I would say that your friend should just go back to her GP though she might need to accept that all causes of fatigue are organic
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I have lots of thoughts on this, having fought my way through this issue repeatedly as my body changed through menopause.
I usually spend a fair bit of time on my posts, and am careful with what I say. I don’t have that time right now.
(Quick aside: “excessive amounts of B12” is only what can be measured in serum. B12 isn’t stored in serum, so this is slightly irrelevant if her body isn’t using it well. She might need co-factors–other pieces of that puzzle. This includes but is not limited to lithium (orotate), folate (bioavailable forms only), carnitine, potassium.)
Also note that what you don’t take is as important as what you do. If you are one of the large percentage of population for whom folic acid paradoxically blocks folate absorption, not taking FA is essential.
My guess–and this is ALL my guess; without being her, or being in her body, it’s anyone’s guess-- is that she is right: it’s hormonal.
The medical establishment is not good at supporting women in menopause. To put it mildly. (I deleted a rant here.) Tell her it’s not her imagination if she feels medicos are discounting her symptoms.
Here’s where I’d start, if I were her advisor: vitamin D, magnesium (anything but oxide), and pregnenalone, all OTC. I do not recommend exact doses unless I have a direct connection with a person. If she’s not taking these, I highly recommend she does.
If she’s not on bioidentical HRT, I recommend she find a provider who can support that. Specifically Estridiol/E2 & progesterone. If she doesn’t want to do that for some reason, I might have further suggestions.
Without knowing more, that’s as far as I’ll go.
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Thank you so very much. I’m sharing your post with her now 
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Thank you again!
My friend was very grateful for your thoughtful reply. She would like to know if there is a test or some way of knowing whether she is one of those people you describe:
“ If you are one of the large percentage of population for whom folic acid paradoxically blocks folate absorption, not taking FA is essentia”
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Not that I’m aware of.
More competent Naturopathic Docs of my acquaintance recommend against folic acid supplementation for all patients, regardless. If I were her, I’d drop anything with folic acid, including enriched flour. When I work with people who are suffering from chronic fatigue, this is one of the suggestions I always make.
For myself, I have taken folic acid (before I knew what it could do) at supplemental doses then recommended for people with my genetic mutations, and it was an horrific experience I hope never to repeat. I found out first hand that folic acid is nothing like bioavailable folate.
I’d say: pay the extra and get l-methylfolate or 5-methyltetraydrofolate. The latter is pretty cheap these days.
Direct message me if you want more specifics. Note I am USA-based, so what I can get might not be the same as what she can get.
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Yes, a standard DNA test should show you whether you have the MTHFR mutation which can mean you cannot methylate folate from folic acid. I discovered I had the mutation this way, it affects 10% of Caucasians and about 25% of Hispanics. However, if you take folate directly be very careful as it’s very easy to overdose. I won’t take more than 500mg per week for that reason.
Did you really mean 500mg/week? Or did you instead mean to type 500mcg/week?
Because 500mg per week is a significant amount–comes to about 71mg/day-- and if you’re taking that much, you’re way over the typical recommended dose, even for addressing deficiency.
Typical daily doses of folate (L-MTHF & L-5-MTHF) range from .5mg to 15mg/day, with 7.5mg and 15mg being common to address deficiency.
Cautions about taking too much folate need units and research citation. If you have sources for what you think constitutes an overdose, I’d be interested in seeing them.
My search today did turn up this:
The NOAEL [No-observed-adverse-effect level] for calcium L-methylfolate [L-5-MTHF] was 400 mg/kg bw/day.
Which is, frankly, much higher than I thought it would be. (If my math is right, for me that would be 24 grams of L5MTHF. Per day. Wow.)
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Dohhhh! Yes, you’re absolutely right. I am away from home at the moment and didn’t have my bottles to hand. What I should have said was 1000 micrograms per week, so roughly 140-150mcg per day. This is the product I use: https://www.amazon.co.uk/dp/B07V3RLXVQ/ref=pe_27063361_487055811_TE_dp_2
You will notice that it says 1000mcg is 500% of the recommended daily amount (that’s where I misremembered the figure of 500 from I suspect). So what I do is open one capsule and roughly divide it into seven doses to take over the course of the week.
Thank you for picking up my mistake.
Just as an addendum, I know Resveratrol doesn’t get much support around here, but this study showed it could be particularly beneficial in people with the MTHFR mutation
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Worth checking all antibodies too — a few years ago I suddenly started feeling awful without actually being sick, but hitting a brick wall, it felt like, with crippling fatigue. This came in the wake of a very stressful event so I thought it was mild depression but my family doctor ran a broad panel and it turned out I had mono. She checked for Lyme too but that wasn’t the case for me — it easily could have been to explain the symptoms.
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Recommend daily amounts have very little to do with healthspan. So I’ll respectfully disagree with you that 140mcg/day is much of a dose for bioavailable folate but I honor your choice.
As I said, typical daily doses of folate (L-MTHF & L-5-MTHF) range from .5mg to 15mg/day, with 7.5mg and 15mg being common to address deficiency.
I agree: it’s worth considering activated or re-actived EBV (mono) as a fatigue cause, too.
I’ve recently been working with reactived EBV and rapamycin, since rapamycin has a complicated relationship with viruses. This thread might be useful for you, too.
(Still experimenting, so I haven’t done a full post, but my most recent impressive success with addressing/countering reactivated EBV was using Andrographis (paniculata).)
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Perhaps I should experiment with higher doses then. However, some of the side effects of too much methylfolate sound quite worrying to me (severe anxiety, nausea, insomnia, migraines, irritability, achy joints, headaches) which is why I’ve been very careful with it personally. Clearly I shouldn’t have used the word overdose as that obviously has other connotations.
I found this article useful
https://www.mygenefood.com/blog/are-you-taking-too-much-methylfolate/#:~:text=Taking%20too%20much%20methylfolate%20can,joints%2C%20headaches%2C%20and%20more.
Exactly the same happened to me in 2019-2020 just before COVID hit : took such a long time finding diagnose here in Spain ( the specialist said she never had adult having this at over 40 
) ; I was just trying to hold on and on while feeling exhausted as they kept telling me it was psychological in absence of “ real “ ( they also made me take antibiotics against Lyme just in case 
even though test was negative ; it was better to be safe than sorry I was told as “ sometimes tests are negative and you could still have it; or you could just have picked it up “ anyway …
I somehow suspect I may have picked it up on Maldives holiday ( lack of hygiene in restaurant?) as I went purely on that holiday alone to take a week for myself ; only resting and reading and mild exercise , as I had been working so hard the months before (didn’t do anything else basically the year before) but weeks after I got back felt more and more tired. But who knows
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Perimenopause is certainly one possibility.
She needs assessment by a physician who understands endocrine and functional/anti-aging medicine.
I see these presentations multiple times weekly, the differential diagnosis is broad from hematologic, metabolic, endocrine, gut health, rheumatologist, cardiac, oncologic, and mental health issues - to name a few.
Feeling significant fatigue is certainly explained by dropping estrogen and progesterone — but there are a multitude of other possibilities. Time to not try and diagnose oneself as there is a method to working up such symptoms - seeing an expert who regularly sees and diagnoses such patients is the answer.
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I caught mine exactly at the same time period — right before COVID! I guess I was blessed with a good family doctor who cast a wide net with the test. I hadn’t even heard of mono until I found out I had it. Pretty sure I caught it at the hospital where I had stayed for 15 days with a sick child. Hospitals are Petri dishes of all sorts of infections.
Don’t you hate it when the physicians try to tell you it’s all in your head?
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Absolutely; you end up starting to believe it must be in your head. And of course the fatigue and plus medical visits where they repeat this don’t help. Luckily I didn’t take the anti-depressants that more than one doctor prescribed me… but I was lucky I got the diagnosis just on the day before closing all the hospitals and medical services here … I was told it is supposed to be a child - teenager disease 
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Iodine can be a key here too, worth doing some reading on it.
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Maybe also have Vitamin D checked? I don’t know how much sun she gets there.
I had unexplained fatigue years ago, and the only thing they found after extensive blood tests was low Vit. D. I finally got better after taking it for several weeks.
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This is what I do for a living: testosterone replacement
Testosterone therapy in women: Myths and misconceptions
https://www.maturitas.org/article/S0378-5122(13)00012-1/fulltext
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