Side Effects - Vitamin B6 and Paracetamol
Side effects
Following on from The Nuanced Naturopaths podcast on the subjects (ep. 44 and ep. 46). A topic that’s super relevant for anyone who’s ever taken a supplement or popped a painkiller: side effects or more correctly, ‘Adverse Drug Reactions’. Yes, those pesky little (or big) things that sometimes come along with our health remedies (pharmaceutical, herbal or otherwise). We’ll explore the buzz around Vitamin B6, and the concerns about paracetamol/acetaminophen, and why it’s essential to ask the right questions about what we put into our bodies.
Side effects, Vitamin B6 & Paracetamol
This article covers -
Understanding side effects
‘Natural’ and ‘Safe’ - are they the same thing?
The buzz around Vitamin B6
New concerns about Paracetamol (Acetaminophen)
Practical Tips for navigating Supplements and Medications
Understanding side effects
What are side effects? Correctly they are known as Adverse Drug Reactions (ADRs) and simply put, they are unintended actions of a medicine that are often undesirable.
Think about it, for a drug or herb or a supplement to change something in the body it needs to have an action, it needs to ‘do something’ - change something in the body, and so potentially anything that has an action can trigger a reaction. For the sake of ease I’m going to refer to all drugs, supplements, vitamins, minerals, herbs or mushrooms as ‘medicines’ in this article - which is technically correct, when the effect is desired. If the ‘action’ isn’t desired, it may be referred to as a ‘toxin’ or an ‘allergen’.
The way a medicine (or any chemical) moves through the body can be defined in one of two ways;
Pharmacokinetics - or what the body does to the medicine, including the way it is absorbed, its bioavailability, the distribution, how it is broken down (metabolism) and how it’s excreted.
Pharmacodynamics - what the medicine does to the body, including how and which receptors it binds to, and what effects that stimulates and chemical interactions (sometimes with other medicines).
This can influence how medicines interact with us, and how our bodies respond.
Types of reactions
Allergy - One kind of reaction may be an allergic reaction, where parts of the immune system respond to a molecule in the medicine - and technically ANYTHING can be an allergen. There are people in the world who have allergic reactions to water, cold temperature, vibration, touch or more commonly to allergens such as peanuts, milk, pollen or dust.
Genetic variations - Reactions may be due to one or more genetic variations (called a ‘snip’) resulting in the lack of a necessary enzyme, e.g. lactase - required for digesting lactose. This can also apply to all kinds of enzymes necessary for breaking down medicines in the liver meaning causing an excess or too little of the medicine in the bloodstream.
Gut microbiome interactions - Alterations to the gut microbiome/s can influence the way a medicine is absorbed. Some medicines (particularly pharmaceuticals) can disrupt the microbial species by changing the pH, or by killing or by supporting various microbes (good or bad), allowing them to overgrow. In killing some bacterial species the outer cell membrane can release toxins (endotoxins) causing inflammation, pain, headaches, and burden the liver. Antibiotics are non-selective killers of microbes - in other words, they kill bacteria indiscriminately, the bad, the good and those in between. In some cases, this can mean allowing other microbes e,g, fungal species like Candida spp. to overgrow.
Some medicines alter metabolism in ways that can cause higher blood sugar in areas such as the bladder or kidneys, triggering urinary infections. Some herbal medicines actually work by interacting with beneficial species of gut microbes, which then produce molecules that support the body’s healing. And a person who has a susceptibility to allergies might experience a reaction when a medicine triggers a release of histamine from gut microbe interactions.
‘Think about it, for a drug or herb or a supplement to change something in the body it needs to have an action, it needs to ‘do something’ - change something in the body - and so potentially anything that has an action can trigger a reaction.’
‘Natural’ and ‘Safe’ - are they the same thing?
There is a concerning, but understandable misperception that anything natural is therefore, safe. Sadly, this is not necessarily true.
Cyanide, arsenic, lead, and mercury for example, are all natural and most definitely NOT safe. Wheat is natural, but not safe for anyone with celiac disease. Psilocybin from magic mushrooms or THC from cannabis are natural but not safe to consume if you’re going to drive a car or operate machinery.
What is ‘natural’ exactly? I think it's safe to assume that when most people say something is natural they mean it's derived from a natural source. Most supplements, even the highest quality and most effective forms are usually synthetic versions of a natural molecule. This is to ensure that they are reproducible, stable, not affected by heat, moisture, time, oxidation or other chemical reactions that will change them so that they remain transportable and shelf-stable for as long as possible. There are a handful of supplements that contain vitamins and minerals derived from food sources such as Vitamin C extracted from Kakadu Plum, however, Vitamin C is inherently unstable and degrades easily with heat, time, and moisture. So, measures still need to be taken to ensure the quality is maintained.
Natural products can be safe. They can be safe in certain people, certain circumstances, or specific dosages but the two terms describe very different qualities and are not interchangeable.
As mentioned before, if a molecule causes an action in the body it has the potential for that to be a ‘reaction’. For a molecule to be 100% safe, it would need to have no action at all on the body, and for it to contribute to healing it needs to ‘do’ something.
Interactions - In some instances herbal medicines, or supplements can interact with the way a pharmaceutical drug works by causing more or less of the drug in the body - this can be potentially dangerous - but it doesn’t mean the herb or supplement themselves are harmful.
This can also happen with two pharmaceutical medicines. If you are unsure, herb-drug interactions can be checked by your naturopath (as they understand herbal medicine and a degree-qualified naturopath has completed at least one unit of pharmacology) and drug-drug interactions should be checked by your doctor and/or pharmacist.
‘Wonky’ research - On the other hand, some research on herbal medicines is of a very poor quality, with dosages and method of administration bearing little resemblance the way these herbs are used traditionally or by herbalists and naturopaths. In the past research was done by people who don’t necessarily understand herbal medicines, today naturopaths and herbalists are participating in or conducting this work and the results are very positive. Think about how this might change the results…if a herbal action is due to its interaction with the gut microbes, or their by-products then an experiment in a test tube is not going to be an accurate reflection, is it? Equally, administering huge quantities to laboratory animals to see how much is going to be harmful, does not reflect how it works in humans with proper dosing. Alternatively, some concerns about interactions with drugs are purely theoretical e.g. the actions of the herb and drug are similar or opposing and it’s hypothesised that this may cause a problem, without any research that proves it.
Online/overseas supplements - Another consideration around safety of medicines is the quality. In Australia the Therapeutic Goods Administration (TGA) evaluates, assesses and monitors all therapeutic goods. The TGA is recognised as having the most stringent regulations in the world, and ensures that products permitted for sale in Australia are safe. This can’t necessarily be said about products that are purchased online from other countries. This can mean that a product purchased from overseas may be:
Not what is stated on the label, or in the quantities stated
Substituted for something else (sometimes harmful substances, or pharmaceutical drugs)
Adulterated in some way
Poorly handled, meaning they are not clean, contaminated, mouldy, exposed to heat or moisture.
Not in therapeutic dosage - exceeding or insufficient to needs
To be sure of quality look for an AUST L or AUST R number on your product to determine if it’s approved by the TGA.
When buying supplements look for an ‘AUST L’ or ‘AUST R’ number on your product to determine if it’s approved by the TGA.
Cost - is another important consideration. If you don’t need a particular medicine, then taking it potentially is causing financial harm, while giving you no benefit. Herbs and supplements are not covered by Medicare so they can be expensive (imagine if pharmaceuticals weren’t covered!). Some really cheap supplements in supermarkets and chemists are of low quality (e.g. giant tubs of fish oil) or contain below therapeutic doses.
Dosage - Medicines of all kinds have recommended therapeutic dosages, which means there is evidence of them being safe and effective at that dose. More does not equal better. Sometimes, more equals an overdose and less may have little or no effect. Some require a level in the body before they become effective and so it can take time to notice a difference. A great example is magnesium - about 80% of the population is deficient in magnesium, and some people are very deficient. If you take too little (or the wrong form) it may take a long time before you become replete, and feel a difference, but if you take large doses it can cause diarrhoea, preventing its absorption. Some over-the-counter supplements contain a number of ingredients with differing names e.g. a herb usually has a common name “St Mary’s Thistle” or a latin name “Silybum marianum” or a Vitamin may be in a different form e.g. Vitamin B6 versus one of its other forms (see below). These alternate names can be confusing, meaning you can accidentally take more than intended over a number of supplements and cause a reaction.
The buzz around Vitamin B6
There has been a lot of discussion over Vitamin B6 and its safety. It’s a great demonstration of this discussion.
What is Vitamin B6?
Vitamin B6 is one of the water-soluble vitamins which is excreted in the urine, so it passes pretty quickly through the body.
It is not one, but a collection of similar molecules in different forms, each called ‘vitamers’. The 3 main B6 vitamers are;
Pyridoxal
Pyridoxine (Pyridoxol)
Pyridoxamine
And each of these forms comes in phosphorylated and non-phosphorylated forms.
The active form found in the body is pyridoxal 5’-phosphate (PLP) is necessary for over 100 enzymatic reactions, particularly in breaking down and utilising of proteins and protein components (amino acids), fat and carbohydrates. It is important for making neurotransmitters (mood chemicals) and blood, for blood glucose regulation, brain and immune function. Each of the forms is absorbed and transformed in different ways, requiring enzymes and other cofactors to make these changes.
Vitamin B6 is found in animal tissues in the form of PLP and pyridoxamine 5’- phosphate (PMP) and plants contain pyridoxine (PN) and pyridoxine 5’- phosphate (PNP). Common over-the-counter supplements contain synthetic forms of pyridoxine hydrochloride, pyridoxal 5-phosphate (PLP), and pyridoxal 5-phosphate monohydrate.
B6 toxicity
Reported in the media earlier this year (2025) was the fact that some people can have a reaction of peripheral neuropathy (tingling in the fingers and toes, potentially permanent if left untreated) from Vitamin B6 in excess doses, or after taking it for an extended period of time, and sometimes (rarely) even in small doses and short-term. In some, this was due to unknowingly taking it in multiple over-the-counter self-prescribed supplements (a good reason why you should see a practitioner to be prescribed accurately). One serious case was a GP who had been taking a supplement containing B6 for an extended period of time, unaware of the potential for this reaction/toxicity, and sadly the damage in her case appears permanent.
The TGA recommends the maximum daily dose as 100 mg/day for adults (previously 200 mg), with lower limits for children. However, cases of peripheral neuropathy have been reported at doses below this threshold and the European Food Safety Authority (EFSA) recommends a Tolerable Upper Intake Level (UL) as 25 mg/day.
Interestingly, peripheral neuropathy is also a symptom of Vitamin B6 deficiency and so B6 may be the treatment given. This is what is described in science as a U-shaped curve - too little is harmful, and so is too much.
Why does this happen and how can you tell if it will happen to you?
You can’t really tell if this will happen to you, unless you start taking it and notice the symptoms of tingling - in which case you stop taking it immediately and speak to a practitioner. It’s another good reason why supplements should be taken under the guidance of a practitioner. Sadly, there are no tests that show if you are at risk of B6 reaction or toxicity. If a close family member such as your parents or siblings has experienced a reaction it’s possible that there is a genetic link and you may need to exercise caution, too.
The reason this happens is related to how the various forms are broken down in the body to form the active PLP. Essentially, if for some reason;
genetics,
inflammation,
conditions that cause excess free radicals,
smoking,
mould or environmental chemical exposure
Then impacting the way some of the vitamers are metabolised, causing an excess of B6 vitamers that are damaging to the neural system - in some people. In this case, stopping the Vitamin B6 supplement will prevent further damage, however, this does not address the underlying issue and important to work with an experienced practitioner to identify and treat the root cause.
New concerns about Paracetamol (Acetaminophen)
Paracetamol (aka acetaminophen) is commonly known as the safest pharmaceutical drug. People will say, ‘I only take paracetamol…and only if I really need it’ demonstrating the perceived safety of paracetamol. It can be safe, provided it is taken exactly as directed; however, its perceived level of safety makes it potentially dangerous.
Paracetamol is safe, right?
When taken according to the dosage instructions, paracetamol is relatively safe however, there are some complications in calculating what a safe dose actually is. Factors such as liver disease, alcohol consumption, malnutrition or fasting, and certain medications can impact how paracetamol is broken down (metabolised). Most paracetamol is metabolised in the liver to non-toxic, water soluble compounds which are excreted via the kidneys, however, a small proportion is converted to a toxic molecule N-acetyl-p-benzoquinone imine (NAPQI) which is then rapidly detoxified by the livers’ own antioxidant glutathione. However, when glutathione levels are low, or paracetamol doses are high it becomes overwhelmed with the NAPQI which binds to liver cells causing them to die, triggering inflammation, liver damage and potentially liver failure and death. A treatment is available within 2-6 hours of ingestion, however, after that time there is no effective treatment.
Recently, worldwide restrictions around the sale of paracetamol have been made - reducing packaging sizes, slow-release products, claims made and reducing accessibility to large quantities. This is in an effort to reduce accidental and intentional paracetamol-associated acute liver failure and death. The rates of paracetamol poisoning increased from 2004 to 2017 by 77% and where treatment was delayed longer than 2-6 hours then around 5% of people who overdose, died. The TGA conducted a review in 2022 examining the safety of paracetamol in Australia finding that more vulnerable groups such as children and the elderly are at greatest risk of accidental overdose, and adolescents and young adults have higher incidence of intentional overdose. Slow or modified release paracetamol is harder to treat.
It is also interesting to note that a 2014 study published in journals including The Lancet revealed that for lower back pain paracetamol was ‘no better than placebo’. (Perhaps another time I’ll write about the conundrum that is the placebo effect). In fact, research shows it is still not clear how paracetamol works.
It’s also important to note that drug dosage calculations are based on the size of a person’s (healthy) liver, and therefore how well it will metabolise the drug. It’s pretty easy to understand that a tall, adult man is going to have a bigger liver than a baby or an elderly lady, but it’s not easy to calculate that from one individual to another. And ALL our organs are slightly different sizes and shapes - and even locations. Also, how efficiently our liver will metabolise a medicine depends on how healthy the liver is. In children and the elderly it can be difficult to determine the size of the liver or its health, because children grow at different rates for their age and the elderly may not have the liver function that they did in their youth. Accidental overdose can be a serious problem in the elderly and in children.
Paracetamol is often taken as the perceived safer alternative to nonsteroidal anti-inflammatory drugs (NSAIDs) like Ibuprofen, Nurofen, Naproxen, Aspirin, Diclofenac, Celecoxib or a myriad of other names. In some cases these medicines interact with other drugs and so they are contraindicated, meaning they are not safe to take together. A known adverse reaction occurring with NSAIDs is that they block a pathway called cyclooxygenase-2 (COX-2) which is responsible for some types of pain, and also responsible for maintaining the health of the stomach and gastrointestinal system. Meaning NSAIDs can cause gastric ulcers, stomach upset, abdominal pain and an increased risk of bleeding in people taking NSAIDs.
Considered the safer choice for oral, long-term pain relief, however a 2024 large study from the UK of over 582,000 people aged over 65 revealed that paracetamol DOES, in fact, block the same COX-2 pathway as NSAIDs, resulting in an increased risk of peptic ulcers, gastrointestinal bleeding, and also is associated with increased risk of heart failure, high blood pressure and chronic kidney disease. This is a significant finding and one that will change the course of chronic pain management, particularly in the older population. In the UK paracetamol is prescribed free-of-charge, but is also available for sale over the counter and the authors acknowledge that over the counter sales are not monitored, meaning that consumption was potentially higher than recorded. Nevertheless, its association with other very serious health conditions of hypertension (high blood pressure), chronic kidney disease and heart failure in this population is alarming, especially given its minimal effectiveness as an analgesic.
So, our safest drug is not as safe as we thought.
Kaur et al., (2024) - A new UK study found concerning adverse reactions associated with long-term paracetamol use.
Practical Tips for Navigating Supplements and Medications
How do you choose which supplements or medications you need? Are you trying to suppress symptoms, resolve nutrient deficiencies, treat the root cause or are you taking them because you were told it might help by a friend/relative/neighbour/influencer? How often do you choose to take something because you believe it is ‘generally healthy’ without any particular aim in mind?
We are all different, and two people can have identical symptoms with entirely different causes. What medicines or supplements you take will be influenced by what you are trying to achieve, and -
Other health conditions
Your general level of vitality
How well you sleep
The size of your body
Genetic factors
What you eat
Amount of stomach acid
What environmental chemicals you are exposed to
How much water your drink
Your age
What other medications or supplements you are taking
The health of your liver, spleen, kidneys, immune system
The make up and diversity of your gut microbiome
How well your digestive system is working
The amount of inflammation
How active you are
If you see products advertised or promoted and they look really persuasive, ask these questions:
Are they biased by financial gain? (i.e. it’s a product they will profit from)
Is backed by science, does the research apply to you or the product?
Does it consider your individual circumstances?
Is it safe with your current medications?
Where was it sourced?
Is it available in Australia? (and TGA approved)
Is the ingredient available from food, or lifestyle changes? (always the better choice)
What are the potential side effects?
How long do you intend to take it?
What results do you expect to see, and in what timeframe?
What is the quality of the product?
What is the appropriate dosage for what you are trying to achieve?
Are you already taking one/some of the ingredients in another supplement?
With all that needs to be considered, a practitioner with a degree is the person who is best qualified to filter all of the variables that impact your body, with your set of circumstances, to triage what is most important for you. Otherwise, you risk taking something that may be harmful or a waste of money.
Frequently asked questions -
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That is a very broad question, but one that’s commonly asked. My reply is ‘which supplement, in what dosage, at what frequency, to treat what symptom? If the supplement is a vitamin or mineral, you might be looking to treat a nutritional deficiency, and if it’s a herbal medicine then you might be trying to treat a specific symptom or collection of symptoms.
Supplements that are approved by the Australian Therapeutic Goods Administration (TGA) are generally safer than those bought from other countries, because the TGA has the most stringent safety regulations.
So, you need to be specific about what you are trying to achieve and whether you have the right product, in the right form, and the right dose.
Or, if you book in to see me I can go through all of your supplements with you and advise which should stay, and which you can do without - or make other recommendations.
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Vitamin B6 is the name given to a collection of molecules essential for around 100 different enzymatic reactions, particularly in breaking down and utilising (metabolism)of proteins and protein components (amino acids), fat and carbohydrates. It is important for making neurotransmitters (mood chemicals) and blood, for blood glucose regulation, brain and immune function. Each of the forms is absorbed and transformed in different ways, requiring enzymes and other cofactors to make these changes.
In high doses, or long term and in some rare cases in low doses, Vitamin B6 has been associated with tingling in the hands and feet which can become permanent if not treated. This adverse reaction does not occur in all people, but caution should be taken when buying supplements as the names of the various forms of B6 are different, and it can be easy to overdose by mistake.
It is an essential vitamin and not inherently harmful, but in some people with specific genetic predispositions, or taking other medications or other health conditions the way B6 is broken down can be impaired and cause nerve damage. For this reason, you should seek the help of a qualified practitioner for guidance on all supplements.
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Arsenic, mercury, lead, cyanide … are all natural, but they are not safe. Wheat is safe for most people but not for someone with celiac disease.
Most health supplements are produced synthetically to ensure that they remain stable for transport and don’t react to heat, moisture, or over time. They need to remain fresh and shelf-stable and still provide the action intended. Some supplements are derived from natural sources, but because of the inherent instability of some vitamins and minerals, some kind of treatment might be needed to ensure that they don’t degrade over time.
For any medicine (herbal, pharmaceutical or supplements) to work, it needs to perform an action on the body and if there is an action, there can be a reaction potentially. All medicines carry the risk of these reactions and when they are undesirable, unintended reactions are called Side Effects, or more accurately ‘Adverse Drug Reactions.
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If it is taken exactly as directed on the packet, for most people it is considered safe. Unfortunately, it’s not as safe as we used to think for everyone.
Package sizes and some forms of paracetamol (acetaminophen) have been changed worldwide, due to the risk of accidental or intentional overdose, resulting in serious liver damage and death.
Paracetamol is often taken as a safer alternative to non-steroidal antiinflammatory drugs (NSAIDs) as they are associated with damage to the lining of the stomach, stomach ulcers and cancers. It was thought previously that paracetamol did not use the same pathways and therefore didn’t cause these problems. HOWEVER, new research has discovered that it does use the COX-2 pathway and long term use is associated with stomach ulcers, and also with heart failure, kidney disease and high blood pressure.
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The best health supplement is the one you truly need, in the form that is best for your body, in the dosage that is applicable for you and for the length of time appropriate for the outcome you are trying to achieve.
Most supplements are synthetic versions of molecules that occur naturally, and many contain other ingredients (excipients) that keep it shelf stable, free flowing, preserved against moisture, oxidation or bacteria.
Australian supplements are regulated under the most stringent guidelines, so while online supplements might look good - you just don’t know that you are getting what you think you are (no matter how persuasive the advertising!).
The best way to know what your body needs is to speak to a naturopath who can prescribe you the most appropriate thing to address the root cause of your condition. Taking supplements long term can be expensive, and sometimes if you are taking too many, too much or the wrong supplement you may cause harm.
