REDUCING VLCFA COULD REDUCE SPASMS AND OTHER SYMPTOMS OF AMN.
I have been researching the literature on AMN and XALD for some time, and have decided to write this blog, as I have read all of your comments and blogs, and I am deeply concerned about what you are all going through, and I hope that some of my ideas might help to alleviate your symptoms.
Apart from stem cell therapy, the medical profession does not seem to have progressed very far in curing these diseases, and Lorenzo's oil even today appears to be the main means of controlling the diseases. (Please refer to my Sept 12th comment in RELAY's blog "AMN Mystery disease" for my own interpretation of the reasons why Lorenzo's oil is so successful at reducing the rate of VLCFA accumulation).
As you may know, the disease is caused by a mutation in the ABCD1 gene located on the X chromosome. This gene makes a protein that transports harmful very long chain fatty acids (VLCFA) into microscopic organelles called peroxisomes, which then destroy these VLCFA. Without this gene, those with AMN and XALD cannot remove the VLCFA from their bodies, and so the VLCFA gradually accumulate in their blood and tissues, resulting in gradually progressing symptoms.
Luckily there is a similar gene called ABCD2, which is not located on the X chromosome. Therefore every male child has one ABCD1 gene and a pair of ABCD2 genes for every cell in his body, and every female child has two ABCD1 genes and a pair of ABCD2 genes in each of her cells; this is responsible for the genetic implications of the disease described elsewhere.
A male AMN patient will therefore lack any functional ABCD1 genes, while his mother will have only one of her ABCD1 genes functioning, often resulting in her also experiencing AMN symptoms later in life.
The ABCD2 gene does the same job as the ABCD1 gene, although possibly not as efficiently. Therefore in theory, ABCD2 could be recruited as an alternative gene to reduce and abolish VLCFA accumulation in the AMN patient's body.The trouble is, the doctors have found it difficult if not impossible to reliably activate this second gene. Despite the use of statins, phytosterols to reduce cholesterol assimilation, and zero cholesterol ingestion therapies, the ABCD2 gene cannot be coerced into becoming activated.
I have thoroughly investigated this area, and I have found that the ABCD2 gene is only switched on when the nuclear receptor molecule called "peroxisome proliferator activated receptor A" (PPARa) is active. What happens is that the PPARa molecule must first be "flagged" by a molecular ligand. This flagged molecule now combines with another called the "Retinoid X receptor" (RXR), to form a complex (i.e: a molecular sandwich).
This activated complex now migrates into the nucleus and activates the ABCD2 gene, which can only then begin to produce ABCD2 transporters, which will in turn carry the VLCFA into the peroxisomes. Without this series of events, the ABCD2 gene will refuse to work, and remains switched off.
Therefore in order to get the ball rolling, I had to find the right flag. As I mentioned, the doctors tried statins, and reduced cholesterol to switch on another molecule called SREBP2, which is instrumental in cholesterol metabolism and showed promise in activating PPARa. But nothing really worked.
I found that although PPARa is sensitive to fatty acids, it is not sensitive enough. But it is highly sensitive to a molecule called Phytanic acid, which is present in vegetables as phytol, which is a part of the chlorophyll molecule itself. The bond between phytol and its parent chlorophyll molecule is very strong, and normal boiling does not release phytol from the vegetables. Also, our digestive systems cannot break down chlorophyll, so most of the phytanic acid passes through our systems as waste, and the little that we do absorb passes into the peroxisomes and is broken down.
I did some experimenting, and I found that spinach will release phytol if it is strongly boiled; and this phytol will ligand to PPARa and activate the ABCD2 gene.
Unfortunately I found out the hard way, by spilling highly concentrated phytol on my hand, which promptly developed dermatitis due to the simultaneous activation of ABCD2 as well as ABCD1, resulting in rapid depletion of VLCFA from the epidermal tissues, and destruction of the permeability barrier. (Fortunately I was able to devise a means of replacing the lost molecules and reversing the process, although this took months of trial and error).
If you want to try out these ideas, take a spoonful of mustard oil a day to reduce your fatty acid elongation process. Then back this up with a serving of strongly boiled spinach per day, using the boiled vegetable water as a broth. This should contain enough phytol released as available phytanic acid, and it will do no harm as it is not highly concentrated.
Once the phytanic acid has been absorbed by your digetive system, most will pass to the liver cells' peroxisomes for disposal, but there may be enough left over to ligand to PPARa molecules in some of your liver cells, pass to the nucleus, and activate some of your ABCD2 genes. This will allow your body to gradually reduce the accumulated VLCFA by creating ABCD2 transporters, which will carry VLCFA into the peroxisomes so they can be disposed of.
Alternatively you might prefer to try one "green smoothie" a day (This is uncooked vegetables and fruit mixed with ice cream and blended strongly). Many people enjoy green smoothies anyway, and they cannot harm you. I think that the mechanical stimulation from mixing in a high powered blender can break off the phytol tails from chlorophyll molecules in the vegetables, releasing valuable phytanic acid that can be used to activate ABCD2 genes.
I can make no guarantees of success, and you may have to keep up this "diet" for some months before you see any improvements. However, my friend who has AMN has been taking mustard oil and green smoothies for over a year now. He gets his blood tested regularly and I have tracked his fatty acids on a spreadsheet. It is quite amazing how quickly his VLCFA have declined, and they show no signs of levelling off, just a continuous decline. If this is matched by a decline of VLCFA from his tissues, it could be the turning point for his disease progression. Lets hope so.
If anyone out there feels that they want to try out these ideas, or if you want more information, copies of relevant papers etc, please contact me through ALDLIFE.
Also, if you do try this and your symptoms do start to improve, please let me know, so I can make up a progress report, and maybe we can gather some evidence that will convince the doctors to try new ideas such as these, once they have been proven to work. That way everyone will eventually benefit.
All the best,