• Phoenix Rising needs funds to operate: please consider donating to support PR

Vitamin D may be vital for the efficacy of low-dose naltrexone (LDN)

Hip

Senior Member
Messages
14,644
Likes
28,735
I just came across the following comment by researcher Prof Angus G Dalgleish about how vitamin D3 (cholecalciferol) is vital for the clinical efficacy of low-dose naltrexone (LDN):
Subject: ME/CFS

Dear Sir/Madam

I am an active researcher in Low Dose Naltrexone (LDN), and have shown that it uses TLR 9 as a receptor in addition to the opiate ones. ( Patent applied for and publication submitted)

I have also shown it enhances a gene set at low doses that are turned off at higher doses which may also explain the extraordinary clinical responses reported to date. Patent and in press( IJC, Liu et al).

My colleague Jonathon Brostoff reports that over half his patients are cured within 3 weeks with LDN treatment. The other half do not improve but I suspect they are vitD3 low as this appears vital for LDN clinical activity in other conditions especially Multiple Sclerosis.

Source: NIH Request for Information on ME/CFS Research Efforts
I cannot find any other references for low levels of vitamin D3 making LDN less effective, but for anyone who is thinking of trying LDN, it may be an idea to supplement with say 5,000 to 10,000 IU of vitamin D3 daily for several weeks before starting LDN (and continuing to supplement while taking LDN), to ensure vitamin D levels are adequate.

Note that it takes several weeks of supplementing to slowly build-up blood levels of vitamin D; so you'd probably want to start taking vitamin D first for a few weeks, before starting on LDN.

And for those already benefiting from LDN: it is possible that the addition of vitamin D3 might further improvement the benefits.

Dr Chia finds that LDN only helps a small subset of ME/CFS patients, but for those it helps, it does so very significantly. Perhaps if LDN were to be taken in combination with vitamin D3, a higher percentage of ME/CFS patients might respond to it.



The Possible Synergistic Mechanism of Action of LDN and Vitamin D

A possible mechanism of action that might explain why vitamin D is synergistic with LDN is as follows. First, note that LDN has a number of effects that may underlie why it can be helpful for ME/CFS and other diseases:

Low-Dose Naltrexone Physiological Effects:
  • Blocks TLR-4 on microglia, inhibiting microglial activation.
  • Antagonizes TLR-9, as well as TLR-7 and TLR-8.
  • Increases levels of met-enkephalin (aka opioid growth factor) and its receptor.
  • Blocks the mu-opioid, delta-opioid and kappa-opioid receptors for a short while (thought to up-regulate endorphins).
  • Has an effect on the nociceptin system.
  • May reduce peroxynitrite and thereby increase astrocyte glutamate transport. Ref: 1
In the case of LDN's effects on TLR-4, a number of studies have shown that vitamin D down-regulates the expression of TLR-4, so vitamin D may act synergistically with LDN in reducing overall TLR-4 activation, thus inhibiting microglial activation. Refs: 1 2 3 4 5 6 7



Combining Vitamin D With other Immunomodulators Like Oxymatrine

Supplementing with vitamin D might be of benefit with other immunomodulators like oxymatrine. Oxymatrine has also been shown to down-regulate the expression of TLR-4, which in turn reduces microglial activation. Refs: 1 2 3 So adding a vitamin D supplement (or doing lots of sunbathing) to your oxymatrine protocol might further enhance the effects on TLR-4.

Interestingly enough, @gregh286 found that when he first tried oxymatrine (Equilibrant) it had no effect on his ME/CFS. But when he re-tried oxymatrine later, but this time taking 25,000 IU of vitamin D3 daily, it led to substantial improvements. Ref: 1
 
Last edited:

kangaSue

Senior Member
Messages
1,573
Likes
2,309
Location
Brisbane, Australia
Last edited:

kangaSue

Senior Member
Messages
1,573
Likes
2,309
Location
Brisbane, Australia
I think you can also take vitamin D3 transdermally, @kangaSue, by mixing the powder from a capsule into an oily substance like an ordinary skin cream, and applying to the skin.
Thanks Hip and if I could, I would but I can't fathom what's going on with my gut as I can't do anything transdermally anymore without causing severe abdominal pain if it's left on longer than about 1/2 an hour.

Anything containing an oil is worst and have had to stop using all skin lotions and potions but even aloe vera inner gel straight from the plant gives me serious grief.

Vitamin D3 injections are the only option as I have sudomotor dysfunction too, don't have a normal sweat response so sitting in the sun is out too.
 

flitza

Senior Member
Messages
136
Likes
186

flitza

Senior Member
Messages
136
Likes
186
I just came across the following comment by researcher Prof Angus G Dalgleish about how vitamin D3 (cholecalciferol) is vital for the clinical efficacy of low-dose naltrexone (LDN):


I cannot find any other references for low levels of vitamin D3 making LDN less effective, but for anyone who is thinking of trying LDN, it may be an idea to supplement with say 5,000 to 10,000 IU of vitamin D3 daily for several weeks before starting LDN (and continuing to supplement while taking LDN), to ensure vitamin D levels are adequate. Note that is take a few weeks of supplementing to slowly build-up blood levels of vitamin D.

And for those already benefiting from LDN: it is possible that the addition of vitamin D3 might further improvement the benefits.

Dr Chia finds that LDN doesn't seem to help many ME/CFS patients, but for those it helps, it does so very significantly. Perhaps if LDN were to be taken in combination with vitamin D3, a higher percentage of ME/CFS patients might respond to it.



The Possible Synergistic Mechanism of Action of LDN and Vitamin D

A possible mechanism of action that might explain why vitamin D is synergistic with LDN is as follows. First, note that LDN has a number of effects that may underlie why it can be helpful for ME/CFS and other diseases:

Low-Dose Naltrexone Physiological Effects:
  • Blocks TLR-4 on microglia, inhibiting microglial activation
  • Increases levels of met-enkephalin (aka opioid growth factor) and its receptor
  • Blocks the mu-opioid, delta-opioid and kappa-opioid receptors for a short while (thought to up-regulate endorphins)
  • Has an effect the nociceptin system
  • May reduce peroxynitrite and thereby increaseastrocyte glutamate transport. Ref: 1
In the case of LDN's effects on TLR-4, a number of studies have shown that vitamin D down-regulates the expression of TLR-4, so vitamin D may act synergistically with LDN in reducing overall TLR-4 activation, thus inhibiting microglial activation. Refs: 1 2 3 4 5 6 7



Combining Vitamin D With other Immunomodulators Like Oxymatrine

Supplementing with vitamin D might be of benefit with immunomodulators like oxymatrine. Oxymatrine has also been shown to down-regulate the expression of TLR-4, which in turn reduces microglial activation. Refs: 1 2 3 So adding a vitamin D supplement (or doing lots of sunbathing) to your oxymatrine protocol might further enhance the effects on TLR-4.

Interestingly enough, @gregh286 found that when he first tried oxymatrine (Equilibrant) it had no effect on his ME/CFS. But when he re-tried oxymatrine later, but this time taking 25,000 IU of vitamin D3 daily, it led to substantial improvements. Ref: 1
I wonder if people in sunny climates respond better....
 

kangaSue

Senior Member
Messages
1,573
Likes
2,309
Location
Brisbane, Australia
Why can't you tolerate oral Vit D3. What side effects do you experience?
I have a severe chronic GI dysmotility problem. Lipid soluble vitamins were the first to cause problems (nausea, churned up stomach, abdominal pain) but now that's pretty much my response to everything except for a very short list of safe foods.
 
Messages
1,294
Likes
4,126
@Hip Thanks greatly for the info! :)

I take 10,000 IU of Vitamin D3 daily. Perhaps that's part of why I respond so well to LDN. I take 9mg of LDN at bedtime.

When I had my Vitamin D3 levels at over 100 ng/mL (25-OH), I actually felt better. But my doctor told me that was too high and to bring it back down below 80 ng/mL. However, that doctor recently retired, so I think I'll try raising my Vitamin D3 levels up a bit again.

I also plan on experimenting with my LDN dose. Recently I reduced it from 9mg to 6mg, but after a couple weeks my sleep and anxiety worsened. So I'm back at 9mg. Next I'll raise it to 12mg and see how that goes.

Edit: I should note I've never been on an LDN dose below 4.5mg. I was started at 4.5mg (Open Medicine Institute) and it was raised from there. I'm always astonished by people that respond to very small doses of LDN, as I generally feel like I need more.

Edit: I'm now on 12mg LDN and 15,000 IU Vitamin D3. Tolerating it well. I'll give an update in a couple weeks on how it's going.
 
Last edited:

sb4

Senior Member
Messages
1,358
Likes
2,201
Location
United Kingdom
don't have a normal sweat response so sitting in the sun is out too.
I have had this problem for a while however found, to my suprise, rubbing butter on my skin allowed me to start sweating again (maybe it's due to the dry skin, dry mouth, gastroparesis with some type of POTS). Also, obvious things like not being in the sun after eating help also.
 

flitza

Senior Member
Messages
136
Likes
186
For anyone else like me who has a problem with tolerating oral Vitamin D tablets, you can get vitamin D3 cholecaciferol as intra-muscular injections ranging from 200,000 to 600,000 i.u.

I can't take a 1000 i.u. tablet but a 600,000 i.u. megadose injection caused no untowards symptoms at all.
https://www.mja.com.au/journal/2005...-megadose-cholecalciferol-treatment-vitamin-d
If you don't mind my asking, what problems do you experience when taking the tablets?
 

flitza

Senior Member
Messages
136
Likes
186
I have a severe chronic GI dysmotility problem. Lipid soluble vitamins were the first to cause problems (nausea, churned up stomach, abdominal pain) but now that's pretty much my response to everything except for a very short list of safe foods.
Well there we go with brain fog. I asked you that question already. Sorry.
 
Messages
1,294
Likes
4,126
I should update that I felt worse on higher doses of LDN and Vitamin D3.

So I'm back to my usual 10,000 IU Vitamin D3 and 9mg LDN daily.
 

PatJ

Forum Support Assistant
Messages
5,098
Likes
14,495
Location
Canada
I've read that the optimum dose for LDN is 4.5 mg before bed.
Many people have found that the most effective personal dose varies from ultra-low-dose (0.025mg) to 25mg (for MS patients). I aimed for 4.5mg but encountered anxiety past 4mg. My current effective dose is 2.5mg.

Here is some information about dosing which includes this statement:
"Although the optimal dosage of LDN for the average adult (presumed to weigh 150 pounds) is considered to be 4.5 mg, some patients do much better (i.e., have fewer side effects and a better response) on a lower dose. [To compute the suggested dose for children and pets, multiply their weight in pounds by a factor of .03.] Adult dosage can be affected by a number of factors, including liver functionality, age, and metabolic rate."
 

frederic83

Senior Member
Messages
296
Likes
278
Location
France
Can't go more than 1.5 mg with LDN, otherwise I have anxiety at one point. 0.5-1.5 is ok for me. It helps with mood, over 1.5 I have mild insomnia. Nothing to report for the fatigue.
 
Last edited: