Low dose Naltrexone (?)

[LA18]

Has anyone had experience with low dose Naltrexone? I’m having a gastrointestinal crisis (severe small intestine bacterial overgrowth) and my new gastro, who specializes in this condition, feels that I could really benefit from taking this drug. But I’m wary, because of my e4/4 status, about taking anything that crosses the blood brain barrier. I’ve searched the literature but haven’t found anything on naltrexone and ApoE4 and was wondering if there’s something I’m missing. At this point I’m leaning toward trying it, because I’m out of other options and eating has become difficult. Presumably the problem is due to a structural abnormality and/or motility issue. Thus, dietary modification has not been effective. Any thoughts on this would be much appreciated!

[Stavia]

I cant see any pharmacological mechanism that could be a specific dangerous apoe4 issue. As it is specifically an opioid receptor drug we currently don't IMO have a known link to our particular issues.
My personal rule of thumb is that if a medication makes me feel spacey or drugged its not a good idea long term.
I can't see any harm in doing a 3 month trial.

[Julie G]

(((LAC))) I’m so sorry you’re dealing with this, my friend. I’ve also struggled with GI dysmotility- as have many others here. From what I’ve been able to glean, this is a relatively new (and promising) usage for naltrexone, right? While acknowledging the success, I have concerns about YOU using it, knowing what I do about your presentation and neurological susceptibility. Check out the link below:

Low Dose Naltrexone: Side Effects and Efficacy in Gastrointestinal Disorders
http://www.gidoctor.net/client_files/fi ... orders.pdf

Naltrexone is a water soluble compound which crosses the blood brain barrier, and this increases the potential for neurologic side effects. Reported adverse effects of standard dose naltrexone include anxiety, nervousness, confusion, drowsiness, hallucinations, skin crawling, blurred vision, muscle or joint pain, vomiting, diarrhea, stomach pain, liver disease, and skin rash.

From a survey of patients using naltrexone for GI motility:

In the patients who returned the survey, 47/121 (38.8%) had no side effects. Of the 74/121 (61.2%) patients who had side effects, 58 had one or more neurological complaints, and 32 had one or more GI side effects. [Emphasis mine.]

I suspect there may be safer approaches for you. As I recall, you’ve fairly recently had GI surgery. Is your motility worsened since then? I ask, as I experienced the same following my gallbladder removal. My motility completely shut down for about 6 months. I became VERY weak and was repeatedly hospitalized. Are you actively treating the SIBO with standard antibiotics? Can you tolerate probiotics or plain kefir? (Good to use concurrently with the antibiotics.) Are you currently using a GI prokinetic? All of these steps will address the problem at a gut level and not involve the BBB. Another remedy/protection you can immediately employ is drinking bone broth regularly as you heal. That will help address the permeability issues caused by the SIBO/dysmotilty. I’m happy to share what finally helped me if you think it will help. I’m sending lots of love and healing energy your way.

[Kim]

I have thought about taking LDN as a so called "tweak." I may be more "adventurous" than most people with regard to self-hacking. But, I have done a ton of research on LDN and it is really cutting edge stuff. I have been wanting to bring up the topic of LDN in the context of microglial activation and Alzheimer's Disease, but there is so much type out there about LDN I have been hesitant. But, here goes - just throwing it out there.

LDN is a Toll Like Receptor 4 ("TLR4") antagonist. Research has shown that in the inflammatory model of Alzheimer's Disease there is an upregulation of TLR4. Therefore, I thought that something like LDN could hypothetically help. I became interested in TLRs because I have a TLR4 mutation referred to as ASP299GLY and I wanted to determine if there is a connection with neurodegeneration.

Here is an article about TLR4 and Alzheimer's Disease. http://www.ncbi.nlm.nih.gov/pubmed/17982277
Here is an article about neuroinflammation and LDN. http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3962576/
Here is an article about a TLR4 mutation and Alzheimer's Disease. http://www.researchgate.net/publication ... 's_disease

Kim

[LA18]

Stavia, thank you for weighing in on this. I’ve just been catching up on my reading here. I’m so sorry for your loss.

Juliegee, yes, I had a fundoplication in May of 2014 after years of uncontrollable reflux due to a structural problem. I’ve had documented SIBO since 2006, but the symptoms did get much worse after the surgery (and the gallstone I had this past summer). I’ve taken the standard drugs, and they work, but the effect doesn’t last. It’s so severe that it affects my breathing and I can’t eat anything fermentable. Right now I’m living on jasmine rice (as a diabetic, so small quantities with insulin- to avoid metabolic acidosis), some leafy greens, and salmon.

What’s interesting is that some of my other problems – interstitial cystitis and rosacea, which are also flaring- have been linked to SIBO. I suspect I’ve had it much of my life, at least at a base level, and now, post-surgery and gallbladder problem, it’s just ramped up to the point where it’s intolerable.

I hear your concerns given my situation and appreciate the feedback. I will start a prokinetic drug soon (waiting for my prescription), which should help. I’m not thrilled about taking that either, but this one (prucalopride) has a decent side effect profile, and I’ll be on an extremely low dose.

On complicating factor is that I’m an HLA-B27 carrier. This is essentially an autoimmunity gene, and it’s been associated with SIBO, inflammatory bowel and, most significantly ankylosing spondylitis, which I do not have (gratefully, my father does). I think this is one reason why the gastro feels that the LDN could be helpful. But, I agree, it seems pretty risky given my vulnerabilities.

I would definitely be interested in more information about how you healed your gut. You are completely grain free, correct? I’ve tried kefir, which I love, but I really can’t tolerate dairy. It makes me feel worse than gluten, which I also avoid. Bone broth I can take. Did you have this daily?

Kim, thanks for posting those articles. I can see the potential benefits in my situation- I know inflammation is an issue for me – but I’m so sensitive to everything, I’m worried that introducing something like this will trigger some unwanted outcome. My body does have a tendency to do strange things. I think I’ll start with the prokinetic first, see how it goes, and then reassess.

[Gilgamesh]

LAC, sorry to hear about your crisis. Standard dose naltrexone can have some side effects, as J noted. Low-dose is of course generally more well tolerated.

I've actually been intrigued by the research into LDN and CFIDS.

http://www.cortjohnson.org/treating-chr ... e-syndrom/

GB

[Julie G]

Kim & G, VERY interesting to see the other potential uses for Naltrexone. I'll look forward to learning more. It's worth noting that the neurological side effects I posted were on the very low doses. That gives me pause.

Apologies in advance for a ridiculously long post. My family & I have been through the wringer with GI dysmotility and I'd love to help prevent anyone from making the mistakes we did by not being aware of our E4 status.

LAC, thanks for refreshing my memory on your GI issues. Me too on the interstitial cystitis and rosacea. Perhaps not surprisingly, mast cells are also strongly correlated with both...and the dysmotility as well. I see lots of overlap between mast cell and gut issues with huge implications for neurological health.

Following my GI surgery, my gut completely shut down. My lifelong IBS-D turned into intractable C. I experienced severe nausea every time I tried to eat. I grew very thin and weak. My BP became very low during this period. Interestingly, rice was the only thing I could tolerate during that period as well. Often, I couldn't even eat that. I didn't use bone broth back then...didn't know about it.

What ultimately "rescued" me was very small doses of both my son's GI prokinetic (Ery-Ped) and his florinef- prescribed for his neurally mediated hypotension/autonomic dysfunction. At 13 y/o, he was DXed with a connective tissue disorder that predisposes him to the autonomic dysfunction and small bowel dysmotility. Recurrent SIBOs were a part of his presentation- treated with Flagyll. CFIDS was the umbrella term his Hopkins docs gave his condition. They still manage his care. I'm generally a healthier version of him, but have had aspects of his illness throughout my life.

Before that, I tried taking Zelnorm (might be similar to Prucaloprode) with little benefit and greatly worsened hypoglycemia. I know you've also had major BG problems...and you're now DXed with diabetes? You need to be very careful with GI motility meds. They can cause huge BG drops. I had a major BG crash on Zelnorm involving paramedics.

GI prokinetic have traditionally had awful side effects- including severe neurological implications. My son was on Reglan until we realized he'd developed a tremor and was bouncing off the walls. The tremor persists to this day. Prucaloprode does look better, but I still see neurological reports like the one below. It might be worth while to try to get your hands on full-text to see if the mechanism of action described could have implications for your E4 status.

Neurological and psychiatric adverse events with prucalopride: case report and possible mechanisms.
http://www.ncbi.nlm.nih.gov/pubmed/23889005

FWIW, Ery-Ped is by far the most benign of all GI prokinetics. There are NO overt neurological side effects. It's just the old-fashioned liquid pink bubble-gum flavored erythromycin. A tiny dose irritates the stomach and small bowl into emptying appropriately in a way that mimics a healthy GI tract. At 23, my son still takes an 1/8 of a TSP twice daily. It might be worth considering. He also takes probiotics to try to counteract the effect on his bowel.

LAC, I know you've been using mild ketosis to address your BG and cognitive issues? With your new diabetes DX and GI issues, are you still? How has your cognition been affected with all of this? Once again, I'm so sorry you're dealing with this, Honey. I'm sending healing energy your way. Please keep us posted on your progress.

[LA18]

Gilgamesh, interesting article. Thanks. I really do think I could benefit from the anti-inflammatory effects of LDN. Wish I could use potentially promising treatments like this without having to worry so much about side effects.

Juliegee, yes, I’m still on the ketogenic diet. HRT has helped my cognition substantially, but I’m still in the no/low ketones, no short-term memory category. Things are difficult right now because I’ve got to watch both my glucose and my ketone level. The rice is okay, but I miss my targets every now and then, and I’ve been taking too much MCT oil. When my ketone level drops below about 1.3, I still experience a profound decrease in cognitive ability. MCT oil turns my brain right back on. I need about 40 grams of carb from rice daily, in divided doses, to get where I need to be in terms of my ketone level while avoiding metabolic acidosis. Wish I didn’t have that issue - definitely not diabetic ketoacidosis, as my ketone level rises fast only when my blood glucose is low. This is probably due to my insulin secretion deficit.

Thanks for mentioning the effects of prokinetics on blood glucose. I’m guessing I’d be a good candidate for the big drops, given my history of hypoglycemia. I’m feeling bad just hearing your story. That must have been so frightening. It’s also motivating to recognize that recovery is possible. I knew you had gastro issues, but I didn’t realize they were so severe.

The erythromycin is a good idea. It’s affected my ears before, but that was at a much higher dose than what I would need for enhanced motility. I will definitely ask the doctor about this.

As for the diabetes, I no longer have a phase 1 or 2 insulin response, but my basal insulin production is normal, so I only need insulin when I eat carbs that aren’t low GI. The thought is that I have either an unknown form of MODY or mitochondrial diabetes. I think it’s the latter in part because CoQ10 has a profound effect on my insulin needs, which are now like those of a type one diabetic in terms of the carb to insulin ratio. In general, the insulin is going well. If I didn’t have to eat the rice, I would use it more sparingly, but it’s getting me through this, and I use it only in small increments. It doesn’t affect my cognition, unless I eat too many carbs and go out of ketosis, or I use too little and my blood sugar gets high. That knocks me out of ketosis pretty fast.

What type of bone broth did you use to facilitate your recovery? I’m thinking grass fed beef might be good.

[Julie G]

LAC, glad to see you’ve been able to still glean the benefits of the ketones, but sorry that you need them. I was hoping that the insulin may have had a positive effect on your cognition.

I highly doubt that your GI will be a fan of the Ery-Ped. It’s considered old school, but has the safest neurological profile by far of all GI prokinetics. If you do go that route, use a minuscule amount and titrate up as needed. Even motility specialists tend to prescribe dosages too high that end up being counterproductive- causing major irritation. It’s been eye-opening to see how little my son can take and still get a good benefit. I only took it for a few weeks to get me through a very rough patch. I’m hoping you’ll have a similar experience.

As you and I both know from experience that the super highway between the gut and brain is real. So many of the GI meds involved in motility are VERY dangerous to neurological health. When my dysmotility was very severe, my GI had me use super high doses of daily Miralax. The FDA has since issued a safety warning for associated neuropsychiatric events including dementia and Alzheimer’s:
https://www.gutsense.org/gutsense/the-r ... eimer.html

Susan recently wrote an excellent Wiki addition on our site about the vagus nerve that might be really helpful to you: https://wiki.apoe4.info/wiki/Vagus_Nerv ... al_Disease. With a motility disorder, your gut permeability is likely to be impaired. ANY bone broth will help with that. I know you need to avoid fiber, but a nutrient dense diet has been a key element to my recovery. I wonder if pulverizing veggies to a baby food consistency (like with a NutriBullet) would make them more palatable for you?

[LA18]

Julie, yes, duh on my part, it would make sense that the insulin would improve my cognition. I think my perspective is skewed these days – definitely operating on the good = no negative effect principle.

I took Miralax, per the recommendation of my gastric surgeon, until I saw your original post on its toxicity. Scary.

I’ve got a few more questions about your gut-healing protocol. If you don’t mind, I’ll PM you tonight about this. I really appreciate your input! Liz