- 29 Dec 2017 22:50
#14875296
I look at orthomolecular options, because medical doctors almost always overlook them. Depression can be caused by a depletion of key nutrients. For example, hypomagnesemia (magnesium depletion or deficiency) can cause all sorts of problems. Magnesium is important for 325 different enzymes in the human body. All kinase enzymes require magnesium as a prosthetic in order to make them biochemically active. There are 103 kinase enzymes in the human body, so that's almost 1/3 of the enzymes requiring magnesium.
One important reaction is pyridoxal kinase. You should get reasonable amounts of pyridoxine or pyridoxamine in your diet--i.e., vitamin B6. However, it is metabolically inactive in that form. It gets oxidized in the liver to pyridoxal. Then, it gets phosphorylated into pyridoxal-5'-phosphate (P5P)--the metabolically active form. The pyridoxal kinase enzyme, of course, requires magnesium. Additionally, Adenosine Triphosphate (ATP) also requires magnesium. So in that reaction, ATP gives up a phosphate group to pyridoxal and becomes Adenosine Diphosphate (ADP), the added phosphate group to pyridoxal binds to the 5-prime end of the carbon atom giving you pyridoxal-5'-phosphate. ATP is important because it's the energy regulator in the human body. If ATP isn't working properly, you'll be pretty lethargic/apathetic.
Why pyridoxal kinase, pyridoxal, ATP and magnesium are so important in depression is that three key neurotransmitters are dependent on P5P:
1. GABA: Gamma amino butyric acid (GABA) is the primary inhibitory neurotransmitter in the human central nervous system. Ironically, it is synthesized in vivo from glutamic acid (or glutamate) which is the primary excitatory neurotransmitter. So if you don't have enough P5P for the glutamic acid decarboxylase enzyme, you end up with a build up of glutamate and a dearth of GABA which makes people excitable and agitated. Doctors will ignore that and prescribe drugs like benzodiazepines to counteract anxiety. Longer term, they will prescribe drugs like gabapentin to block the effects of glutamate. I've talked to doctors who were knowlegable about the GABA/glutamate balance/imbalance, but none of them knew that glutamate was the substrate for GABA.
2. 5-HT: 5-hydroxy-tryptamine (or serotonin) is a key neurotransmitter for regulating the nervous system. People with a dearth of it tend to get depressed, anxious, etc. Many anti-depressants are serotonin selective reuptake inhibitors (SSRIs). The metabolic path for serotonin can get shut down because of a lack of L-tryptophan in the diet. It also gets disrupted in women in another case: PMS. When estrogen spikes, it can bind to tryptophan hydroxylase, which breaks L-tryptopan down in to 5-hydroxytryptophan (5-HTP, which you can get at most vitamin stores). 5-HTP gets decarboxylated into serotonin with, you guessed it, P5P/B6 as a co-factor. There is another case where that gets blocked too. Some people with bi-polar disorder cycle with high degrees of dopamine, which can bond to and deactivate tryptophan hydroxylase too, just like estrogen. However, the mania from too much dopamine is followed by irritability and depression; hence, so-called "bi-polar" disorder.
3. Dopamine: Dopamine is key to what makes you feel good. The pleasure from sex, the satisfaction after a good meal, the "aha" when you learn something new generally comes from dopamine. The "keep doing this" aspect of addiction is also generally dopamine related. It uses exactly the same enzyme as 5-HTP in decarboxylating 5-HTP into serotonin; however, it decarboxylates L-Dopa into dopamine. Just like that reaction, it requires P5P, phosphorylated vitamin B6, to be metabolically active.
So I like to look at magnesium, zinc, potassium and b-vitamins as a baseline before looking at drugs.
I've talked to you about my friend before. She had a migraine from Christmas Eve until Wednesday evening. Where 800mg of Ibuprofen multiple times a day did nothing; where her migraine drug (a barbiturate + acetaminophen + caffeine) didn't help much, I found that as little as 250mg of magnesium began to clear the head pounding symptoms almost immediately. It took me awhile to realize that magnesium might help, but once I did the relief was almost instant. So I've got her taking about 750mg of it a day, which is almost 2x the RDA. So I added zinc and potassium to that mix, just to get some basic metabolites going.
Effexor is a NET and SERT drug. It binds to neurotransmitter transporters.
NET is the norepinephrine transporter. It makes me wonder if that binding is what was effective.
I have what I call the "motherfucker" gene, because its initials are MTHFR, or methylfolate reducatase. If I start getting down, turning it around for me is as simple as taking vitamin b9 (methylfolate) and vitamin b12 (methylcobalamin).
Some people have a COMT (catechol-o-methyltransferase) gene that makes them agitated and depressed too. The supplement SAM-e helps with that.
How is her diet?
Also, Swanson Vitamins has combinations for B9/B12 for the MTHFR gene. It also has a nice one called GABAplex, which contains GABA, Tyrosine (a precursor to dopamine) and a bunch of the soothing aminos like Taurine and L-Theanine.
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