New research describes neurotoxicity of propionates linked to autism and dementia. 

Propionates occur naturally in the human body, so in the 1980s food authorities considered them safe and they were approved for use as a preservative.

However, since then, research shows propionate-related neurotoxicity. In the US, brain researchers (1) now say:

“Excess levels of propionate appear to be problematic”

According to these researchers, excess levels of propionates can occur due to:

•    a metabolic disorder called propionic acidemia
•    propionate preservatives in diet
•    medications that metabolise to propionic acid

Propionic acidemia

Excess propionate levels that occur in this disorder have been linked to

- developmental delay
- motor and cognitive impairments:
- social impairments
- language delay
- dementia
- epileptic seizures
- autistic symptoms

Propionate preservatives

Since approval as a food preservative, studies have linked these chemicals to:

- behaviour and attention problems in children (2) - yes, that was my bread study published in 2002 - nearly 20 years ago - based on the Lancet report of behavioural effects on children of propionic acid by Swain et al (3) at Royal Prince Alfred Hospital in Sydney. It has never been refuted by further studies.

- autistic type changes in the brains of both rats (4,5) and humans (6)

• • propionate-treated rats are now used as an animal model of autism in research
    
      (See changes in behaviour of laboratory rats given the common bread preservative propionic acid, from The Autism Enigma)
    
    
  • scientists have even suggested that eating this additive during pregnancy may be linked to autism (6)

- diabetes and obesity – a 2019 Harvard study (7) on humans and mice found that

• • a meal containing a low dose of propionate led to a significant increase in plasma levels of propionate in healthy humans
  • exposure to propionate preservatives resulted in insulin resistance in humans and chronic exposure in mice resulted in insulin resistance and weight gain, with propionate appearing to act as a “metabolic disruptor” that could be contributing to the dramatic increases in diabetes and obesity

 - dementia - emerging evidence from researchers at the Department of Neurosurgery and Brain Repair, Morsani College of Medicine, University of South Florida (1) suggests that

• • "excess propionate may play a role in dementia, particularly in Alzheimer’s disease”

Medications that metabolise to propionic acid

• • (1) also suggests that medications such as valproate - with metabolites that include propionic acid - have been linked to reversible dementia, motor and cognitive impairments, Parkinsonism and what looks like brain atrophy but is reversible when the medication ceases.

What our readers say

These are just a few reader reports about preservative 282, see many more in our propionate collection

Reports include behaviour such as irritability, anger, inattention, foggy brain * headaches, migraines *itchy rashes, acne *diarrhoea, stomach cramps, nausea, flatulence * urinary urgency,  incontinence, bedwetting * sleep disturbance including difficulty falling asleep, frequent night waking, night terrors, insomnia *sleep apnoea, snoring, runny nose *addiction, craving propionates * lack of emotional/ social connection *voice problems, speech delay *fatigue, lack of energy * muscle spasms * nosebleeds  *seizures *trichotillomania (hair pulling) *asthma

Autistic symptoms
“I have taken my 3yo son off all commercial bread products …with marvellous results. He was going to be assessed for autistic disorders in a few weeks, but since taking him off 282 he has changed (he talks now! and his behaviour is so much better)”- from story [357]

Chronic fatigue
“I am a busy executive. I love my job but for the last two years I have been feeling tired all the time and struggling to keep up. I was diagnosed with chronic fatigue…I decided to try preservative free bread and GUESS WHAT? I don't have chronic fatigue after all - it was all due to that stupid preservative. People need to know it doesn't only affect kids. When I eat it, I feel tired and need to sleep a lot” – from story [1164]

Seizures
“I have a 2 year old son …l Since changing his diet to preservative free bread , he has gone from a monster to a reasonably placid child, he sleeps well, and his seizures have improved remarkably..”. –from story [1154]

ADHD
"It's been 7 weeks now since we switched to (preservative-free) bread. Within days, my 10 year old ADHD son started improving and we halved his dose of dexamphetamine medication. After four weeks on preservative free bread, he was able to go without medication altogether….The change is huge...” – Anne-Marie from story [224]

Severe speech delay
“a speech therapist at the preschool … diagnosed a severe expressive language delay and a moderate receptive language delay. Six weeks, later when off the bread preservative … she said she had never seen a child change so dramatically within such a short period of time” - from story [036]

Short attention span causing developmental delay
“The introduction of preservative 282 in purchased bread coincided with a decline in our (6yo) daughter’s abilities… she was unable to concentrate for more than about one minute at a time... After two years of under achieving …we returned to using our bread maker… After about ten days…she started concentrating! She finished in 10 minutes what she previously couldn’t finish in 4 hours. Her spelling started to improve as did her handwriting...also learned to ride a bike” – from story [329]

Anger
“I find a huge almost uncontrollable anger building up inside me, for no reason, and I feel I just want to punch something or someone” – 15yo boy describing how preservative 282 makes him feel from story [206]

Social impairment, 282 “addiction”
“My ex-husband had/has Aspergers and when I was able to limit those foods which I knew had negative effect he was a lot more emotionally and socially connected … he would often eat foods he was 'addicted to' (bread with 282 was his major addiction).." – from story [1231]

Moody, stressed out, anxious
“I have always eaten a lot of bread…I used to get very moody, stressed out and anxious... very angry quickly and then in a split second I would feel like crying my eyes out…ongoing rash … very tired and couldn't get up in the morning … decided to stop eating bread (preservative). After three days I felt  better than I have for 6 or 7 years… I used to be a school teacher. If the kids in my class were feeling like I was, I can understand why they behaved the way they did” – from story [207]

Forgetfulness
“My older son …is a very calm and loving child but he used to be so forgetful - like he was in another world. He would get very frustrated at forgetting things and sometimes he would snap. Now (on preservative-free bread) he remembers everything the first time" – Anne-Marie from story [224]

Tired, moody, can’t hold a conversation, terrible handwriting, reverse letters/numbers
“My husband and I …have so much more energy and are less moody on preservative-free bread. With 282, I'm so tired all the time, I can't hold a conversation without losing people, my handwriting is terrible, I write some of my letters backwards, and I've even reversed phone numbers (02 instead of 20). This is really important in my job" – Anne-Marie from story [224]

Migraine
“282 is one of my main triggers for a migraine attack“ – from story [204]

Arrythmia
“when I eat bread preservative, it makes the rhythm of my heart go absolutely crazy. It misses one beat in four and makes me feel quite unwell… wearing a 24 hour heart monitor … 35 minutes after I ate four slices of bread, the graph went wild…” - from story [197]

Urinary incontinence
“We gave up 282 preservatives in bread … within a week my wife (aged 56) was free of urinary incontinence … and over a period of about three months I was able to give up all asthma medications. – readers aged 60 and 56 from story [338]

Sensitive to touch, unable to think clearly
“My 7 year old son…was extremely defiant… talked non-stop, very anxious, had frequent bad dreams and was prone to angry outbursts… I removed the bread preservative 282…He immediately became so much calmer and quieter … less defiant and argumentative, was able to stay still … much more polite and affectionate…It was a lovely change to have him come home from school and give me a spontaneous hug, which is a very rare event as he is so sensitive to touch. He also seems to be able to think more clearly.” – from story [355]

How to avoid propionate preservatives in 3 steps

In Australia, propionate preservatives were first introduced in bread and bakery products such as cakes and pastries but have now expanded to processed meats and more. Worldwide, propionate preservatives are permitted in a wide variety of highly processed foods:

- breads & flour products (tortillas/pizza/pasta/noodles), cakes, pastries, breakfast cereals
- dairy: dried and condensed milk, flavoured milks, dairy-based spreads, cheese
- some processed meats
- some processed fruit and vegetable products
- dairy, egg, and fat-based desserts such as puddings, frosting, confections
- sports drinks, diet foods and beverages
- commercially prepared salads such as potato salad
- condiments such as vinegar and mustard, soups, sauces
- processed mushrooms, beans, seaweeds, nut butters, animal feed and grains
- also occur naturally in Swiss-style cheeses and sourdough breads

1. Propionate preservatives may be listed by chemical name or number …

E280         propionic acid
E281         sodium propionate
E282         calcium propionate
E283         potassium propionate

2. OR they can be hidden under ‘clean label’ ingredient names such as cultured dextrose or fermented wheat flour

AVOID “cultured” or “fermented”  ANYTHING, eg dextrose/whey/wheat flour/rice flour/sugar/whey…
and typically have a label claim: “all natural/no artificial preservatives”

More info in one of our most popular blog posts ever  Beware: cultured dextrose

3. OR you can avoid ALL ultra-processed foods – including commercial breads
 
More info - The Conversation: The rise of ultra-processed foods and why they’re really bad for our health  https://theconversation.com/the-rise-of-ultra-processed-foods-and-why-theyre-really-bad-for-our-health-140537

Macca’s burger buns ditch propionates in the US … but not Australia

In September 2018 McDonald’s in the US announced they were removing artificial preservatives from 7 of their classic burgers including Big Mac. I was pleased to see that the explanation in Forbes magazine included a mention of my bread preservative study published in 2002:

“The buns will no longer have the artificial preservative calcium propionate… McDonald’s may be getting rid of it because previous research found that this preservative could negatively affect children’s behavior. The study, published in the Journal of Pediatrics and Child Health, showed that calcium propionate might cause “irritability, restlessness, inattention and sleep disturbance in some children.” … removing the preservative could reverse these behavioral problems.”

See more in blog

But propionates are natural....

Surely propionates are naturally in the human body and diet isn’t a major source?

Here are the figures:

A person weighing 70kg will produce about 2g propionate per day in their gut by natural processes (8).

The average Westerner eats 2 kg (9) of processed food a day, so he/she will be eating an extra 6g of propionates per day (8) as additives.

Therefore, if you eat processed food, you eat 2-3 times more propionate each day than is produced naturally in your body.

Propionate is a food preservative common in bread but expanding into much processed food (10, 11).

Propionates are increasingly under question for safety as a neurotoxin. There are effects on behaviour, autism and dementia (5,6,7) as detailed above.

“most persons are exposed to dietary sources
of propionate every day” (3).

“further evaluation of the metabolic consequences
of propionate consumption is warranted” (3).

Action required from food regulators

Given dramatic increases in autism diagnoses and dementia and falling school scores since approval of propionate in 1984, at the very least the science and safety of propionate additives require urgent public review in light of this most recent research.

Scientific references

1. Killingsworth J et al, Propionate and Alzheimer's Disease (2021). Front Aging Neurosci, 2021 Jan 11;12:580001. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7831739/

2. Dengate S and Ruben A, Controlled trial of cumulative behavioural effects of a common bread preservative (2002). J Paediatr Child Health, 2002,Aug;38(4):373-6. Irritability, restlessness, inattention and sleep disturbance in some children may be caused by a preservative in healthy foods consumed daily. Minimizing the concentrations added to processed foods would reduce adverse reactions. Testing for behavioural toxicity should be included in food additive safety evaluation https://www.ncbi.nlm.nih.gov/pubmed/12173999 Download this paper (6Mb pdf)

3. Swain A et al, Salicylates, oligoantigenic diets, and behaviour (1985). Lancet,1985 Jul 6;2(8445):41-2.
https://pubmed.ncbi.nlm.nih.gov/2861485/

4. A M Brusque et al, Effect of chemically induced propionic acidemia on neurobehavioral development of rats (1999). Pharmacol Biochem Behav, 1999;64(3):529-34. Propionic academia can be chemically induced by feeding propionic acid to rats and was shown to cause long term developmental delay.  https://pubmed.ncbi.nlm.nih.gov/10548267/

5. MacFabe DF et al. Neurobiological effects of intraventricular propionic acid in rats: possible role of short chain fatty acids on the pathogenesis and characteristics of autism spectrum disorders (2007). Behav Brain Res, 2007,10;176(1):149-69. https://pubmed.ncbi.nlm.nih.gov/16950524/

6. Abdelli A et al, Propionic Acid Induces Gliosis and Neuro-inflammation through Modulation of PTEN/AKT Pathway in Autism Spectrum Disorder (2019). Sci Rep, 2019,19;9(1):8824. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6584527/  Also reported in Medical News Today: Could processed foods explain why autism is on the rise? For the first time, scientists have found a molecular connection between a common food preservative, neuronal disruption, and autism spectrum disorder. The findings suggest that there may be a link between the consumption of processed foods during pregnancy and the rise of autism. https://www.medicalnewstoday.com/articles/325546 

7.Tirosh A et al, The short-chain fatty acid propionate increases glucagon and FABP4 production, impairing insulin action in mice and humans (2019). Sci Transl Med, 2019 Apr 24;11(489):eaav0120. Quote: chronic consumption of propionate leading to an increase in insulin levels might in turn lead to an increase in food intake, weight gain, and insulin resistance https://pubmed.ncbi.nlm.nih.gov/31019023/  Also reported in Harvard Gazette: Could a popular food ingredient raise the risk for diabetes and obesity? Consumption of propionate, an ingredient that’s widely used in baked goods, animal feeds, and artificial flavorings, appears to increase levels of several hormones that are associated with risk of obesity and diabetes, according to new research led by the Harvard T.H. Chan School of Public Health in collaboration with researchers from Brigham and Women’s Hospital and Sheba Medical Center in Israel https://www.shebaonline.org/department/institute-of-endocrinology/ . See also https://www.hsph.harvard.edu/news/press-releases/could-a-popular-food-ingredient-raise-the-risk-for-diabetes-and-obesity/

8. Morrison D. J., Preston T. (2016). Formation of short chain fatty acids by the gut microbiota and their impact on human metabolism. Gut Microbes 7, 189–200. 10.1080/19490976.2015.1134082. https://pubmed.ncbi.nlm.nih.gov/26963409/  It is estimated that in a human being who weighs 85 kg, the gut microbiota produce approximately 29.5 mg/kg of propionate each day via fermentation. Therefore about 2.5g are produced in a body of this size.

9. Center for Disease Control (2006). Low-Energy-Dense Foods and Weight Management: Cutting Calories While Controlling Hunger http://www.cdc.gov/nccdphp/dnpa/nutrition/pdf/r2p_energy_density.pdf  “Research shows that people eat a fairly consistent amount of food on a day-to-day basis. This finding holds true whether the amount of food contains many or few calories.” The average person eats between three and five pounds of food per day.

10. Martínez Steele E, Baraldi LG, Louzada MLDC, et al (2016). Ultra-processed foods and added sugars in the US diet: evidence from a nationally representative cross-sectional study. BMJ Open 2016;6:e009892. https://bmjopen.bmj.com/content/6/3/e009892.full 

11. Morris A. (2019). Metabolic safety of common preservative under scrutiny. Nat Rev Endocrinol. 2019 Jul;15(7):378. https://www.nature.com/articles/s41574-019-0217-3

More info

Introduction to food intolerance

BLOG Caution cultured dextrose

Propionate factsheet

28 page propionate story collection