Folate is critical

One of the B vitamins, known as folate or vitamin B9, is a critical nutrient in over 200 processes in the body, including the production of blood cells, chemical messengers in the brain, cleaning up waste products from the body and preventing the development of cancer.

The active form of this nutrient is produced in two ways: firstly, the body itself has a manufacturing process, utilising dietary sources, and secondly, healthy bacteria in the gut (known as the microbiome) can directly manufacture and supply folate for the body to use.

Some people have a genetic error (known as a SNiP) which disrupts the body’s own manufacturing process, but a healthy diet and healthy microbiome provide a perfect “work around” for this, producing the needed folate in the gut.

Tragically many things can disrupt these processes, including poor diet and several modern medicines, leading to critical depletion of folate for the body. Antibiotics, which kill off not only disease-causing bacteria but also the friendly folate-producing ones. And other drugs like Valproate which disrupt the utilisation of folate.

Uncovering the root causes of folate disruption, restoring a healthy diet and gut microbiome, and removing drugs that are hindering its utilisation are all crucial steps in recovery.

Folate-rich foods


Common symptoms of folate deficiency can include:

Tiredness, fatigue and lethargy
Muscle weakness
Neurological signs, such as a feeling of pins and needles, tingling, or burning, or peripheral neuropathy, i.e. a numbness in the extremities
Psychological problems, such as depression, confusion, memory problems, problems of judgement and understanding
Gastrointestinal signs, such as nausea, vomiting, abdominal pain, weight loss and diarrhoea
Headache and dizziness
Shortness of breath
Painful swallowing
A sore tongue (glossitis) and mouth ulcers
Petechiae (tiny, circular, non-raised patches that appear on the skin or in a mucous or serous membrane)
Angular stomatitis (fissures in the corners of the mouth)
Exfoliative dermatitis (a condition which makes the skin red and scaly)

Consequences of more serious folate deficiency can include:

Neural tube defects in the foetus
Fast heartbeat (tachycardia)
Fast breathing (tachypnoea)
Heart murmur
Heart disease
Megoblastic anaemia
Myelodysplastic Syndrome (MDS)
Cancer (especially colon cancer)

Antibiotics are by far and away the most common and widespread cause of folate deficiency! And some antibiotics are worse than others!

For example, one antibiotic called trimethoprim acts as a folate-antagonist  by inhibiting an enzyme called  dihydrofolate reductase, which is essential for the converting of folate into a form that the body can utilise. The inhibition of this enzyme can cause folate deficiency, no matter how much folate is in the diet or is taken in a supplement.

dihydrofolate reductase enzyme


A little more detail

So lets look at folate in a little more detail.  What is folate? And why is it so critical to health? Folate is a water-soluble B-complex vitamin that supports some of the body’s most vital functions, including the formation of red blood cells and the production of energy, the production of DNA and neurotransmitters and the detoxification of cells. It plays an important role in reducing homocysteine levels in the body  (homocysteine is an amino acid that has been linked to both cardiovascular disorders and degenerative brain disorders).

Folate is vital for mental health

Folate  is needed for appetite, digestion (hydrochloric acid production), protein and carbohydrate metabolism, antibody production, zinc metabolism. It is critical to the immune system and the methylation system. Serious and prolonged folate deficiency can lead to cancer of the bone marrow (myelodysplastic syndrome and leukaemia).

Genetic error

Those people who are likely to be most affected by folate deficiency are those who have a (fairly common) error on the MTHFR gene*** that impairs the body’s ability to convert the vitamin. Such people are particularly dependent upon the form of folate that is produced by helpful bacteria. And these are the people who are most likely to suffer the most serious consequences of antibiotics – either physical or mental or both.

***Methylenetetrahydrofolate reductase, or MTHFR, is an enzyme that breaks down the amino acids homocysteine and folate. The MTHFR gene that codes for this enzyme has the potential to mutate, which can either interfere with the enzyme’s ability to function normally or completely inactivate it.

The production of methyl folate is just one of many, many benefits of a healthy gut microbiome. The subject is vast – with major major health implications. Conversely the consequences of antibiotics and poor diet on the microbiome can be devastating to health – particularly where there are genetic errors.

To illustrate this

Folate deficiency during pregnancy can cause spina bifida. It is interesting to note that – while Ireland has a high incidence of the HTMFR genetic error, Italy has an even higher incidence of the same error. However, the incidence of Spina Bifida is higher in Ireland than in Italy. The difference is in the diet! The Mediterranean diet results in a very much more healthy gut microbiome – and therefore a greater source of folate produced is by beneficial gut bacteria.

This is called epigenetics

A tragic irony

The drug, Valproate, widely prescribed for bipolar, is a perfect example of a tragic irony! Folate is critical for mental health. Associations between folate status and mood have been known for some time, with folate deficiency considered a treatable cause of depression (bipolar and unipolar) and bipolar mania.  Valproate, however, actually causes/exacerbates folate deficiency!

The mechanism of this effect is uncertain. Possible mechanism include reduced absorption, prevention of release of folate from tissue stores, altered plasma protein binding, or increased folate metabolism in the liver.  Valproate can cause severe folate deficiency, no matter how rich in folate the diet is – or even if folate is taken as a supplement.

Mental problems can occur after a course of antibiotics has cut off the supply of folate produced by helpful bacteria.

Valproate is known to interfere with folate!
What an ironic and tragic vicious cycle!

The fact that Valproate causes folate deficiency is well recognised. Valproate is highly teratogenic  and evidence supports that the use in pregnancy can lead to neurodevelopmental disorders and congenital malformations – those same disorders that can be caused by folate deficiency in pregnant women. That’s why valproate is contra-indicated in women of child-bearing age.

And yet the other side effects of Valproate-induced folate deficiency are less recognised.

Bone marrow suppression

For example – by interfering with the utilisation of folate, Valproate can cause  bone marrow suppression leading to aplastic anaemia or peripheral cytopenia affecting one or more cell lines. Occasional fatal bone marrow failure, myelodysplasia, and a clinical picture resembling acute promyelocytic leukemia have also been seen.


bone marrow suppression


Other possible side effects of Valproate:-

Abdominal pain; agitation; alopecia; anaemia; abnormal behaviour; impaired concentration; confusion; deafness; diarrhoea; drowsiness; haemorrhage; hallucination; headache; hepatic disorders; hypersensitivity; hyponatraemia; memory loss; menstrual cycle irregularities; movement disorders; nail disorder; nausea; nystagmus; oral disorders; seizures; stupor; thrombocytopenia; tremor; urinary disorders; vomiting; weight increased

Androgenetic alopecia; angioedema; bone disorders; bone fracture; bone marrow disorders; coma; encephalopathy; hair changes; hypothermia; leucopenia (low white blood cell count); pancreatitis; paraesthesia; parkinsonism; peripheral oedema; pleural effusion; renal failure; SIADH; skin reactions; vasculitis; virilism

Agranulocytosis; cerebral atrophy; cognitive disorder; dementia; diplopia; gynaecomastia; hyperammonaemia; hypothyroidism; infertility male; learning disability; myelodysplastic syndrome; nephritis tubulointerstitial; polycystic ovaries; red blood cell abnormalities; rhabdomyolysis; severe cutaneous adverse reactions (SCARs); systemic lupus erythematosus (SLE); urine abnormalities

Worth remembering

It is worth remembering that folate deficiency can occur even without prescribed drugs like Valproate. However, the above list of side effects of folate-depleting Valproate could just as well serve as a list of folate-deficiency symptoms. These side effects indicate just how critical folate is to so many bodily systems. And antibiotics are by far and away the most common and widespread cause of folate deficiency!


Click here  to read about a natural alternative to antibiotics that won’t kill off the folate-producing helpful gut bacteria.

Neem helps boost your immune system. It possesses anti-bacterial, anti-viral and anti-fungal properties. Neem also has blood-purifying properties, which allow it to clear toxins and impurities from the blood leaving you with a strengthened immune system.


Click here to read about how kefir can repopulate the gut with helpful bacteria

Kefir is a traditional food that has been attributed with exceptional health promoting and curative properties since the beginning of recorded history. It is a  fermented milk beverage, rich in protein, calcium, vitamin B12, niacin, and folate. Consuming kefir can boost the immune system, alleviate symptoms of diarrhoea and chronic constipation, and lower the risk of colon cancer


I will destroy the wisdom of the wise, and bring to nothing the intelligence of the intelligent . . . Has not God made foolish the wisdom of this world?” (1 Cor 1:19-20)

Heavenly Father, have we become blinded by science and pharmacy that we cannot see your wisdom at work here – “bringing to nothing” the “intelligence” of drug-based medicine? We are “fearfully and wonderfully made“. Yet we have foolishly overridden your provision for us – by destroying our microbiome  – with dreadful consequences! Give us eyes to see and understand, we pray, how much better are your ways. Amen


References nutrient-depleting drugs:

See:-  Hematologic toxicity of valproate

Hepatotoxicity is the most widely recognized toxicity. Valproate can cause direct bone marrow suppression leading to aplastic anemia or peripheral cytopenia affecting one or more cell lines. Occasional fatal bone marrow failure, myelodysplasia, and a clinical picture resembling acute promyelocytic leukemia have also been seen.

See:- Myelodysplastic syndrome associated with chronic valproic acid therapy

Valproic acid, used in the management of seizure and mood disorders has been reported to induce a reversible myelodysplastic-like syndrome associated with cytopenias. However, there are rare reports of patients on long-term valproic acid therapy developing acute myeloid leukemia with multilineage dysplasia and cytogenetic findings consistent with therapy-related acute myeloid leukemia

See:- Drugs and folate metabolism

A number of drugs such as aminopterin, methotrexate (amethopterin), pyrimethamine, trimethoprim and triamterene act as folate antagonists and produce folate deficiency by inhibiting the dihydrofolate reductase enzyme

See:- Considerations when prescribing trimethoprim

More than 40 years of widespread use has provided ample opportunity to identify the many adverse events associated with trimethoprim–sulfamethoxazole. Although this drug is well tolerated by many patients, it is associated with several potentially serious adverse reactions.  Many of these adverse effects are rare, however others are predictable and several can be life-threatening.


See also:- Seven Important Nutrients Depleted By Psychiatric Drugs

Studies show that pharmaceutical drugs can deplete your body of critical nutrients through multiple mechanisms, including increased excretion of vitamins and minerals, and impaired digestion, absorption and storage of nutrients.

Over time, nutritional deficiencies can develop. And these deficiencies can cause additional symptoms and increase the side effects. In fact, many drug “side effects” are simply nutritional deficiencies.