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Vitamin B6, Magnesium and Autism Ranking: Insufficient/Mixed evidence

Vitamin B6 capsules

Vitamin B6 (also known as pyridoxine) is a water-soluble vitamin found in many foodstuffs including meat, fish, eggs, potatoes, beans, nuts and cereals.

It has several important functions, including allowing the body to use and store energy from protein and carbohydrates in food. It also helps to form haemoglobin, the substance that carries oxygen around the body.

Magnesium is a mineral found in many foods, such as leafy vegetables, grains and nuts, as well as meats and dairy products.  It activates enzymes, contributes to energy production, and helps regulate calcium levels, as well as copper, zinc, potassium, vitamin D, and other important nutrients in the body. 

Some people have suggested that some individuals on the autism spectrum do not have enough vitamin B6 and that this can lead to a wide range of difficulties (such as difficulties with social communication and social interaction).

Some people believe that that those difficulties can be overcome by eating more foodstuffs that contain vitamin B6 or by taking vitamin B6 supplements. Magnesium supplements are sometimes taken at the same time as the vitamin B6 supplements to counteract the side effects of the vitamin B6.

Our Opinion

It is unclear whether most individuals on the autism spectrum do or do not have a deficiency of vitamin B6. It is also unknown whether a vitamin B6 deficiency can cause or worsen symptoms (of autism or related issues) or arises because of autism, or is completely unrelated to autism. 

There is a reasonable amount of low-quality research (11 group studies and two single-case design studies with three or more participants) into the use of vitamin B6 and magnesium supplements as an intervention for individuals on the autism spectrum.

However, because the quality of that research is so poor, we cannot determine whether vitamin B6 and magnesium is likely to provide any benefits to anyone on the autism spectrum. We must wait for further research of sufficiently high quality to be completed.

There is a need for further research into the use of vitamin B6 and magnesium supplements for people on the autism spectrum.  Specifically, there is a need for studies which use robust methodology, for example, large-scale, placebo-controlled, randomised, double-blind trials carried out on several sites. 

That research should also identify which individuals are most likely to benefit from which formulations and dosages; should determine if vitamin B6 and magnesium supplements can be used as one of the elements within comprehensive, multi-component, treatment models; should compare vitamin B6 and magnesium supplements with other interventions which are designed to achieve similar results, such as special diets.

That research should also identify if vitamin B6 and magnesium supplements have any beneficial or harmful effects in the medium to long term. It should also involve people on the autism spectrum in the design, development and evaluation of those studies. 

There is some evidence that taking excessive amounts of vitamin B6 and magnesium supplements can result in potentially harmful effects, such as nerve damage to the arms and legs, hands and feet.

Because of this, we cannot recommend the use of these supplements. If you are taking any kind of dietary supplements you should follow guidance on their usage from the appropriate organisation in your own country (such as the Food Standards Agency in the UK or the Office of Dietary Supplements in the USA).

Disclaimer

Please read our Disclaimer on Autism Interventions


Audience

Some people believe people on the autism spectrum are deficient in a range of vitamins and minerals, including vitamin B6.

For example, Cornish (1998) reported that “Nutrient intakes on analysis fell below reference nutrient intake (RNI) levels for 53% (nine) children in one or more of the following nutrients: vitamin C, iron, vitamin D, niacin, riboflavin, vitamin B6, calcium and zinc. “

Some people also believe that those deficiencies can be overcome by eating more foodstuffs that contain vitamin B6 or by taking vitamin B6 supplements.

For example, Rimland (1987) stated “At the end of the four-month trial it was clear that vitamin B6 was the most important of the four vitamins we had investigated, and that in some cases it brought about remarkable improvement. Between 30% and 40% of the children showed significant improvement when the vitamin B6 was given to them.”

However we believe that it is unclear whether individuals on the autism spectrum do or do not have a deficiency of vitamin B6. For example, intakes falling below the RNI aren’t the same as being deficient, and don’t necessarily indicate an inadequate intake. It is also unknown whether a vitamin B6 deficiency can cause or worsen symptoms (of autism or related issues) or arises because of autism, or is completely unrelated to autism

Aims and Claims

Aims

Some people think that taking vitamin B6 with or without magnesium may help children and young people on the autism spectrum overcome a variety of problems, such as difficulties with social communication and social interaction.

Claims 

There have been various claims made for the use of vitamin B6 and magnesium supplements as an intervention for children and young people on the autism spectrum. For example, 

  • Barthélémy et al, 1981 claimed vitamin B6 supplements combined with magnesium produced improvements in social interaction and social communication, as well as improvements in reactions to the environment, in 21 children on the autism spectrum aged three to sixteen.
  • Kuriyama, S. et al, 2002 claimed that vitamin B6 supplements produced a significant increase in verbal IQ scores in 4 children on the autism spectrum aged six to 17.
  • Menage et al, 1992 claimed that vitamin B6 supplements combined with magnesium produced improvement in “…certain autistic symptoms (lack of interest in people, abnormal eye contact, impairment in verbal and non-verbal communication)” in five boys on the autism spectrum aged four to seven.

Key Features

Vitamins and minerals are essential nutrients that our bodies need in small amounts to work properly. They are found in many foods but can also be taken as supplements which come in a variety of forms, such as tablets and drops.

Vitamin B6, also known as pyridoxine, is a water-soluble vitamin. It is one of the B vitamins that is part of the vitamin B complex. It is found in most foods including beans, nuts, legumes, eggs, meats, fish, whole grains, and fortified breads and cereals.

Magnesium is a mineral found in many foods, such as leafy vegetables, grains and nuts, as well as meats and dairy products.  It activates enzymes, contributes to energy production, and helps regulate calcium levels, as well as copper, zinc, potassium, vitamin D, and other important nutrients in the body. 

Some people have suggested that when individuals on the autism spectrum do not have enough vitamin B6 they should take very substantial doses of vitamin B6 supplements. Magnesium supplements are sometimes taken at the same time as the vitamin B6 supplements to counteract the side effects of the vitamin B6. Those side effects may include nausea and cramping.

However, The Committee on Toxicity of Chemicals in Food, Consumer Products and the Environment (COT) in the UK and the Office of Dietary Supplements (ODS) in the USA both advise caution and have published guidance for the consumption of vitamin B6 and magnesium. For example, the COT made the following recommendations in 2003,

“Recommended intakes of pyridoxine are based on protein intake. In the UK, the RNI [Reference Nutrient Intake] is set at 15 g/g protein for adults. This is equivalent to approximately 1.4 and 1.2 mg/day in the UK for males and females respectively. In the US, the Recommended Daily Allowance is set at 1.3 mg/day, and it is approximately 1.6 mg/day in Australia. Pregnant and lactating women and older people, who have low vitamin B6 levels, can usually increase their intake through a high-protein diet.”

For the latest information on their recommendations please see The Committee on Toxicity of Chemicals in Food, Consumer Products and the Environment website at https://cot.food.gov.uk/ and the Office of Dietary Supplements website at https://ods.od.nih.gov/ 

 

Cost and Time

Cost

The cost of using vitamin B6 and magnesium supplements will depend on a number of factors including the supplier, the brand, the dosage, and the length and frequency of treatment.

We found a wide range of suppliers providing vitamin B6 and/or magnesium supplements for a wide range of prices when we did an online search on 29 May 2018. Prices for vitamin B6 varied from £5.49 for 100 50 mg tablets to £7.12 for 100 250 mg tablets. Prices for magnesium varied from £4.19 for 90 300 mg tablets to £13.46 for 120 100 mg tablets.

Time

The amount of time it takes to use vitamin B6 and magnesium supplements will depend on a number of factors including the overall length of treatment, the frequency of treatments and the time taken to administer a single dose, as well as the needs of the person undertaking it.

In most cases, vitamin B6 and magnesium supplements are taken daily or twice daily, often before mealtimes.

 

Risks and Safety

Hazards

All vitamins and minerals can be hazardous in incorrect doses, and some may interact dangerously with medications already being taken. Therefore, professional advice should always be obtained before embarking on a course of vitamin or mineral supplements.

According to the US Office of Dietary Supplements factsheet on vitamin B6 (2018),

“High intakes of vitamin B6 from food sources have not been reported to cause adverse effects. However, chronic administration of 1–6 g oral pyridoxine per day for 12–40 months can cause severe and progressive sensory neuropathy characterized by ataxia (loss of control of bodily movements). Symptom severity appears to be dose dependent, and the symptoms usually stop if the patient discontinues the pyridoxine supplements as soon as the neurologic symptoms appear. Other effects of excessive vitamin B6 intakes include painful, disfiguring dermatological lesions; photosensitivity; and gastrointestinal symptoms, such as nausea and heartburn.”

According to the US Office of Dietary Supplements factsheet on magnesium (2018),

“Too much magnesium from food does not pose a health risk in healthy individuals because the kidneys eliminate excess amounts in the urine. However, high doses of magnesium from dietary supplements or medications often result in diarrhea that can be accompanied by nausea and abdominal cramping. Forms of magnesium most commonly reported to cause diarrhea include magnesium carbonate, chloride, gluconate, and oxide. The diarrhea and laxative effects of magnesium salts are due to the osmotic activity of unabsorbed salts in the intestine and colon and the stimulation of gastric motility.

“Very large doses of magnesium-containing laxatives and antacids (typically providing more than 5,000 mg/day magnesium) have been associated with magnesium toxicity, including fatal hypermagnesemia in a 28-month-old boy and an elderly man. Symptoms of magnesium toxicity, which usually develop after serum concentrations exceed 1.74–2.61 mmol/L, can include hypotension, nausea, vomiting, facial flushing, retention of urine, ileus, depression, and lethargy before progressing to muscle weakness, difficulty breathing, extreme hypotension, irregular heartbeat, and cardiac arrest. The risk of magnesium toxicity increases with impaired renal function or kidney failure because the ability to remove excess magnesium is reduced or lost”

Contraindications

There are some contraindications (something which makes a particular treatment or procedure potentially inadvisable) for some people. 

According to the US Office of Dietary Supplements factsheet on vitamin B6 (2018),

  • “Vitamin B6 supplements might interact with cycloserine (Seromycin), an antibiotic used to treat tuberculosis, and worsen any seizures and nerve cell damage that the drug might cause.
  • Taking certain epilepsy drugs could decrease vitamin B6 levels and reduce the drugs’ ability to control seizures.
  • Taking theophylline (Aquaphyllin, Elixophyllin, Theolair, Truxophyllin, and many others) for asthma or another lung disease can reduce vitamin B6 levels and cause seizures.”

According to the US Office of Dietary Supplements factsheet on magnesium (2018),

  • “Bisphosphonates, used to treat osteoporosis, are not well absorbed when taken too soon before or after taking dietary supplements or medications with high amounts of magnesium.
  • Antibiotics might not be absorbed if taken too soon before or after taking a dietary supplement that contains magnesium.
  • Diuretics can either increase or decrease the loss of magnesium through urine, depending on the type of diuretic.
  • Prescription drugs used to ease symptoms of acid reflux or treat peptic ulcers can cause low blood levels of magnesium when taken over a long period of time.
  • Very high doses of zinc supplements can interfere with the body’s ability to absorb and regulate magnesium.”

If you have concerns about your diet or your child’s diet, you should seek advice from a responsible health professional such as a GP or pharmacist. This may lead to a referral to a dietitian, in particular one with experience of working with individuals on the autism spectrum.

Notes

Acid reflux (burning feeling in the chest caused by stomach acid travelling up towards the throat); dermatological lesion (abnormal lump, bump, ulcer, sore or coloured area on the skin); diuretics (medications designed to increase the amount of water and salt expelled from the body as urine); gastric motility (movements of the digestive system); heartburn (another term for acid reflux); hypermagnesemia (high level of magnesium in the blood); hypotension (low blood pressure); ileus (lack of movement somewhere in the intestines); neuropathy (damage to the nerves in the arms and legs, hands and feet); osmotic (tendency of a fluid to pass through a membrane into a solution where the solvent concentration is higher); photosensitivity (sensitivity to light); nausea (feeling sick); osteoporosis (condition in which bones lose their strength); peptic ulcers (open sores that develop on the lining of the stomach); renal function (kidney function).

Suppliers and Availability

Suppliers 

Vitamin and mineral supplements are available from a wide range of suppliers including health food stores, chemists and pharmacies, professional health care providers and online stores. 

If you are contemplating taking any kind of dietary supplement, you should seek advice from a GP, pharmacist or dietitian. The British Dietetic Association has information about qualified dietitians in the UK.

Credentials

There are no formal, internationally validated registered qualifications for most people who provide dietary supplements.   
However, in the UK, the quality of dietary supplements is regulated by the Medicines and Healthcare Products Regulatory Agency, if they ‘contain a pharmacologically active substance or make medicinal claims (claims to treat or prevent disease, or to interfere with the normal operation of a physiological function of the human body) ...’

In the UK certain supplements are considered to be foods and will therefore be regulated under general food laws by the Food Standards Agency and Department of Health. Others will be regulated as a medicine by the Medicines and Healthcare Regulatory Agency (MHRA).

All herbal medicines placed on the UK market must have a Traditional Herbal Registration (THR) or a marketing authorisation (previously known as a product licence). The MHRA now defines individual herbal medicines as either registered traditional herbal medicines or licensed herbal medicines.

In the USA dietary supplements are not classed as drugs, but the Food and Drug Administration is responsible for taking action against any unsafe dietary supplement product after it reaches the market. 

History

According to Nye et al (2005),

“The use of mega-vitamin intervention began in the early 1950s with the treatment of schizophrenic patients. Pyridoxine (vitamin B6) was first reported to improve speech and language in some children diagnosed with "autism syndrome" when Bönisch observed that some participants showed improvement in speech and language. Other researchers also reported improved behavioural or biochemical functioning with schizophrenic participants given large doses of vitamin B6. These studies, along with individual anecdotal observations of parents and professionals, led Rimland and colleagues to assess the effectiveness of this orthomolecular treatment. Rimland had recognised that large doses of vitamin B6 produced several undesirable side effects (including irritability, hypersensitivity to sound and enuresis [involuntary urination], which could be countered with doses of magnesium [Mg]). Over the next 19 years, a number of investigators published studies in which attempts had been made to assess the effects of vitamin B6-Mg on a variety of characteristics such as verbal communication, non-verbal communication, interpersonal skills, and physiological function, in individuals with autism.”

 

Current Research

Description of Studies

We have identified 13 articles published in English-language, peer-reviewed journals which evaluate the efficacy of vitamin B6 and magnesium as an intervention for children and young people on the autism spectrum.  Only one of these studies (Kuriyama et al, 2002) evaluated vitamin B6 by itself (without magnesium).

The article by Lelord et al from 1982 appears to describe the same study as the article by Lelord et al from 1981. It is not always clear if any of the other articles by the same research group (which included Barthélémy and Martineau) described unique studies or were articles which described the same studies. 

The studies we identified included more than 300 individuals on the autism spectrum aged from one year old to 18 years old, although the bulk of studies were of children and young people.  Individuals with specific diagnoses included people with autistic disorder, Asperger syndrome or pervasive developmental disorder - not otherwise specified. 

The length of intervention varied between two weeks and 40 months, although in most cases the intervention lasted for between two and 10 weeks.  It is difficult to identify the dosages used because different researchers used different ways of calculating the dosages. For example, Lelord et al (1981) stated that the dosages varied between 400-1125 mg of vitamin B6 and 400-500 mg of magnesium, whereas Tolbert et al (1993) stated that the dosages were 200 mg of vitamin B6 per 70 kg body weight of each participant and 100 mg of magnesium per 70 kg of body weight of each participant.  

Please note: These dosages were well above the recommendations made by The Committee on Toxicity of Chemicals in Food, Consumer Products and the Environment in 2003. The Committee suggested the following dosages: 1.4 mg per day and 1.2 mg per day for males and females respectively.

11 of the studies used a group design, usually comparing a group of people receiving vitamin B6 and/or magnesium to a different group receiving something else. In some of those cases, the other group received a placebo, and, in some cases, the other group received only vitamin B6 or only magnesium.  Two of the studies used single case designs, where the participants received vitamin B6 and magnesium but nothing else.

*Please note: We have not included articles with less than three participants on the autism spectrum, articles which did not examine the efficacy of vitamin B6 and magnesium as an intervention for people on the autism spectrum or articles which examined the efficacy of supplements containing a range of vitamins and minerals.

Outcomes of Studies

Most of the studies (such as Menage et al, 1992; Mousain-Bosc et al, 2006; Rimland et al 1978) reported that vitamin B6 combined with magnesium produced positive benefits on behaviour. For example, Menage et al, 1992 reported “Particularly, improvement was observed for certain autistic symptoms (lack of interest in people, abnormal eye contact, impairment in verbal and non-verbal communication).”

Two of these studies (Barthélémy et al, 1981 and Martineau et al, 1985) reported that vitamin B6 produced no effects by itself and that magnesium produced no effects by itself. However, when combined, vitamin B6 and magnesium produced a range of benefits. For example, Barthélémy et al, 1981 reported improvements in social interaction and social communication, as well as improvements in reactions to the environment.

Only one study (Kuriyama, et al, 2002) reported that vitamin B6 by itself (without magnesium) produced any kind of benefit (significant increase in verbal IQ scores).

Two of the studies (Findling et al, 1997; Tolbert et al, 1993) reported that vitamin B6 and magnesium produced no benefits on behaviour of any kind.

Status Research

There are limitations with most of the research studies into the use of vitamin B6 and magnesium supplements for individuals on the autism spectrum that we have identified to date.
Pfeiffer, S.L. et al. carried out a review of the existing research studies into vitamin B6 and magnesium in 1995. They reported that

“The majority of studies report a favorable response to vitamin treatment. However, interpretation of these positive findings needs to be tempered because of methodological shortcomings inherent in many of the studies. For example, a number of studies employed imprecise outcome measures, were based on small samples and possible repeat use of the same subjects in more than one study, did not adjust for regression effects in measuring improvement, and omitted collecting long-term follow-up data.”

Nye and Brice also carried out a review of the existing research studies into the same intervention for the Cochrane Library in 2005. They reported that

“Only three studies met the inclusion criteria of this review and of these only one study reported adequate data for analysis. Results were inconclusive and sample sizes were small. Therefore, the use of vitamin B6 for improving the behaviour of individuals with autism cannot currently be supported.”

Murza et al also carried out a review of the existing research studies into the same intervention in 2010. They concluded that

“Taken as a whole, the research reported since 2005 support the original conclusions of Nye and Brice, ‘Due to the small number of studies, the methodological quality of studies, and small sample sizes, no recommendation can be advanced based on this review regarding the use of B6-Mg as a treatment for autism. There is simply not sufficient evidence to demonstrate treatment efficacy’.”

For a comprehensive list of potential flaws in research studies, please see ‘Why some autism research studies are flawed’

 

Ongoing Research

We have been unable to identify any studies into vitamin B6 and magnesium that are currently underway or which have yet to report their results. If you know of any studies we should include please email info@researchautism.net with the details.

Future Research

Summary of Existing Research

There is some limited evidence to suggest that certain individuals on the autism spectrum may have a deficiency of vitamin B6. However, the number of individuals on the autism spectrum who have a vitamin B6 deficiency is not clear. It is also unknown whether a vitamin B6 deficiency can cause or worsen symptoms (of autism or related issues) or arises because of autism or is completely unrelated to autism. 

There is a reasonable amount of low-quality research (11 group studies and two single-case design studies with three or more participants) into the use of vitamin B6 and magnesium supplements as an intervention for individuals on the autism spectrum.

However, because the quality of that research is so poor, we cannot determine whether vitamin B6 and magnesium are likely to provide any benefits to anyone on the autism spectrum. We must wait for further research of sufficiently high quality to be completed.

Recommendations for Future Research

There is a need for further research into the use of vitamin B6 and magnesium supplements for people on the autism spectrum.  Specifically, there is a need for studies which use robust methodology, for example, large-scale, placebo-controlled, randomised, double-blind trials carried out on several sites. 

That research should also identify which individuals are most likely to benefit from which formulations and dosages; should determine if vitamin B6 and magnesium supplements can be used as one of the elements within comprehensive, multi-component, treatment models; should compare vitamin B6 and magnesium supplements with other interventions which are designed to achieve similar results, such as special diets.

That research should also identify if vitamin B6 and magnesium supplements have any beneficial or harmful effects in the medium to long term. It should also involve people on the autism spectrum in the design, development and evaluation of those studies.

Studies and Trials

This section provides details of scientific studies into the effectiveness of this intervention for people with autism which have been published in English-language, peer-reviewed journals. If you know of any other studies we should include please email info@researchautism.net with the details. Thank you.

If you are a UK resident you may be able to obtain full copies of some of the items listed here from your local public library, your college library, or the National Autistic Society's Information. Centre. You may also be able to obtain copies from the publisher of the items.

Related Studies and Trials


Other Reading

This section provides details of other publications on this topic. If you know of any other publications we should include please email info@researchautism.net with the details. Thank you.

Please note that we are unable to supply publications unless we are listed as the publisher. However, if you are a UK resident you may be able to obtain them from your local public library, your college library or direct from the publisher.

Related Other Reading


Additional Information

According to Marí-Bauset et al (2015), 

 “Regarding nutrition, this review suggests that dietary assessment often fails to show significant differences compared to DRIs or controls that would indicate compromised nutritional status among children with ASD. Indeed, nutritional requirements in these children in terms of energy and macronutrients seem to be satisfied despite high rates of food selectivity and dietary restrictions. However, the review also found that a wide range of nutritional inadequacies – both excessive and insufficient intake – have been observed in children with ASD. Accordingly, diets need to be assessed on an individual basis accompanied by laboratory data and anthropometric measures, and children should be referred to dietitians as necessary.”

Related Additional Information


Updated
21 Dec 2018
Last Review
01 Dec 2018
Next Review
01 Dec 2021