Crohn’s Disease and IBD Remission with Amino Acid Therapy

If you are suffering with Inflammatory Bowel Disease (IBD) including Crohn’s disease (CD), ulcerative colitis (UC), it is possible that you could achieve remission by supplementing with amino acids. CD and UC fall under the IBD umbrella term, so from here on out I will be referring to all of them simply as “IBD.”

There is no known cure for inflammatory bowel disease, and traditional methods of symptom management are inadequate.  Many various alternative methods are so individualized that studying them is near impossible because what works well for one patient often does not work for others.  This presents a unique challenge for researchers, but certainly research is underway and much of it is promising.  The current pharmaceutical treatments for IBD are corticosteroids, aminosalicylates, immunosuppressants, and TNF blocking agents or combinations of these (Mayo Foundation for Medical Education and Research (MFMER) (2018). These drugs are not without side effects; and remission rates (onset of remission as well as maintenance of remission) are disappointing at less than 50% in most cases.

In a systematic review of current therapies for IBD, Peyrin‐Biroulet and Lémann (2011) stated that current therapies simply fall very short of what patients need, and they have only a modest impact on surgical rates, which further indicates many patients are simply not obtaining remission.

Even patients who receive last resort treatment with TNF blockers (such as Remicade for Crohn’s disease) are likely to require intestinal resection (about one-fifth of CD and UC patients) (Peyrin‐Biroulet & Lémann, 2011). And while surgery often leads to clinical remission of IBD, most people end up eventually relapsing (Fedorak, Penner, & Tandon, 2017).  We don’t know exactly what causes IBD–we have theories (and current treatments are typically based on those theories). Well, what if those theories are wrong?

Now that we have identified that the current treatments are essentially no better than a coin toss, their side effects only add new problems, and surgically removing part of the intestine is most certainly not a cure-all, what alternatives are available to IBD patients? There is very compelling evidence that amino acid therapy can lead to remission.

So which amino acids may help? Well, in one case study it appears that a combination of the serotonin and dopamine precursors L-tyrosine, L-cystiene, 5-HTP, and L-Dopa (5-HTP and L-Dopa are NOT amino acids) as well as their cofactors (needed for proper metabolism/absorption) lead to profound resolution of symptoms and remission after only six weeks of therapy followed by remission and maintenance of remission (Hinz, Stein, & Uncini, 2010). Here is the dosage table from this study that was done on a man who suffered with Crohn’s symptoms for 22 years with no relief from the traditional treatment methods we discussed earlier. The authors Hinz, Stein, and Uncini (2010) note that this protocol has been used successfully for a number of patients.

Take care to read the note in the table. Cofactors are essential.  (I will be writing a specific post about which cofactors are needed for each amino acid, so stay tuned.) The protocol includes urine analysis of neurotransmitters to identify whether or not they were obtaining a balance between serotonin and dopamine with the amino acid supplementation. I know what you are thinking: “Wait a minute, isn’t serotonin just in my brain?” Nope. Serotonin actually plays a huge role in gastrointestinal motility and secretions. Far more research needs to be done on what is now being called the Gut-Brain Axis.

“Scientific evidence strongly suggests that serotonin – or 5HT – is one of the most important signalling molecules involved in the peristaltic reflex – and that alterations in serotonin signalling may be responsible for IBS symptoms. Ninety-five percent of the serotonin found in the body resides in the gut.” – Gastrointestinal Society (2018)

Other Amino Acids that Support Gastrointestinal Health (Hu, Liu, & Wang, 2017) (follow me for future posts that explain each one in depth).

L-Glutamine (the most abundant free amino acid in the human body)

L-Arginine (our body’s demands for this are highest in diseased states)

L-Glutamate (our nervous system’s most abundant excitatory neurotransmitter)

Sulfur-Containing Amino Acids (Methionine and Cysteine)

N-acetylcysteine (NAC): precursor of cysteine and glutathione (our body’s master antioxidant)

L-Threonine (a crucial building block for many other conditionally essential aminos)

Tryptophan (for the same reasons 5HTP seems to work so well, and so much more)

L-Glycine (the reason bone broth is a superfood).

L-Histidine (a powerful free radical scavenger)

One final note:

Diet and lifestyle modifications are your first step to healing. I believe the paleo diet or the ketogenic diet are ideal. When you are ready to make that change (which should be today), Primal Blueprint by Mark Sisson is an excellent resource. He also has a blog called Mark’s Daily Apple. Healing from IBD is a process. Even if remission is achieved with amino acid therapy, it takes time to heal the damage done by IBD. If you need some direction on how to heal issues like hemorrhoids, anal fissures, intestinal strictures, bowel obstructions, anal stenosis, and many others you can check out Listen to Your Gut.

If you have any questions or comments, or if you feel it is necessary to correct something that you read here, feel free to do so below. I appreciate any and all of your contributions. If you think this post could help a friend, share it. You might change their life.

Legal Disclaimer: The information, including but not limited to, text, graphics, images, website links and other material contained on this website are for informational purposes only. The purpose of this website is to promote broad consumer understanding and knowledge of various health topics, as well as share personal opinions and experiences. It is not intended to be a substitute for professional medical advice, diagnosis or treatment. Always seek the advice of your physician or other qualified health care provider with any questions you may have regarding a medical condition or treatment and before undertaking a new health care regimen, and never disregard professional medical advice or delay in seeking it because of something you have read on this website.

References

Fedorak, R., Penner, R., & Tandon, P. (2017). Management of Crohn disease after surgical resection. Retrieved from https://www.uptodate.com/contents/management-of-crohn-disease-after-surgical-resection

Gastrointestinal Society. (2018). IBS and serotonin. Retrieved from https://www.badgut.org/information-centre/a-z-digestive-topics/ibs-and-serotonin/

Hinz, M., Stein, A., & Uncini, T. (2010). Amino acid-responsive Crohn’s disease: a case study. Retrieved from https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3108661/

Hu, C., Liu, Y., & Wang, X. (2017). Therapeutic potential of amino acids in inflammatory bowel disease. Retrieved from https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5622680/

Mayo Foundation for Medical Education and Research. (2018). Inflammatory Bowel Disease. Retrieved from https://www.mayoclinic.org/diseases-conditions/inflammatory-bowel-disease/diagnosis-treatment/drc-20353320

Peyrin‐Biroulet, L. & Lémann, M. (2011). Review article: remission rates achievable by current therapies for inflammatory bowel disease. Retrieved from https://onlinelibrary.wiley.com/doi/full/10.1111/j.1365-2036.2011.04599.x

Chronic Pain: What are Enkephalinase Inhibitors?

“5.3 million adults (11.2 percent) experience chronic pain—that is, they had pain every day for the preceding 3 months. Nearly 40 million adults (17.6 percent) experience severe levels of pain.”  – U.S. Department of Health and Human Services, 2015

Those numbers are horrific, and they are most likely a gross underestimation.  Chronic pain can be debilitating, and is the leading cause of disability in America.  If you are reading this and sitting there in pain, hang in there.  Keep reading.

Before we get into the amino acids, I am going to mention that it is monumentally important that chronic pain sufferers make sure they are eating a healthy diet filled with nutrient rich and anti-inflammatory foods — and not just on Sundays.  Garbage in isn’t garbage out, garbage in is inflammation, illness and pain. Start there. I personally do my best to maintain a cross between paleo and ketogenic dietary lifestyle. It has worked well my family.  Mark Sisson’s Primal Blueprint is an excellent resource for people who want to jump into the paleo way.

So, what the heck is enkephalinase?  You could skip this entire paragraph, but I am a huge proponent of people understanding how something works before they decide to take it, so I encourage you to do your best with this complicated information.  You will need to understand this first to understand how and why the amino acid d-phenylalanine works to alleviate chronic pain. Enkephalinases are enzymes that break down our endogenous enkephalin opioid peptides.  Huh? Ok, let’s break it down a bit. Enkephalins are essentially one of the natural opioids found in the human body, and their receptor sites are opioid receptors. Opioid peptides are short chains of amino acids that actually bind to those opioid receptors on the sensory nerve endings, thereby inhibiting painful sensations.  This means that enkephalins are your natural morphine, except better.  They have an affinity for two (out of the three) main opioid receptors: the mu-opioid receptors (MORs) and the delta-opioid receptors (DORs).   

This is important because the affinity (definition of affinity here is the enkephalin’s ability to bind to the intended target site) of enkephalins for MORs is nearly identical to morphine, whereas their affinity for DORs is about ten times higher (Fournié-Zaluski, Roques, & Wurm, 2012).

That’s right, I said TEN TIMES HIGHER than morphine.  So basically, enkephalinases are the enzymes that break down enkephalins, preventing the human body from benefiting from one of its primary internal pain relief systems that are potentially stronger than drugs like morphine (which of course has many undesirable side effects, as do other narcotics).  If you need further explanation, feel free to comment below and I will do my best to clarify for you. I try to do my best to be a good science communicator. It’s not easy, but sometimes having the right question helps me provide a clear answer, so feel free to help me out.

Now that we understand enkephalinases, we can look further into how d-phenylalanine works.  D-phenylalanine is an enkephalinase enzyme inhibitor.  Therefore, it helps you to KEEP your enkephalins (those feel-good natural opioids) working in your brain and spinal cord where those pesky pain impulses are transmitted.  You might be concerned that enkephalinase inhibitors might cause all the same side effects of exogenous opioids like morphine, but studies show that their major advantage is that they deliver pain relief that is better than morphine, but without any of the opioid side effects (Ghosh, R., Kadum, V., & Thanawala, V., 2008).  

There are many drugs being developed by pharmaceutical companies that are enkephalinase inhibitors as well that are being termed “DENKIs.” For example, in a study on mice, the enkephalinase inhibitor drug PL265 was highly effective for cancer related bone pain (they also studied its use in combination with drugs that act on cannabinoid receptors and found that the results were even better) (Baamonde et al., 2017). You can follow more here: http://www.pharmaleads.com/latest-publication/.  

The bottom line is that enkephalinase inhibitors work so well that it is only a matter of time before the painkiller industry capitalizes on it.  After all, about $300 billion per year is spent on painkillers, and that’s just here in America.

Now, obviously, chronic pain comes in all shapes and sizes.  There are different types of pain. No one person’s pain experience is the same as another’s.  And chronic pain can be caused by a variety of issues. Further, chronic pain leads to a multitude of other issues affecting both mental and physical health.  Even if d-phenylalanine works for you, it is essential not to ignore other problems that may have resulted from suffering for so long. And of course there is the possibility that it will not work for you at all.  There could be issues with absorption, other hormone issues, contraindication medical history, medication interactions, etc. For instance, people who have been diagnosed with Phenylketonuria (PKU) should never, ever take d-phenylalanine.  That is why I always advise people to speak with their health care provider before taking any supplement or adding any form of therapy into their health regimen. There are many brands of d-phenylalanine (DPA) available for purchase online.  One brand I generally trust is Drs Best. We use many of their supplements in our home.

I hope this article helped you.  If DPA does not work for you, keep your eyes open for the advancements in other enkephalinase inhibitor drugs.   Another option for natural pain relief is CBD oil. I will be posting on CBD oil in the future.

If you have any questions or comments, or if you feel it is necessary to correct something that you read here, feel free to do so below.  I appreciate any and all of your contributions. If you think this post could help a friend, share it. You might change their life.

Legal Disclaimer: The information, including but not limited to, text, graphics, images, website links and other material contained on this website are for informational purposes only. The purpose of this website is to promote broad consumer understanding and knowledge of various health topics, as well as share personal opinions and experiences. It is not intended to be a substitute for professional medical advice, diagnosis or treatment. Always seek the advice of your physician or other qualified health care provider with any questions you may have regarding a medical condition or treatment and before undertaking a new health care regimen, and never disregard professional medical advice or delay in seeking it because of something you have read on this website.

References

Baamonde, A., González-Rodríguez, S., Fournié-Zaluski, M., Lastraa, A., Menéndez, L., Ouimet, T., Poras, H., & Roques, B. (2017). Synergistic combinations of the dual enkephalinase inhibitor PL265 given orally with various analgesic compounds acting on different targets, in a murine model of cancer-induced bone pain. Scandinavian Journal of Pain. Retrieved from https://www.degruyter.com/downloadpdf/j/sjpain.2017.14.issue-1/j.sjpain.2016.09.011/j.sjpain.2016.09.011.pdf

Fournié-Zaluski, M., Roques, B., & Wurm, M. (2012). Inhibiting the breakdown of endogenous opioids and cannabinoids to alleviate pain. Nature Reviews Drug Discovery, 11, 292-310. Retrieved from https://public.weconext.eu/speed-sciences-2014/fragment_003/NRDD_2012.pdf

Ghosh, R., Kadum, V., & Thanawala, V. (2008).
Enkephalinase inhibitors: potential agents for the management of pain. Retrieved from https://www.ncbi.nlm.nih.gov/pubmed/18855623

U.S. Department of Health and Human Services. (2015). NIH Analysis Shows Americans are in Pain.  Retrieved from https://nccih.nih.gov/news/press/08112015

ADHD: An Alternative Approach Using Amino Acids

Attention Deficit Hyperactivity Disorder (ADHD) is considered a neurodevelopmental disorder. Currently, the treatment for this disorder is primarily with various forms of the central nervous system stimulants methylphenidate and amphetamine. There is very little research on the long term effects of these drugs, and what we know from the research that does exist is not encouraging.

For instance, we know that long-term use of stimulants, even as prescribed by a physician, can lead to tolerance and the need for higher and more frequent doses to get the desired effect (National Institute on Drug Abuse, 2018).

There are some nonstimulants that were approved for use with children who do not respond well to stimulants (FDA, 2017). The nonstimulants include Strattera (atomoxetine), Intuniv (guanfacine), and Kapvay (clonidine).  These were approved for this use quite recently, so the effects of long term use has yet to be determined (FDA, 2017). Atomoxetine was approved in 2003; Guanfacine was approved in 2009; and Clonidine was approved only in 2010.

Unfortunately, people are needing to choose between the ADHD symptoms and the often equally cumbersome side effects of nonstimulants. The use of nonstimulants is not nearly as common as the use of stimulants, so this post is going to be focusing on stimulant use. The amino acid we will be focusing on here is L-Tryptophan. L-tryptophan is a precursor to serotonin, which means it is nutritionally essential for the production of serotonin.

There are various studies underway which are trying to determine the “cause” of ADHD. I personally don’t believe there is one specific cause for all who are diagnosed with ADHD, and it is also widely accepted that regardless of the diagnosis, there are many factors that may exacerbate ADHD symptoms (diet, environmental exposures, etc). The very fact that stimulants work for many children but not ALL of them is at least one good indicator that the root cause of ADHD may not always be exactly the same from one child to the next. We are all unique individuals, after all.

Okay so you may be asking, “How does a stimulant work to help calm down and focus someone? A stimulant should stimulate right?.” Well, yes and no.

It should be noted that the mode of action of stimulants in ADHD is not well understood. Just as there are various theories for the cause of ADHD, there are also various theories on how drugs work to affect ADHD. This means that stimulants are given to ADHD patients, and they work, but we don’t exactly know how they work. One theory is that they prevent the reuptake of dopamine and norepinephrine, which increases the activity of those neurotransmitters in a part of the brain called the prefrontal cortex. The prefrontal cortex is responsible for impulse control, decision making, moderating the way we behave in social situations, and complex planning. Another theory that I find interesting is the hypothesis that rather than an issue with the quantity of available dopamine and norepinephrine, there is some kind of disturbance in the blood brain barrier that does not allow enough of the amino acid tryptophan to be transported across it.  Tryptophan deficiency within the brain would not necessarily appear in typical blood work.  To clarify, a person may have plenty of tryptophan circulating in their blood, but if the blood brain barrier won’t let enough of it in, there is a brain deficiency (and there is not really a safe way to study brain deficiencies). And if there is a brain deficiency of tryptophan it can be assumed that there is also a serotonin deficiency since the brain utilizes tryptophan to create serotonin.

Wait, weren’t we talking about dopamine? Yes, indeed we were. Hang with me here. Serotonin and dopamine essentially work together–in a way, they are constantly balancing each other out.

The serotonergic system directly influences the dopamine system, and a chronic deficiency of serotonin at the point where brain neurotransmitters allow communication between two neurons (called a synapse) is known to trigger symptoms of ADHD (Banerjee & Nandagopal, 2015).

So a serotonin deficiency could negatively impact dopamine levels and activity in the brain. This may be why L-tryptophan supplementation significantly alleviates ADHD symptoms (Banerjee & Nandagopal, 2015). To me, it makes sense that increasing the available circulating tryptophan via supplementation or diet would help more of it move across the blood brain barrier.

This is further supported by the prevalence of ADHD among alcoholics, as the consumption of alcohol increases brain concentrations of serotonin (WebMD, 2018).

Perhaps ADHD patients are more prone to alcoholism partly because they are deficient in serotonin.  There is a lot of literature (in books, journals, and online medical resources) that suggests supplementation with tryptophan helps to alleviate the symptoms of ADHD. I have also read many anecdotal stories from adults diagnosed with ADHD and from parents with children who have ADHD who found that tryptophan or 5HTP supplementation helped tremendously.  5HTP is NOT an amino acid, but it is known to increase serotonin levels. Although this blog will primarily focus on amino acids, I will post more on 5HTP in the future because it seems to be commonly used in combination with amino acids for various health issues.

Finally, L-tryptophan may not work for everyone with ADHD.  Remember, each individual in unique.  There are many other alternative approaches, and I encourage you to do your research before any final decisions are made.

If you do decide to give your child a tryptophan supplement (which is found in animal and plant proteins that we eat every day), or if you decide to take it yourself, it should be under the care and supervision of your physician.

There is a brand called Lidtke that makes a chewable tryptophan tablet. I have tasted it, and can tell you that it smells like pancakes and tastes like maple syrup.  In general, it is best to take a pure form of L-tryptophan such as this powder version from NutraBio. Pure L-tryptophan doesn’t taste wonderful, but its not terrible either. It is also available in pill form but I always try to take the powdered form of amino acids because I don’t necessarily want to ingest any unnecessary additives or the capsule itself.

Another amino acid that may help with ADHD is L-Tyrosine, especially when used in combination with the 5HTP (from the seeds of an African plant known as Griffonia simplicifolia) but that requires a different post for more detailed information (which I will be writing soon enough).

If you have any questions or comments, or if you feel it is necessary to correct something that you read here, feel free to do so below. I appreciate any and all of your contributions. If you think this post could help a friend, share it. You just might change their life.

Related posts

Long Term Effects of ADHD Medications

Legal Disclaimer: The information, including but not limited to, text, graphics, images, website links and other material contained on this website are for informational purposes only. The purpose of this website is to promote broad consumer understanding and knowledge of various health topics, as well as share personal opinions and experiences. It is not intended to be a substitute for professional medical advice, diagnosis or treatment. Always seek the advice of your physician or other qualified health care provider with any questions you may have regarding a medical condition or treatment and before undertaking a new health care regimen, and never disregard professional medical advice or delay in seeking it because of something you have read on this website.

References

Ahlin, A., Bejerkenstedt, L., Fernell, E., … (2011). Altered tryptophan and alanine transport in fibroblasts from boys with attention-deficit/hyperactivity disorder (ADHD): an in vitro study. Retrieved from https://behavioralandbrainfunctions.biomedcentral.com/articles/10.1186/1744-9081-7-40

Banjeree, E. and Nandagopal, K. (2015). Does serotonin deficit mediate susceptibility to ADHD? Retrieved from https://www.ncbi.nlm.nih.gov/pubmed/25684070

National Institute on Drug Abuse. (2018). Prescription Stimulants. Retrieved from https://www.drugabuse.gov/publications/drugfacts/prescription-stimulants

U.S. Food and Drug Administration. (2017). Dealing with ADHD: What You Need to Know. Retrieved from https://www.fda.gov/ForConsumers/ConsumerUpdates/ucm269188.htm

WebMD. (2018). ADHD and Substance Abuse. Retrieved from https://www.webmd.com/add-adhd/adhd-and-substance-abuse-is-there-a-link#1