Hip
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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 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:
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
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
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
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