EP.287/ Low folate and endometriosis
Okay, today we’re continuing our theme of nutrient deficiencies that can disguise themselves as endo related problems.
And today, we’re talking about B9, otherwise known as folate.
So let’s dive straight into some of the signs to look for and how they may mimic endo related issues and symptoms…
Irritability and mood swings
One of the earlier signs of folate deficiency may be irritability and mood swings. Just like vitamin B12, folate is involved in the production of feel-good neurotransmitters like serotonin and dopamine. It is also involved in the health of our brain neurons, which are responsible for behaviour and emotional regulation and when damaged and impaired, can create behavioural changes.
Additionally, as you’ll come to learn shortly, folate deficiency also causes fatigue and low energy, which often can cause us to feel snappy and irritable.
I’m sure many of us can relate to feeling angry, irritable, and short tempered, especially if we’re in pain, tired or experiencing hormonal issues that I tend to see with clients, like low progesterone. However, if you notice this symptom a lot or you find it to be increasing, it’s important not to dismiss them as down to endo and hormones alone and to check your folate status.
Extreme fatigue
The fatigue with folate may start as feeling tired a lot and weak, and as the deficiency worsens, it can progress into extreme fatigue, which can easily be mistaken for being endo related.
Folate deficiency is linked to mitochondrial dysfunction. Mitochondria are like the generator in our cells, each cell, is essentially fed by the mitochondria, which takes energy from food and converts it into something called ATP. When folate levels decline, this can lead to less ATP output, resulting in less energy.
Additionally, folate is essential for the production of red blood cells, when these decline, we end up being less able to transport oxygen around the body. Eventually, we develop a type of anaemia called megaloblastic anaemia. This is when the body struggles to make fully developed red blood cells, and instead, forms large yet undeveloped cells called megablasts, which are incapable of carrying and delivering oxygen properly around the body. So, the end result is the same as iron deficiency anaemia, but how it lowers oxygen levels is different.
Cognitive function problems
Folate deficiency may manifest (and often does) as brain fog, difficulty concentrating, poor memory, etc. There are a few reasons behind this.
The first is that folate deficiency has been linked to oxidative stress and inflammation in the brain (oxidative stress is a really another conversation for another time but think of it as your cells rusting and degrading). These two problems can cause issues with the way the brain functions, such as impairing the signalling pathways that your neurotransmitters travel on and damage to brain neurons, which are essential to cognitive function. Think of signalling pathways as the train route, so say London to Glasgow, and the tracks are the neurons, whilst your neurotransmitters are the train. The station is the cell receptor, which, when the train arrives, will trigger a reaction from the cell, just like people getting off a train.
However, your brain neurons can also be damaged another way. Folate plays a lead role in the production and repair of DNA. Neurons, require high levels of DNA production and repair to function properly. When folate levels are inadequate, these processes may be affected, potentially leading to neuronal damage and impairments in brain function.
As we’ve discussed already, folate plays a key role in the production of neurotransmitters, which when lowered, can create feelings of lethargy, lack of motivation, difficulty concentrating and memory problems.
Finally, if you do develop folate-deficiency anaemia, your brain will be receiving less oxygen, resulting again in impaired function.
Dizziness
Next up is dizziness. So, the neurons and signally pathways I just spoke about, are also essential to a properly functioning nervous system. Your nervous system is responsible for voluntary actions like taking a step forward, but also involuntary actions too, like breathing. When this gets impaired and damaged, it can result in dizziness.
Of course, having anaemia and the resulting low oxygen levels can also result in dizziness.
There may also be some link with orthostatic hypotension, which is a drop in blood pressure upon standing, which manifests as feeling dizzy or faint. However, the evidence for B12 def and orthostatic hypotension is much stronger, and in some cases, these two deficiencies occur together and so, the orthostatic hypotension could really be down to B12 deficiency.
As we’ve now discussed many times on the show, endometriosis is being associated more and more with dysautonomia and POTS, two conditions that can cause dizziness. Many endo patients are seeking a diagnosis for these conditions when deficiencies may be at play alongside or instead of dysautonomia. Typically, the pathway to diagnosis of POTS or dysautonomia should rule out folate, B12, vitamin D and iron deficiencies as they can all manifest as symptoms of dysautonomia.
Palpitations
Palpitations can occur with folate deficiency due to the lack of oxygen supply, which can trigger the heart to beat faster as it works to get more oxygen to our cells and tissues.
Additionally, when folate goes down, homocysteine levels go up. Homocysteine is a naturally occurring amino acid which is produced when protein is broken down in the body, normally folate plays a key role in converting it into other substances, but when levels of these nutrients lower, homocysteine levels rise. High levels can cause oxidative stress and inflammation which damage the cardiovascular system and can lead to dysfunction.
However, if you do have palpitations and folate def, don’t panic – it’s most likely down to the anaemia as the cardio damage occurs with prolonged deficiencies.
As we discussed earlier, these palpitations may be put down to POTS or dysautonomia, but often, doctors can dismiss these as anxiety, especially if you have endo and experience chronic pain, as many doctors will assume you’re depressed or anxious as a result (though both of these are associated with endo).
Trouble breathing
Finally, another one I wanted to raise is trouble breathing. Folate deficiency, like B12, can lead to neurological problems, meaning the functioning of the nervous system, which regulates processes in the body like breathing, becomes impaired.
Additionally, as you’ve probably guessed, folate deficiency anaemia can also cause breathing difficulties.
This symptom, just like palpitations, can often be put down to anxiety or POTS, both of which affect our community.
Other symptoms worth being aware of are:
· Pale skin
· IBS symptoms
· A red, sore, and smooth tongue and mouth ulcers
· Cold hands and feet
I’ve linked to a few evidence based articles on folate deficiency symptoms you can refer to in the show notes.
Causes
So, there are a number of causes of folate deficiency, but I wanted to mention the ones related to endo the most.
Restrictive diets due to stomach upset
Folate comes from foods like fruits and veggies, beans, and organ meats like liver and one of the most common causes of folate deficiency is not eating enough of these foods.
Of course, an unhealthy diet rich in processed and packaged foods and low in veg, fruit, etc. would be one explanation, but in terms of our community, I often see people restricting these foods due to IBS issues.
People with endo are more likely to have small intestine bacterial overgrowth and general GI problems, which can lead them to restrict foods that can exaggerate symptoms, which is often foods rich in fibre like, yes, you know what’s coming – fruits, veg and beans.
If you’re having stomach issues which is causing you to restrict these healthy foods, my first piece of advice would be to begin working on your gut health. It doesn’t have to be complicated either! Yes, in the cases I work with, we do tend to have to work on SIBO, but not everyone will need to go that far. I’ve linked to some resources in the show notes if you want to start addressing your gut health problems.
Coeliac disease
Next up is coeliac disease, an autoimmune disease where gluten triggers the immune system to attack and damage the small intestine. This in turn lowers our ability to absorb nutrients, and so nutrient deficiencies can occur and in fact, B12, folate, vit D, vit B6, iron, copper and zinc are all common deficiencies in undiagnosed or untreated coeliac patients.
People with endo have an increased risk of coeliac disease, and the symptoms of coeliac disease are not always obvious, so I encourage you to have a listen of my coeliac disease episode, which I’ve linked in the show notes.
Birth control
Yep, this might be a surprising one, but oral contraceptives have been shown to deplete folate levels, as well as B12, selenium, vit C, zinc, B2 and B6. What’s very frustrating about this is that a number of these are antioxidants, which help us to fight oxidative stress. People with endo have lower levels of antioxidants and higher levels of oxidative stress, which contributes to endometriosis progression and symptoms. If an endo patient chooses to use birth control to help manage endo symptoms (remember, it’s not a cure), then at the very least, they should be made aware of these risks and recommended to supplement. In fact, supplementation for anyone using BC is advised by The European Review for Medical and Pharmacological Sciences.
Additionally, people with endo are more likely to have gut issues that impair absorption of nutrients, so coupled with birth control, you can see why it’s particularly important to be aware of this risk and increase food intake, perhaps supplement, get regular testing of folate and address root causes where required.
MTHFR gene mutation
Finally, let’s talk about the MTHFR gene mutation variants. These variants are relatively common in the general population. The MTHFR gene provides instructions for making the MTHFR enzyme, and this enzyme converts folate found in plant foods into its usable form. There are a number of mutations of this gene, which can lead to an impairment in the enzyme, resulting in less usable folate in the body.
Testing
So, let’s talk about testing.
The obvious test for folate is folate blood test, which your doctor should be able to readily do. However, there are problems with just doing this test. Most blood tests are looking at your total folate, which includes both the active form and inactive form. You may have plenty of inactive folate in the body, but if your body is having trouble converting it, then you may have low levels of the active (usable) folate. So, if your levels come back normal but you’re showing signs of folate deficiency, I would do a few other tests –
Firstly, rule out iron, B12 and vitamin D deficiencies because they can look a lot like folate deficiency.
It can also be helpful do a Complete Blood Count, which could indicate megaloblastic anaemia (caused by folate deficiency) if your MCV is high, which means your red blood cells are enlarged.
You could also check your homocysteine levels, which would be high with folate deficiency.
There is also the red blood cell folate test, which looks at folate levels in your red blood cells and can indicate a folate deficiency if low.
Finally, there is the methylmalonic acid test. Methylmalonic acid is a by-product of folate and B12 metabolism and so this test could give you a clue into whether you may have problems converting folate into its active form (in which case, it would be worth doing the MTHFR gene test) and can also indicate B12 or folate deficiency.
Okay, so what are you looking for on your test results?
For a standard folate blood test, optimal levels are more than 8 micrograms per litre. There is varying advice on this but testing after an 8 hour fast may give more accurate results but check in with your doctor or the lab you’re ordering with.
The other tests will provide you with reference ranges and it will be clear if levels are elevated for your MCV and homocysteine and if your methylmalonic acid levels are low.
In terms of supplementing, it’s of course always best to start with food sources of folate and I’ve linked to a great evidence-based article of folate rich foods but we’re looking at increasing veggies, fruits, nuts, seeds, beans and pulses and organ meats if you can hack it. If you know you have the MTHFR gene mutation, it would be worth increasing your intake of liver and eggs, which contain the active form of folate which your body does not have to convert.
Supplement wise, in Functional Medicine, we use about 400mcg per day, but more may be required for those with an MTHFR gene mutation or who are pregnant. The NHS state that taking 1mg or less per day is unlikely to cause harm.
When looking for supplements, try to avoid supplements with folic acid, which is a synthetic form and is not easily absorbed by the body. Instead, you can use folinic acid which is an unmethylated but easy to absorb natural form of folate, or you can use a methylated form, called L-methylfolate. Some people, even those with the MTHFR gene, cannot tolerated methylated folate as it can cause over stimulation, nervousness, anxiety, etc. If that is you, folinic acid could be a good option.
Of course, we don’t want to just supplement our way out of the problem. If you have a deficiency, it’s important to improve those levels but also work out why.
Additionally, always consult your doctor or healthcare practitioner when adding new supplements.
Show Notes
Folate deficiency symptoms
https://www.nhs.uk/conditions/vitamin-b12-or-folate-deficiency-anaemia/
https://www.healthline.com/health/folate-deficiency
Heart attack and serious allergic reaction symptoms
https://www.nhs.uk/conditions/anaphylaxis/
https://www.bhf.org.uk/informationsupport/conditions/heart-attack/signs-and-symptoms-of-heart-attacks-in-women
Gut heath and SIBO
https://www.theendobellycoach.com/podcast/10-root-causes-of-bloating-with-endometriosis-endo-belly-ibs
https://www.theendobellycoach.com/podcast/what-is-the-endo-belly-endometriosis-ibs
https://www.theendobellycoach.com/podcast/endo-belly-treatment-endometriosis-ibs
https://www.theendobellycoach.com/podcast/endo-belly-treatment-endometriosis-ibs
https://endometriosis.net/clinical/stress-gut-stomach
https://www.theendobellycoach.com/podcast/endo-belly-coeliac-disease?rq=coeliac
POTS/dysautonomia
https://www.theendobellycoach.com/podcast/pots-dysautonomia-with-endo?rq=POTS
https://www.theendobellycoach.com/podcast/endo-and-dysautonomia?rq=POTS
https://www.theendobellycoach.com/podcast/endometriosis-and-ehlers-danlos-syndrome?rq=POTS
Coeliac disease
https://www.theendobellycoach.com/podcast/endo-belly-coeliac-disease?rq=coeliac
Birth Control
https://www.europeanreview.org/article/4579
Folate rich foods
https://www.healthline.com/nutrition/foods-high-in-folate-folic-acid#3.-Eggs
Supplementing
https://www.nhs.uk/conditions/vitamins-and-minerals/vitamin-b/
Tests
Homocysteine - if levels of this are high, it'll indicate B12 and/or folate are low
Methylmalonic acid - early indicator of low B12
MTHFR gene variants - common mutation which you do'n’t need to worry about or test unnecessarily, but if you’re having trouble with B12 and folate as described in the episode, you may want to test.
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