What is autism?

Autism spectrum disorder (ASD) was first described in the 1940’s by both Leo Kanner and Hans Asperger (1).

The biology of autism is not understood well enough yet to be used as diagnostic criteria, so diagnoses are made based on behavior.

What are some symptoms of autism?

The official diagnostic criteria for ASD (according to the DSM-V) include (2):

1. Persistent deficits in social communication and interaction in multiple contexts.

Examples include:

  • Trouble holding back and forth conversation.
  • Difficulty initiating social interactions.
  • Little sharing of interests or emotions.
  • Deficits in nonverbal communication such as eye contact, facial expressions, and body language.
  • Difficulty starting or maintaining relationships.
  • Inability to share in imaginative play, trouble making friends, or disinterest in peers.

2. Restricted and repetitive behavior patterns, interests, or activities, indicated by at least 2 of the following (currently or in the past):

  • Repetitive body movements, speech, or use of objects (like lining objects up).
  • Strong desire for sameness and routines, resistance to change.
  • Fixated intense interest in unique objects or hobbies.
  • Overly or underly sensitive to sensory stimuli (like indifference to pain or extreme temperatures, dislike of certain sounds or textures, fascination with certain sounds, lights, smells, etc.)

3. Symptoms must appear early in the developmental process but may not become apparent until social demands exceed the capacity to manage them. They could also be masked by learned coping behaviors.

4. Symptoms must negatively impact social functioning, the ability to hold a job, or other significant facets of life. 

5. The symptoms must not be better explained by an intellectual developmental disorder or global developmental delay. If intellectual developmental disorder AND comorbid autism are suspected, social communication should be below what is expected with just the developmental disorder.

Once the diagnosis is made, a severity level is also specified (1 = requiring support, 2 = requiring substantial support, and 3 = requiring very substantial support).

There are also specifiers to indicate whether or not there are also intellectual or language impairments, known medical, genetic, or environmental factors, other neurodevelopmental, mental, or behavioral disorders, or catatonia.

What is the prevalence of autism?

The prevalence ranges around the world, from a low of 1.4 cases per 10,000 children in the Arabian peninsula to 185 cases per 10,000 children in Asia, with an average of 35 cases per 10,000 (3).

According to a 2014 survey, an average of 168 in 10,000 children (1 in 59) have official ASD diagnoses in the United States (4).

Autism is approximately 4 times more common in males than females (4).

Over the last 40 years, there has been a significant increase in prevalence, but it is unclear whether this is due to an actual increase in cases or better diagnostic methods and increased awareness.

What are some hypotheses on the etiology of autism?

The specific biological underpinnings of autism are still being researched. It is likely that there are many sub-types of autism with different causes and contributing factors, manifesting with similar behavioral symptoms.

There is no clear cause or treatment for the disorder, but there are many proposed contributing factors, including but not limited to the following:

1. Immune dysregulation and inflammation

A large body of research has shown that children with autism tend to have higher levels of circulating pro-inflammatory cytokines (5).

They also tend to have more lymphocytes in the lining of their guts, suggesting immune system hyperactivity, possibly triggered by food hypersensitivities (67).

Interestingly, there is new evidence that autoantibodies against the brain may be present in children with autism and their mothers (8).

Some researchers propose a sub-type of autism mediated by immune system hyperactivity and inflammation (910).

2. Oxidative stress

Studies have found that children with autism tend to have lower levels of antioxidants and higher levels of oxidative stress (111213).

3. Poor methylation

There is some evidence that children with autism are more likely to be poor methylators (1112).

4. Genetics

Mothers with the genetic snps MTHFR 677 TT and CBS rs234715 GT+TT have a statistically greater risk of having a child with autism, especially if they do not take prenatal vitamins early on in pregnancy (14).

Monozygotic (identical) twins have a 60% chance of having autism if the other twin has it (compared to no increased risk for fraternal twins) (15).

5. Maternal nutrition

Some studies have found that mothers of children with ASD are less likely to have taken a prenatal supplement or supplemental folate 1-3 months before pregnancy or during the first 2 months of pregnancy (but remember, that is just correlation, and not necessarily causative) (1416).

However, not all studies have found a correlation between prenatal folate or multivitamin use and autism risk (17).

Interestingly, there also appears to be an association between excess vitamin B12 and folate during pregnancy and autism, so the relationship between nutrient status and autism may be U-shaped (18).

Maternal vitamin D status also appears to be associated with autism risk (low vitamin D during pregnancy associated with 2x greater risk) (19).

6. Nutrient deficiencies

Certain types of nutrient deficiencies may increase the risk of autism or other neurodevelopmental delays in children and exacerbate symptoms (20).

1. B-vitamins

One study evaluating B12 levels in the brains of children with ASD (post mortem) showed 3x lower levels of methylcobalamin and adenosylcobalamin compared to those found in the brains of children without autism (21).

2. Vitamin D

Serum vitamin D levels tend to be slightly lower in children with autism (22232425).

3. Vitamin A

Children with autism may be more likely to have vitamin A deficiencies (26).

7. Gut dysbiosis and/or a dysfunctional gut-brain axis

There is an increased incidence of gastrointestinal disturbances in children with autism (constipation, diarrhea, IBS), suggesting an imbalance in the gut-brain axis (27).

Some studies have found that children with autism produce lower than normal levels of digestive enzymes, including lactase (2829).

In addition, individuals with autism tend to have lower levels of Bifidobacterium, Blautia, Dialister, Prevotella, Veillonella, and Turicibacter in their guts, and higher levels of Lactobacillus, Bacteroides, Desulfovibrio, and Clostridium, compared to healthy controls (30).

They also tend to have lower amounts of butyrate and acetic-acid producing bacteria (Ruminococcaceae, Eubacterium, Lachnospiraceae, and Erysipelotrichaceae) and higher amounts of valeric-acid producing bacteria (Acidobacteria) (31).

Gut health plays a role in mental health since the byproducts of gut bacteria (like LPS and butyrate) can affect gene transcription and alter the proportion of pro and anti-inflammatory cytokines produced, while the gut bacteria themselves can impact serotonin production (3233).

On the flip side, mental health can also affect gut health via the HPA axis, the enteric nervous system, and the neuroendocrine system, so the relationship is probably bi-directional (34).

8. Opioid excess hypothesis

Some researchers hypothesize that the incomplete metabolism of gluten and casein leads to increased production of opioid-like peptides that can cross the blood-brain barrier and interact with opioid receptors, which may contribute to autism symptoms (35).

Increased gut permeability (which often occurs in autism) may lead to even more absorption of these incomplete peptides, worsening the effects (36).

9. Mitochondrial dysfunction

People with autism have higher rates of mitochondrial disorders (5% prevalence vs 0.01% in the general population), but it is unclear if this is a cause or consequence of the disorder (37).

10. Environmental agents

There are associations with a wide variety of environmental toxins and increased risk of autism, including:

  • Air pollution (38)
  • Mycotoxins (39)
  • Pesticide exposure (40)

There are many different perinatal and neonatal factors that have been linked to increased risk of autism as well, including (41):

  • Abnormal presentation
  • ABO or Rh incompatibility
  • Birth injury or trauma
  • Congenital malformation
  • Feeding difficulties
  • Fetal distress
  • Hyperbilirubinemia
  • Low 5-minute Apgar score
  • Low birth weight
  • Maternal hemorrhage
  • Meconium aspiration
  • Neonatal anemia
  • Small for gestational age
  • Summer birth
  • Umbilical cord complications

11. Parental age

Older parental age (over 35 or 40) is linked to higher rates of autism, especially in the 1st-born children (42).

What are some diet and lifestyle interventions that may improve functioning?

1. Gluten-free casein-free diet.

The gluten-free casein-free (GFCF) diet is a popular intervention for autism (43).

Some evidence suggests that the GFCF may helpful in at least a subset of children with autism, although we do not yet have the capabilities to determine which children might benefit beforehand (44).

Since dietary intervention is relatively low-risk and may be beneficial, many parents and clinicians try implementing the GFCF diet to see if it might help, even though the research on it has been mixed.

It is important to ensure nutritional adequacy while on a restricted diet, although several studies have found that children on a GFCF diet actually consume more fiber, legumes, and vegetables than children on the standard American diet (4546).

2. Supplementation to support methylation and reduce oxidative stress.

Several studies have shown a benefit from supplementing with 75 mcg/kg of methylcobalamin 2x per week (or injecting every 3 days) and taking 400 mcg folinic acid 2x per day for 2 to 3 months. Markers of methylation and antioxidant status and behavioral scores improved (4748).

However, at least one study on subcutaneous methylB12 injections in children with autism found no significant effects on behavior or antioxidant status (49).

Supplementing with high-dose antioxidants, like vitamin C (8 grams per 70 kg bodyweight per day, as ascorbic acid), has been shown to improve autistic behavior as well (50).

3. Multivitamin-mineral supplementation.

Children with autism tend to have lower levels of biotin, glutathione, SAM, uridine, ATP, NADH, NADPH, sulfate and tryptophan, and higher levels of oxidative stress markers and glutamate (51).

Supplementing with a daily multivitamin-mineral supplement for 3 months has been shown to improve vitamin and mineral status, reduce markers of oxidative stress, improve methylation and antioxidant status, and modestly reduce autism symptoms compared to placebo (52).

4. Vitamin D

Since vitamin D levels tend to be lower in children with autism, supplementing with high doses of vitamin D may be beneficial (23).

One case study found significant improvement in autistic symptoms after vitamin D deficiency was corrected with supplementation (53).

For example, providing 300 IU of vitamin D per kg body weight per day (max dose 5000 IU per day) has been shown to improve symptoms in up to 80% of the children with autism studied (5455).

Additionally, mothers supplementing with 5000 IU of vitamin D per day during pregnancy, and then supplementing their children with 150 IU per kg bodyweight of vitamin D during infancy and childhood is associated with a reduced incidence of autism as well (56).

However, not all studies have shown significant effects (57).

5. Omega-3’s

One small study found that supplementing with 722 mg of DHA (with or without 2000 IU of vitamin D3) significantly improved social awareness scores in children with autism, but other markers did not significantly improve (58).

However, a review of 6 previous studies did not show consistent evidence of any positive effect on behavior (59).

6. Prebiotics

There is some evidence that supplementing with prebiotics (Bimmuno galactooligosaccharide) while on a gluten-free casein-free diet can improve symptoms and behaviors and help rebalance gut flora (60).

7. Vitamin A

Supplementing with vitamin A has been shown to improve autistic symptoms in children who were previously deficient (26).

8. Digestive enzymes

One double-blind placebo-controlled trial found that children with autism taking digestive enzymes (papain and pepsin) with each meal had improved symptoms after 3 months (61).

9. L-Carnitine

It appears that a small subset of people with autism (less than 20%) also have L-carnitine metabolism disorders and may benefit from an L-carnitine supplement (62)

10. Ketogenic diet

Some subsets of patients with autism (especially those with mitochondrial disorders or who have trouble with glucose metabolism) may benefit from a ketogenic diet. (For example, PET scans have suggested that some people with autism have poor glucose metabolism in the brain, in which case ketones may help) (6364).

The ketogenic diet may also increase the production of GABA, reducing the effects of excess glutamate that occurs in some people with autism and help improve mitochondrial function (65666768).

One small study found that 60% of children with autism with mild symptoms who followed a ketogenic diet for 6 months experienced improvements in concentration, learning, and social behavior (69).

A more recent study found that the ketogenic diet (as a modified Atkins diet) was more effective at improving symptoms than a GFGC diet for autism (70).

Another recent study found that 10 out of 15 children with autism who adhered to a modified ketogenic diet with supplemental MCT for 3 months showed significant improvements in autistic behaviors 6 months later (71).

These studies are promising, but more research is needed.

11. Oligoantigenic diet

Given the potential involvement of immune hypersensitivity in autism, a customized oligoantigenic diet (like LEAP), may have some benefit, although there have been no peer-reviewed studies on the topic.

12. Recommended feeding practices (72).

For children with autism who desire routine and dislike change, creating a comfortable and quiet eating environment may help them eventually try new foods. Modeling good eating behaviors yourself may help as well.

Try not to reward behavior with food or treats.

Food chaining, introducing foods of similar color, shape, and texture to preferred foods may increase acceptance of new foods. In general, only introduce one new food at a time, rather than an entire meal of new foods.

Try to get in the habit of purchasing a wide variety of brands and packages of foods to reduce the likelihood of getting stuck on one particular item. Encourage talk, exploration, and play around food to increase comfort and familiarity.

13. Refer to a behavioral therapist.

Working with a Board Certified Behavior Analyst (BCBA) can help improve functioning as well.

Are there any special considerations when working with children with autism?

1. Picky eating

Children with autism tend to have greater food selectivity and a consume a smaller variety of foods, increasing the risk of nutrient deficiencies (7374).

This may be due to both increased sensitivity to taste, texture, shape, color, and even packaging of food and a desire for sameness and routine.

2. Sleep disturbances

Children with autism have higher rates of sleep disturbances, including resistance going to bed, insomnia, parasomnia (sleepwalking, nightmares, etc.), disordered breathing during sleep, trouble waking up, or daytime sleepiness (75).

3. Gastrointestinal problems

Children with autism have a higher prevalence of gastrointestinal conditions, which may cause uncomfortable symptoms that worsen behavior (76).