poster at the Washington DC American College of Gastroenterology meeting, presented the findings from

Dustin Boothe, Harrison Lakehomer, Vinita Jacob, Ellen Scherl, and Brian Bosworth, of Weill Cornell Medical College, New York, NY, that 10,000 IU/day was superior to 1,000 IU/day in reducing disease severity.

In 2013, we wrote about an open label trial that showed approximately 5,000 IU/day of vitamin D significantly reduced disease severity and increased quality of life in CD.

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Open-label pilot trial: Vitamin D helps manage Crohn’s

Now Maria O’Sullivan and colleagues, Department of Clinical Medicine, Trinity Centre for Health Sciences, St. James’s Hospital, Dublin, Ireland has recently treated 27 patients with CD in a randomized controlled trial. The trial compared treatment with 2,000 IU/day to placebo treated patients.

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Raftery et al. Effects of vitamin D supplementation on intestinal permeability, cathelicidin and disease markers in Crohn’s disease: Results from a randomised double-blind placebo-controlled study. United European Gastroenterology Journal June 2015 vol. 3 no. 3 294-302.

At 3 months, mean 25(OH)D levels in the treatment group were 36 ng/ml compared to the placebo group of 16 ng/ml (p< 0.001). In the treatment group, 4 participants did not obtain serum 25(OH)D concentrations of 30 ng/ml at 3 months. All of those in the placebo group had 25(OH)D concentrations < 30 ng/ml at 3 months.

When analyzed according to 25(OH)D concentrations achieved at 3 months, the subjects whose levels were > 30 ng/ml had significantly lower gastro-duodenal permeability (p = 0.030), better quality of life (p < .03), lower CRP levels (p > 0.02), higher concentrations of cathelicidin, (p < 0.001) and non-significantly better disease severity markers (p= .08). Cathelicidin is an antimicrobial peptide which aids in fighting bacteria. Interestingly, the difference in cathelicidin concentrations were more pronounced when > 40 ng/ml was used as a cut-off point; this may support arguments that 25(OH)D levels need to reach a level of > 40 ng/ml to exert maximum immune effects.

Our position is that patients with CD should get enough sunshine or take enough vitamin D to have“natural” 25(OH)D levels (> 40 ng/ml). In many people, this will require 10,000 IU/day.

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