I am glad you have brought up the subject of dopamin because many of the genetic mutations I am talking about influence the production of neurotransmitters. Below is the information I have, which came from my genetic analysis produced by my GeneticGenie report. It's a lot to read but worth it if you feel that you have a neurotransmitter imbalance.
dt
"Although we cannot change our genetic code, we can change how our genes are expressed. Research has revealed
that our gene expression is not determined solely by hereditary factors, but it is also influenced by our diet, nutritional
status, toxic load and environmental influences or stressors. This phenomenon has been termed "epigenetics".
Researchers in the growing field of epigenetics have demonstrated that certain genes can be over- or under-expressed
with certain disease processes. Researchers in this field hope that by understanding of how these genes are regulated
and what is influencing them, we may be able to change their expression. Using epigenetic concepts along with a
good understanding of the methylation cycle, researchers have begun to make recommendations to optimize genetic
expression and help to restore health."
"MTHFR A1298C is involved in converting 5-methylfolate (5MTHF) to tetrahydrofolate (THF). Unlike MTHFR C677T,
the A1298C mutation does not lead to elevated homocysteine levels. This reaction helps generate BH4. BH4 is
important for the detoxification of ammonia. The gene is compromised about 70% in MTHFR A1298C (+/+)
individuals, and about 30% in people with a heterozygous (+/-) mutation.
BH4 acts as a rate limiting factor for the production of neurotransmitters and catecholamines including serotonin,
melatonin, dopamine, norepinephrine, and epinephrine. A MTHFR A1298C + status may cause a decrease in any of
these neurotransmitters or catecholamines. BH4 is also a cofactor in the production of nitric oxide. A dysfunctional
BH4 enzyme may lead to mental/emotional and/or physical symptoms. Mercury, lead, and aluminum may act as a
drain on BH4."
"CBS (cystathionine beta synthase) catalyzes the first step of the transsulfuration pathway, from homocysteine to
cystathionine. CBS defects are actually an upregulation of the CBS enzyme. This means the enzyme works too fast.
In these patients, it's common to see low levels of cystathionine and homocysteine since there is a rapid conversion
to taurine. This leads to high levels of taurine and ammonia. The CBS upregulation has been clinically observed to
result in sulfur intolerance in some patients. It has also been observed that BH4 can also become depleted with a
CBS upregulation. BH4 helps regulate neurotransmitters and mood. Other mutations, such as MTHFR A1298C,
Chronic bacterial infections, and aluminum can also lead to low BH4 levels. Lack of BH4 can lead to mast cell
degranulation and possibly mast cell activation disorder (MCAD).
Note: While some physicians think the CBS mutation is one of the most important mutations to address, there is very
little medical research to support these claims and some doctors in the field disagree. In normal populations, studies
have shown CBS upregulations to be protective against high homocysteine. However, CBS upregulations have shown
to be harmful in Down Syndrome. Medical research has not determined if CBS upregulations are harmful in those with
syndromes or disorders leading to impaired methylation.
"
"MAO-A (Monoamine oxidase A) is a critical enzyme involved in breaking down important neurotransmitters such as
serotonin, norepinephrine, and dopamine. Males only have one allele since the gene is inherited through from their
mother since it is located on the X chromosome. Only females can be heterozygous (+/-) for this mutation. When a
(+/+) MAO-A mutation is combined with a (+/+) or (+/-) COMT V158M mutation, imbalances in neurotransmitters may
be more severe. These imbalances can potentially lead to neuropsychiatric conditions and symptoms such as
Obsessive Compulsive Disorder (OCD), mood swings, and aggressive and/or violent behavior.
Note: Genetic Genie reports the wild type as the defective variant as doctors have clinically observed that patients
with methylation problems (especially those of Autism) often have trouble breaking down neurotransmitters. The high
activity version of MAO-A (which is represented as -/-) can contribute to major depressive disorder. The significance
of this SNP should be interpreted with caution."
"COMT (catechol-O-methyltransferase) helps break down certain neurotransmitters and catecholamines. These include
dopamine, epinephrine, and norepinephrine. Catechol-O-methyltransferase is important to the areas of the pre-frontal
cortex. This area of the brain is involved with personality, inhibition of behaviors, short-term memory, planning,
abstract thinking, and emotion. COMT is also involved with metabolizing estrogens.
COMT (-/-) individuals can usually break down these neurotransmitters efficiently, but COMT (+/+) individuals may
have trouble breaking these chemicals down from impaired function of the enzyme. With a COMT + status, it has
been clinically observed by physicians that people may have trouble with methyl donors. This can lead to irritability,
hyperactivity, or abnormal behavior. They may also be more sensitive to pain."
"VDR (Vitamin D Receptor) encodes the nuclear hormone receptor for vitamin D3. Low or low normal vitamin D values
are often seen in those with chronic illness and even the general population. Low vitamin D is related to a lot of
neurological and immunological conditions. Vitamin D stimulates enzymes that create dopamine.
VDR Tak and VDR Bsm are usually inverse from eachother. So if there is a (+/+) VDR Tak, there would be a (-/-) VDR
Bsm. However, this is not always the case.
It has been clinically observed that the body may have trouble tolerating methyl donors with a COMT V158M + and a
VDR Taq + status. VDR Taq (-/-) individuals may already have higher levels of dopamine, and combinations of
variations COMT and VDR Taq can lead to a wide range of dopamine levels. Those that are VDR Taq (+/+) and
COMT (-/-) may have lowest dopamine levels.
Note: Some have pointed out that VDR Taq is reported backwards since majority of medical journals report a different
risk allele or use different notation. These arguments are well-founded, but Genetic Genie reports this way so results
are compatible with existing methylation nutrigenomics literature. Many claims about VDR and methylation are clinical
observations. There are no medical studies to support some of the observations"
"BHMT (betaine homocysteine methyltransferase) acts as a shortcut through the methylation cycle helping convert
homocysteine to methionine. The activity of the enzyme can be negatively influenced by stress. The Information on
this enzyme related to methylation is mostly based on Dr. Amy Yasko's clinical experience and research.
According to Dr. Yasko, a homozygous mutation of BHMT 01, BHMT 02, BHMT 04, can produce results similar to
one with a CBS upregulation even if you don't have a CBS upregulation. In her book, Autism: Pathways to Recovery,
She also states that a BHMT 08 mutation may "increase MHPG levels relative to dopamine breakdown (HVA)". This
can result in attention type symptoms. It is common to see elevated glycine in someone with a homozygous BHMT
08 mutation."
Dointime, this is really good information, thank you so much. I have said this before but just in case.
I heard a doctor talk on the TV, briefly, he mentioned that interferon could reduce our dopamin (feel good) chemical. L'Tyrosine can increase it. I tried it, it is helping me quite a bit. I feel better so I am doing more so I feel better and so on and so on.
Of course tried a lot of things. Tried Gauf's supplements from HepResearcher, could not keep up with the list
I pray that everyone will find help
D
or i will die in this search. 50 50
that's what I did the last year.
walking through the town, getting scripts for various drugs like prednisone and minocyclin, buying supplements like curcumin and vitamins... there will be the day when i have a script with the right drug in my hand and take the drug and feel like myself again. And the first thing i will do then is going here and tell you all!! :-)
Rick,
I have read through this thread and I think that you are exceptionally clear and confident at describing what has gone wrong with you:
"Way it was explained to me was that when you do the drugs they may or may not interfere with normal brain/body pathways ------- Sometimes more than one pathway is messed up and doesn't return to normal. Or chemicals in brain get released that weren't before and that disrupts the normal body functions "
-
I don't have your answer but this kind of before&after effect suggests to me that genetics is an area that you might look into. Chronic viral infection is a major reason why a gene which was turned off can get turned on and start to express something that changes the way your body works. I underwent a dramatic change in my body around the time that I think I got hepC, (from a gamma globulin shot). I got food intolerances for example, and my thyroid function slowed down. From gene testing I know that I am susceptible to coeliac disease but I didn't have it before - now I do. I didn't have any health problems before, just like you. Now I am struggling with fatigue, perhaps malabsorption, perhaps thyroid, perhaps coeliac, etc. Point is that when those genes get switched on they cause a transformation of the type you describe, and they don't necessarily get switched off again ever. tx is among the insults to the body that could cause previously dormant genes to spark up and set off a cascade of reactions.
-
you can get a relatively inexpensive saliva test from:
www.23andme.com
Their report can tell you what you are predisposed to have because of your genetics. Unfortunately it can't tell you which genes are expressing and which are not but you get a lot of information and clues that could be worth following up. And just because it is genetic does not mean you can't do anything about it. Lots of things can be compensated for but you need to understand them first. Your genes are underlying all your bodily processes. It can be very difficult to track down a faulty brain/body pathway. Genes make enzymes and enzymes are the switches that you may be looking for.
-
Best wishes,
dointime
Still here, still suffering 14 years later. Some times are better than others, some times are worse. There's no way to tell which are going to be which.
I understand that the Mayo Clinic acknowledges PIS. I've sent my records, let's see what happens.
I am so fortunate to have a home. My boyfriend is pretty tired of me because I'm so tired. Luckily he hasn't quit on me. I'm turning 62 this month. I did treatment at 47.
This was not the way I planned to live my life.
Ah I'm 26
Tx 2014 march, 12 wks ifn, sov, rbv
Same situation here, I am bedridden, tied to the bed, trying to make it through the day. Everything seems so senseless, I was a happy guy that everyone looked at when I entered a room...I loved to play music, to program, to cook....
That is all gone now.
I live a lonely life without friends without energy without words without love without future without hope ....
I really have no clue as to what is wrong with me
I know I was one way before TX and another after and getting worse each year
Because all of this effects everyone differently the medical community since they can't test it and say yes or no ----- for the most part ignores it
There are tons of theories as to what is damaged
Vitamins / Drugs / Food / Therapies ---- all band aids, the damage is done and irreversible is what I have come to believe
I keep trying and researching (trying to break it down into what I understand)
Damage in the cells / damage in brain stem / damage in the brain ---- we were wired a certain way to work properly and the medicines screwed it up
and it doesn't appear anyone can unscrew it yet
Maybe years from now they will figure it out, hopefully the new treatments are not doing the same as the old ones
Its like the Hep C virus went unnoticed in our bodies till we took the TX and pointed it out ------- Now our bodies are in full killer mode with no success--- Like having the flu and having the coughing / sneezing go away but still feeling like you have the flu because when you did your body was trying to kill it
Being the way I am, I will continue every day best I can till it becomes too much to take
All we can do is try, understand, and maybe help someone else to understand
That link you provided....I posted something about that trial years ago when it happened. These men's bodies swelled to about double their size, complete organ failures.
It was a chilling account, and one of the really chilling thing was that they did the trial to some extent in one location and at one time.
These men were dosed one after the other, and then started soon thereafter having horrendous reactions. Can you imagine watching it happen to one of the trial participants, and then waiting for it to happen to you?
I think that in retrospect they decided that it would have been much safer/smarter to dose the poor souls at intervals.
Somewhere on the internet there may yet be an account, but I can no longer provide you the account I originally linked.
http://www.newscientist.com/article/dn9734#.U8vC2UBz3XQ
============
Terrible story. I was just starting to look into trials at that time.
~W
Rick, I took a glance at this thread and my, I have to say you have come a long way from March - from doing meth to doing vitamins!
I treated with INF/riba as well but only lasted 12 weeks. I had a truck load of side-effects, however, and some of those are still around. My most severe reactions were dermatological, but I had the chronic fatigue and a destroyed immune system also. Three months after I quit tx I got a campylobacter GI infection (it hits the immunosuppressed - old people and infants) and my VL hit 7 million and was rising.
And of course I could barely walk around my house.
I did research as well and I found out that it was the riba that tears up your DNA and your mitochondria. HCV tears up your mitochondria on its own, but riba really tears it up. That's what chronic fatigue is all about - mitochondria, because that's where we make and store energy, and that is where we are impaired.
The list of stuff you are trying above is all great stuff. That's because they are classified mitochondrial nutrients. They are more properly termed metabolites, because they are part of your normal metabolism, or used to be anyway, before you damaged your mitochondria.
When One-A-Day vitamins makes an Energy claim for B vitamins and other mitochondrial nutrients, the FDA allows them to do that because it is the irrefutable truth that those nutrients have a positive effect on energy production. Five Hour energy uses mitochondrial nutrients plus a small shot of caffeine to boost energy. So the evidence is all around us, if you look.
For people who have been debilitated by these mitochondrial drugs for our mitochondrial disease, mitochondria nutrients make all the sense.
I would suggest that you keep educating yourself and buy into your new program. I have found that what helps is to take normal daily doses of the stuff, but split into three servings on a strict three servings per day serving schedule to maximize the tissue retention time.
And give it some time. Keep a journal for reference. Take BCAAs for brain fog, take N acetyl cysteine for glutathione production, which is one of the main deals for mitochondria, also phosphatidylcholine for your mitochondrial membranes. Plus all the mitochondrial nutrients. And have faith and be positive.
I know of a clinical trial involving these nutrient metabolites coming up in a couple months that is enrolling Veterans, through a new program called Operation Liver Health. Its out of Phoenix, but PM me if you want some details on it.
You might check out my Metabolomic Study post on the other Hep C site for more detailed info on nutritional supplementation.
Best of luck, man and thanks for your service, the VA system is messed up but some good things may come out of all this, at least you gotta hope,
Mike
Yes Rick, very well explained.
As my symptoms added up I learned that interferon was a cytokine and then someone brought up this horror story from Britain the same year!
TGN1412 - http://en.wikipedia.org/wiki/TGN1412 & http://www.flutrackers.com/forum/showthread.php?t=9332.
take care all and best of luck, f
there are no specialists,it took five years to get my diagnosis. I was diagnosed with post viral fatigue syndrome first and the similarities to M.E. are many but I really believed the treatment caused my current health problems and fought for a proper diagnosis.We all seem to be in the same boat here,our lives trapped in a horrible foggy painful tiring limbo.
succinctly put! thanks RickVaug-I have had a few conversations with my consultant regarding microglia activity where I've mentioned it but he never elaborates,it appears to be down to us patients to collate the information nowadays,when you have limited energy this can take years!.
You are trying to treat neurological damage from the combo TX
Way it was explained to me was that when you do the drugs they may or may not interfere with normal brain/body pathways ------- Sometimes more than one pathway is messed up and doesn't return to normal. Or chemicals in brain get released that weren't before and that disrupts the normal body functions
The mechanism of this injury to the brain appears to involve the brain's special immune cell called the microglia. Normally, these cells remain dormant in the brain. Once activated, microglia can move about the brain secreting very toxic compounds.
Interferon is a cytokine and there are so many things it does down on the cellular level they aren't sure what damage or changes it can cause to occur
When you sleep you wake up refreshed because body rebuilds itself ------ if the pathways that were used for that become disrupted ----- You now wake up feeling like you haven't slept, every time you do a normal activity ---- it wears you out
It's a horrible way to live and hopefully it is just temporary for you ---- There is no treatment because they haven't a clue as to which pathways get changed / messed up so all they tell you to do is accept it and live the best you can
Hope all this passes for you
This sounds very familiar... I've started taking shots of B12 twice a week. Also doing a mineral and Vit C drip once a week and acupuncture 3times a week. The B12 definitely helps. Maybe the rest of it does too. Still don't know what I'm treating.
Hi otterwatcher,
I did 11 months of a combo experimental treatment in 2007-08 (ribo, int. and bocefivir) It was successful and I returned to a relatively robust condition (for a 58 year old man) after a year or so. A year ago I started getting sick on and off, knocked out with ME/CFS like symptoms. I thought I had Lyme's disease. I still might. 5 weeks ago it returned. I'm unable to walk 20 minutes without fatigue and headache. I live in Thailand and will be flying to US to get some answers. (I've been to 8 different specials here and all my tests are normal.) I'm targeting doctors who specialize in ME/CFS and Lymes. You mentioned Post Interferon Syndrome. It's the first I've heard of it. Are there specialists dealing with this issue?
I got thru each day saying "one more day" ----- "One more week" and just accepted that I felt miserable because of the TX ----- NEVER expecting that it wouldn't ever go away
I honestly slept for 3 days after shot and slept 50% of next 3 days ----- kinda felt okay the last day and then do it all over again
Essence / Mojo / Love of Life / The thing that made you enjoy life is what I miss most too
yes I think they've helped! I felt better the 2nd day! I'll only take them for 2 months see how I go-am only taking 100mg in the morning but I certainly feel more positive.This may also be because it's Spring and the sun has been out!
I'm not on any other anti deps-I hate them too,nasty things
I was prescribed citalopram post tx but didn't get on with them.
I just toughed out treatment too but looking back I would say by week 11 I was depressed-how could you not be? I was expecting the physical sides,I'd seen folk go through chemo but NOBODY told me my brain would be turned to mush and I'd lose my essence.
Have you tried the 5 HTP ?
It sounds like it was studied for being on the IFN to minimize associated depression
Whats funny is I had no depression while on TX. Which is why I am probably why I am in the condition I am in. I had a positive outlook and toughed it out when I should have called it quit, and the long term of the TX is what thru my system out of whack
I think that is why the anti-depressants made me want to kill myself
I hope the new treatment makes you SVR AND clears up some of your problems
Cooking ----- no desire to put whats required to make a wonderful meal --- eating have to do it and make it as healthy as possible
The cytokine storm is stuff released into brain ---- My CFS specialist recommended I get Omega 3 from Chia ----- If it doesn't help I am gonna make a pet with the leftovers
i am so tired..4 years now…
cytokine storm is interesting..came across that term last year.
really depressed today. there are so many things i want to do. and yes typing hurts ... pain in arms and legs..tired..need to cook and eat vicious circle..
how are you guys doing?
i see some docs next week… may start sovaldi olysio.. ?
The depression always seems to be for folks taking the TX not for us folks left in the aftermath of destruction
I haven't ---- I over did it yesterday (did some yard work) and am going back to bed after being up 45 minutes so far
Everyone take care of themselves
... a bit sick right now... over did it with the 70F wind storm cycling day then we had 50F rain & wind storms which brought me migraine headaches! and now we are back in the 30F!
I was probably born to be a cyclist or that is what I have been told. Even during treatment I would do about 10 - 20 miles / day. I did 72 weeks of treatment. I did a ton of hiking and walking during the winter as well. I feel the hills of PA are even worse that the hills of San Francisco!
I have such a passion for cycling. SF brought even for of it to me. I discovered single gear cycling there. Free wheel and fixed gear. I bet otter that you would be able to pick up my silver fixed gear! It is really light. But then it only has a front break - don't really need it if you're strong enough to control the rear wheels with your leg muscles! No relaxing on a fixie! But what a speed demon.
Looks like the electric toothbrush I have, a Braun - isn't a sonic - don't think that is the issue... seems my teeth are rotting from the inside out. We do have fluoride in our water, toothpaste. When I tell the dentist I have an electric toothbrush. They still say I am brushing too hard. I tell them the thing stops when I brush too hard. They can't say anything then. I have no bleeding etc. I floss all the time but not aggressively, Whatever... Will ask if a sonic will do any difference.
That 5HTP sounds interesting otter. I don't know what makes me able put so much positive power forward but it is what I do. It takes sooooo much energy to put on a happy face every day. I don't let on my true self! It would be disastrous! I do take an anti-anxiety pill morn and nite which I know helps a lot.
Did you start that other thread Rick?
OK, going to try to sleep off this headache.
Best to all,f
I knew as soon as I didn't improve post treatment that the drugs had damaged me.It took 5 years to finally get a diagnosis of Post Interferon syndrome.I know exactly how you feel.However you do still have hep c and as the liver is the body's engine this may well be contributory to you feeling fatigued.Energy borrowed has to be paid back so you probably found that you had a few days completely whacked out post your experiments,it may well have been delayed so you didn't associate the two.If you have liver damage and hcv you really shouldn't make it work any harder than it already is so I'd leave out the chemicals-tempting as it may be to have a 'normal' day! I found cutting gluten/chemicals has helped and pacing myself very strictly can leave some spare energy now and then-it's life Jim but not as we knew it!