One patient arrives with an autism diagnosis, another with ADHD, a third with anxiety. On paper, three separate conditions. But order the right labs and the same patterns turn up: low zinc, elevated copper, sluggish methylation, signs of oxidative stress. Outwardly, the diagnoses differ. The underlying biochemistry often doesn’t.
These three diagnoses that present quite differently may, in fact, reflect the same handful of metabolic imbalances.
The overlaps are becoming harder to ignore. A body of research across these conditions points to a shared set of metabolic disturbances that show up in different combinations, and to different degrees, in each person. For a growing number of clinicians, this finding shifts the question from “Which diagnosis is this?” to “Which imbalances is this person actually carrying?”
As more practitioners look past simplistic diagnostic labels like “autism” or “anxiety disorder,” and begin to assess the biochemistry underneath the labels, laboratory testing is becoming less of an afterthought and more of a starting point.
That shift in perspective matters, because these are all heterogeneous conditions, with no single “cause” and no single presentation. Two people with different diagnoses may in fact show very similar metabolic patterns. And it is also true that two patients who’ve been given the same diagnosis can have very different biochemistry driving their symptoms.
Treating diagnostic labels alone misses that. Measuring the biochemistry gives us, as practitioners, some much more specific and objective factors to act upon.
Four Common Processes
Four interrelated processes surface again and again across patients with autism, ADHD, and anxiety.
Oxidative stress is among the most consistent. Children with autism show a lower ratio of reduced to oxidized glutathione—the body’s master antioxidant—than their peers (James, Am J Clin Nutr, 2004). A meta-analysis of six studies found the same association in ADHD (Joseph, J Atten Disord, 2015), and oxidative stress is implicated across anxiety, depression, and other mental health conditions (Salim, Curr Neuropharmacol, 2014).
Decreased methylation is the second. The one-carbon biochemical machinery of methylation helps build and regulate dopamine, serotonin, and norepinephrine—the neurotransmitters tied to attention, mood, and stress. A study in children with autism found that reduced methylation capacity (James, Am J Med Genet B, 2006), and concurrent shortfalls in B6, B9, and B12 can disrupt the whole pathway for production of these key neurotransmitters (Belardo, J Nutr Biochem, 2019).
Mitochondrial dysfunction is the third. The brain is a metabolically expensive organ, so when energy production falters, mood and cognition are altered. Mitochondrial dysfunction is common in autism, with estimates ranging from roughly 30–50% up to 80% in one study (Giulivi, JAMA, 2010).
Poor nutrient status is the fourth. Deficiencies of a host of important nutrients are common in patients with ADHD, autism, and anxiety. This is the most actionable of the four key factors, because the deficiencies are measurable and modifiable.
The Zinc, Copper, and Pyrrole Connection
Nowhere are these connections more clear than in the relationship between zinc, copper, and a marker called kryptopyrrole.
Zinc and copper compete for absorption, so low zinc tends to drive up copper levels. That matters neurologically: zinc helps balance the excitatory and inhibitory signaling processes that are already disrupted in ADHD, autism, and anxiety. Excess copper can push norepinephrine higher, feeding anxiety and hyperactivity. A decreased zinc-to-copper ratio has been tied to severity of autism (Li, Neuroreport, 2014).
Pyrrole disorder (also known as kryptopyrrole disorder or pyroluria) compounds the problem. Elevated kryptopyrrole, indicated by high hydroxyhemepyryrrolin (HPL) in urine, binds and depletes both zinc and B6 before the body can use them, pulling two of the most important cofactors out of circulation at once (McGinnis, Altern Ther Health Med, 2008).
Zinc and copper compete for absorption, so low zinc tends to drive up copper levels. That matters neurologically: zinc helps balance the excitatory and inhibitory signaling processes that are already disrupted in ADHD, autism, and anxiety.
As a result, individuals with elevated kryptopyrroles may develop functional deficiencies despite apparently adequate intake of zinc and B6. In these cases, it’s a functional rather than an intake deficiency, but it can affect neurotransmitter synthesis, antioxidant defenses, immune function, stress resilience, and metallothionein activity, contributing to oxidative stress, copper excess, and neurotransmitter imbalance.
The exact cause of elevated kryptopyrroles is not fully understood, but research and clinical observations suggest links to oxidative stress, genetic susceptibility, chronic inflammation, and disruptions in heme metabolism.
Clinically, pyrrole disorder is associated with anxiety, mood instability, sensory sensitivities, attention difficulties, poor stress tolerance, and other neurobehavioral symptoms.
From Diagnosis to Measurement
The move toward personalized nutrition obliges us to move away from applying generic label-based protocols and toward the use of objective lab markers to tailor our clinical recommendations.
The tools are accessible. We can measure glutathione ratios to gauge oxidative stress. We can look at whole blood histamine and SAM/SAH [S-adenosylmethionine (SAM) / S-adenosylhomocysteine (SAH)] ratios to assess methylation. We can use plasma zinc, serum copper, and the zinc-copper ratio to map mineral balances. A urinary kryptopyrrole test flags pyrrole disorder. Together, these tests turn a vague diagnostic label into a specific, addressable profile.
Elevated kryptopyrrole, indicated by high hydroxyhemepyryrrolin (HPL) in urine, binds and depletes both zinc and B6 before the body can use them, pulling two of the most important cofactors out of circulation at once.
The payoff shows up in the interventions. For example, supplementation with methylcobalamin and folinic acid can improve glutathione status and behavior in children with autism. The greater redox improvement tracks with gains in communication and social skills (Frye, Autism Res Treat, 2013). In adults, higher intake of methyl-donor nutrients was associated with lower odds of anxiety and depression (Lotfi, Br J Nutr, 2022).
Testing & Targeted Support
Judicious lab testing can help guide decisions about nutritional support. For example, markers related to methylation may indicate a need for folate, vitamin B12, or vitamin B6. Zinc and copper testing can help identify the need for mineral supplementation. Mitochondrial dysfunction, antioxidative capacity, or evidence of increased nutrient needs may suggest other targeted nutrition interventions. The specific nutrients, forms, and dosages are personalized based on lab results, symptoms, and biochemical patterns.
Dietary changes can likewise be tailored to address underlying factors such as food sensitivities, inflammation, blood sugar dysregulation, or digestive dysfunction. Testing can also guide dietary strategies aimed at increasing or decreasing certain nutrients, such as improving folate intake or reducing excess copper.
What the Evidence Does and Doesn’t Say
Research into the biochemical signatures that underlie autism, ADHD, and anxiety is opening real possibilities for better treatment of these conditions. But it does carry some real caveats. Many of the strongest findings come from autism research specifically. The data for anxiety and ADHD data are a bit thinner. So, it’s important that we don’t over-generalize from one clinical condition to the others.
Also, keep in mind that nutrient levels vary, and single markers in isolation can be misleading. Biochemistry is only one set of inputs among the many we need to consider. The case here is not that labs replace clinical judgment. It is that they sharpen it.
The direction is clear. As more practitioners look past simplistic diagnostic labels like “autism” or “anxiety disorder,” and begin to assess the biochemistry underneath the labels, laboratory testing is becoming less of an afterthought and more of a starting point. It’s a way to meet each patient’s neurology where it actually is. For a deeper explanation of these biochemical patterns and their clinical implications, see the Clinical Review of Common Patterns in Autism, ADHD, Anxiety and Related Conditions.
Julie Matthews, MS, is a Certified Nutrition Consultant with a master’s degree in medical nutrition from Arizona State University, and 25 years of clinical practice experience. She is the founder of the Bioindividual Nutrition Institute, and the author of The Personalized Autism Nutrition Plan, and Nourishing Hope for Autism.
