8 replies to this topic

[NeuroNootropic]

So I've been taking methylfolate since 2015 and its effects have been largely double-edged. It's affected some parts of my life in a very positive manner but worsened others.

 

Dosing methylfolate is a complex thing. Too much and I get very severe brainfog, depressed mood, worsened anhedonia, irritability and worsened focus. Too little and I don't feel anything. Taking it everyday results in too much. It's not even a matter of the dosage, it builds up in my system and it's like a snowball effect. The dosage only affects how fast too much methylfolate builds up.

 

To make things even more complicated, I need take vitamin B12 regularly to make sure that methylfolate trapping doesn't occur. I take B12 in the form of methylcobalamin and this too builds up in my system. Once a week dosing improves my mood, focus, energy, and motivation, but taking it everyday results in fatigue, irritability, and just undoes all the benefits of methylfolate.

 

Anyway, here's what methylfolate does for me:

 

Benefits

• Greatly improved focus - Sustained attention is a lot easier. I no longer have 1000 thoughts in my head at once. Instead, I can direct my attention to a single thing
• Slightly improved energy - It's a bit easier to get up from bed, but I still sleep for 10-12 hours

Side effects

• No spontaneous actions / Robotic, zombie-like feeling - Everything I do is calculated or based on an objective. Nothing is spontaneous. Basically, I have absolutely no desires whatsoever. Nothing pops into my head. In other words, it makes anticipatory anhedonia very severe, probably 10/10 compared to my baseline 8/10.
• Poor memory and learning ability - My short-term memory has always been good, but since I started taking methylfolate I now have a very poor short-term memory. Even more so is my long-term memory. Methylfolate directly worsens my memory. Despite having good focus, learning new things and concepts is very difficult
• Blunted effect from antidepressants, stimulants, and supplements - It's like methylfolate blocks all the positive effects of substances that once used to relieve me of my anhedonia. Wellbutrin and Rhodiola Rosea no longer have that distinct honeymoon period where laughter comes naturally and feels good. Stimulants no longer give me motivation and what's more is stimulants now worsen my focus and learning ability whereas before they improved both areas
• Probably decreasing my already low appetite - I literally only eat 1 meal a day now. I can't stand eating. Nothing tastes good, everything is blah.
• Brainfog - My ability to conceptualize abstract ideas in my head has disappeared. I can barely think
• Reduced verbal fluency - In addition to the brainfog, my overall vocabulary has decreased. As in, I can only use very basic words to communicate now.
• Stuttering when talking - When engaging in conversations I'll often repeat a word 2 or 3 times
• Reduced motivation
• Slower processing speed - It takes me a while to understand even basic instructions now
• Zero creativity

 

There are more side effects but I just can't remember them now.

 

Nowadays, I literally only take methylfolate for the focus and energy it gives me. Every time I try to stop it, my old, 1000 thoughts at a time, self comes back and it's very frustrating because it pretty much disables me. When you have 1000 thoughts at once, sustained attention goes out the window = zero productivity.

 

I don't know, should I just stop the methylfolate and replace it with daily dexedrine at 5 mg? Dexedrine is such a hit and miss that I rarely take it nowadays. Sometimes it improves my focus and motivation, other times it just makes me depressed and even worsens my focus.

[iseethelight]

Stop taking it. The negatives way outweigh the positives. I had to drop it too due to it causing my anhedonia to worsen.

[RYAN474]

I get similar upside and downside from methylfolate, although I have not tested it systematically. I take it as part of a B-vitamin complex once per day in the evening. Also, when my mood isn't the best or anxiety is a bit high and I want the ability to smile more easily and interact better socially, I will take 50 to 100 mcg of methylfolate during the day prior to the social interaction. It has a distinctive effect of allowing me to smile more readily (mood improvement). However, I believe it then contributes to lack of motivation and brain fog later in the day. When I was dosing folic acid, it had similar effects, but not as pronounced as methylfolate. 

 

I take generic adderall immediate release (prescribed for ADD-PI), which helps with sustained attention and everything else. Dexedrine never worked for me. So if you have the ability to access adderall, I would encourage trying that. Just know that different generic manufacturers work very differently for different people. For me, taking adderall at higher doses (i.e. 40-50mg/day) can sometimes (but not usually) make me a bit more robotic and affect my social interactions. Especially when i'm sleep deprived or have other factors like diet that are causing issues. So that's when I add a bit of methylfolate, for important meetings/ social interactions. I prefer theanine to methylfolate because theanine does not seem to cause the issues methylfolate does, but theanine also doesn't give me that 'ability to smile' that methylfolate or folic acid does. Theanine does help with focus quite a bit. 

 

[NeuroNootropic]

So I last took methylfolate on October 05 and I feel as though it's 80% out of my system. Today, I took instant release methylphenidate at 10 mg and had a small increase in motivation, mood, and focus as well as a small decrease in fatigue and brainfog.

 

Over the past few days I've noticed that my old self was coming back, both the positive and negative:

 

Positives

• My emotions have increased a bit.
• Music sounds a bit better. I never listened to music while on methylfolate
• Brainfog has decreased from a 10/10 to 7/10
• Motivation has increased a bit

Negatives

• Sleeping 12 solid hours again. Waking up is pretty much impossible because of how deep I sleep. On methylfolate, I could wake up after about 10 hours.
• Reading is very difficult now. My eyes will read the words but my brain will be thinking of something else. Methylphenidate seems to have helped with this though

I get similar upside and downside from methylfolate, although I have not tested it systematically. I take it as part of a B-vitamin complex once per day in the evening. Also, when my mood isn't the best or anxiety is a bit high and I want the ability to smile more easily and interact better socially, I will take 50 to 100 mcg of methylfolate during the day prior to the social interaction. It has a distinctive effect of allowing me to smile more readily (mood improvement). However, I believe it then contributes to lack of motivation and brain fog later in the day. When I was dosing folic acid, it had similar effects, but not as pronounced as methylfolate. 

 

I take generic adderall immediate release (prescribed for ADD-PI), which helps with sustained attention and everything else. Dexedrine never worked for me. So if you have the ability to access adderall, I would encourage trying that. Just know that different generic manufacturers work very differently for different people. For me, taking adderall at higher doses (i.e. 40-50mg/day) can sometimes (but not usually) make me a bit more robotic and affect my social interactions. Especially when i'm sleep deprived or have other factors like diet that are causing issues. So that's when I add a bit of methylfolate, for important meetings/ social interactions. I prefer theanine to methylfolate because theanine does not seem to cause the issues methylfolate does, but theanine also doesn't give me that 'ability to smile' that methylfolate or folic acid does. Theanine does help with focus quite a bit. 

 

I suspect that it's the decrease in noradrenaline release that causes the brainfog and decreased motivation. Methylfolate has been shown to decrease noradrenaline release by a huge factor:

 

Wehave previously shown that 5-methyltetrahydrofolate influences neuro-secretion. The present study more precisely characterises the processes involved and considers one probable site of action. Focusing on the tyrosine-noradrenalin axis in cerebellum we showed 5-methyltetrahydrofolate causes a significant reduction in the apparent K+ evoked secretion of noradrenalin to only 12.9% of control release. Evidence supports the idea that this could actually be due to increased synthesis leading to; depletion of reserves, possibly through leakage, exocytotic inhibition via activation of presynaptic receptors or end product inhibition by noradrenalin at the pteridine cofactor level of tyrosine hydroxylase: a) concomitant decreased measurement of perfusate and intracellular tyrosine with released noradrenalin following 5-methyltetrahydrofolate treatment supports the idea of increased transmitter turn over; b) kinetic studies indicate that at saturating concentrations of tyrosine and in the presence of an inhibitor of L-DOPA decarboxylase, 5-methyltetrahydrofolate partially duplicates the rate limiting behaviour of a synthetic pteridine cofactor--DL,2-amino-4-hydroxy-6,7,dimethyltetrahydropteridine. We debate whether, in vivo, CSF 5-methyltetrahydrofolate might interact at the tetrahydrobiopterin cofactor level of tyrosine hydroxylase and other aromatic amino-acid hydroxylases.

→ source (external link)

 

Noradrenaline is very important for dopaminergic neurotransmission and without it, dopamine is all but useless. That said, it seems that the combination of salts in adderall has a synergistic effect on increasing dopamine release. Levoamphetamine, which increases noradrenaline release, is purported to be responsible for this.

 

Considering the noted in vitro observations of DAT, we propose L-amphetamine in Adderall® may be altering DAT function or availability to regulate the efficiency by which DA is allowed to pass through

 

RESULTS:
Local applications of Adderall resulted in significantly greater DA release signal amplitudes with prolonged time course of dopamine release and re-uptake as compared to D-amphetamine and D,L-amphetamine.

CONCLUSIONS:
These data support the hypothesis that the combination of amphetamine enantiomers and salts in Adderall has effects on DA release, which result in increased and prolonged DA release, compared to D- and D,L-amphetamine.

→ source (external link)

[JellyRev]

methylfolate is going to do more than the methylation cycle. Stop taking it. There are better options. Getting trapped thinking about the methylation cycle is overrated. most deficient brains will improve on mod/adrafinil. There is always Mao and Comt to think about. There is always the more rare pathways like acetylcholine. You problem does not sound like a methylation problem. 

[j87]

William Walsh says to avoid folate if you're undermethylated.

Edited by j87, 20 October 2017 - 08:06 PM.

[GreenmachineX]

Interesting thread. Any more headway gained here? I have the same problem with folate and wonder if I just need more b12 to make it usable...

[RYAN474]

An update from what I posted on 15 Oct 2017 11:33am: 

 

I recently saw an MD who does hyperbaric oxygen and other therapies for various chronic conditions. She suggested that I was "overmethylated" and should stop taking methylfolate, methyl b-12, and any supplemental form of any methyl donor. I had progressively decreased methylfolate and methyl b12 over time prior to that anyway, because I noticed they gave me more brain fog. I had never cut them out completely for any extended period of time.  Each time I tried to cut out one or the other, my mood dropped. 

 

However, this time cutting them out completely proved helpful for cognition. I also cut out sulfur rich supplements like NAC, glutathione.  To my surprise, my cognition improved quite a bit. I then worked with a progressive dietitian who suggested I trial a low sulfur and low thiol diet. This helped my cognition even further, although it is an extremely restrictive diet to live on. I don't care as long as I have my brain back. I believe the theory is small intestinal fungal overgrowth contributes to an overabundance of sulfur producing bacteria, so rebalancing that should eventually allow me to reintroduce other foods. 

 

I also take adderall, deprenyl, galantamine, intranasal insulin, magtein, and many other prescription and nonprescription things to improve cognition. 

 

 

 

 

[GreenmachineX]

I also believe I have a yeast overgrowth and will be doing a mild Candida diet and supplement program here soon.