Sulfite/Metabisulfite

Sulfite and metabisulfite are widely utilized as preservatives and antioxidants in foods, beverages, pharmaceuticals, and even some cosmetic products due to their antimicrobial and anti-browning properties. 

Despite their utility, these compounds can be harmful, with animal studies indicating adverse effects on the lungs, skin, stomach, and eyes, and potential fetal toxicity. 

Sulfites are naturally produced in the human body during the metabolism of sulfur-containing amino acids, with sulfite oxidase converting them to sulfate for excretion. A deficiency in this enzyme, often due to genetic mutations, can lead to elevated sulfite levels, causing diseases such as asthma, neurological disorders, and heart disease. 

Sulfite intolerance, particularly prevalent in those with asthma or the "aspirin triad," can exacerbate respiratory conditions and lead to severe reactions. 

Therefore, understanding the metabolism, health impacts, and testing for sulfite sensitivity is crucial for managing exposure and mitigating risks.

What is Sulfite/Metabisulfite?

Sulfite and metabisulfite are widely used as preservatives and antioxidants in foods, beverages, and pharmaceuticals due to their ability to inhibit the growth of microorganisms and prevent oxidation [5., 8.]. They are also found in some cosmetic products including hair straightening or waving products [8.].

Toxicity of Sulfite/Metabisulfite

Animal studies of these compounds have demonstrated adverse pulmonary, dermal, gastric and ocular effects, as well as fetal toxicity [5., 8.].

Their carcinogenicity in humans could not be verified in one toxicity assessment [8.].

Sulfite and Metabisulfite in Human Health

Sulfites are naturally generated in humans as a byproduct of the processing of the sulfur-containing amino acids cysteine, and methionine [5., 8.].

Endogenous sulfite levels are maintained at low concentrations by a mitochondrial enzyme called sulfite oxidase, which converts sulfite to sulfate, which is then subsequently excreted in the urine [5., 8.].

Loss of sulfite oxidase activity, which requires molybdenum for proper functioning, can lead to elevated sulfite levels [4.]. Elevated sulfite levels can contribute to diseases such as asthma, neurological dysfunction, birth defects, and heart disease [5.].

Sulfite's cytotoxicity is linked to the formation of sulfite radicals, primarily generated by heme-peroxidases through a one-electron oxidation pathway, and subsequent depletion of glutathione and other essential antioxidants [3., 5., 9., 13.]. 

The interaction of sulfite with various metalloproteins, essential parts of the human antioxidant  and cellular functioning systems, in vivo is attributed to sulfite’s effects on human health [5.].

Genetic Mutations Affecting Sulfite/Metabisulfite Processing

Genetic deficiencies in sulfite oxidase can result from mutations in the SUOX gene or defects in molybdenum cofactor synthesis, caused by mutations in MOCS1, MOCS2, GPHN, or MOCS3 genes [10., 12.].

These deficiencies lead to severe neurological abnormalities and often early death [2., 10.]. Specific mutations, such as R160Q in the SUOX gene, can significantly reduce enzyme activity by altering substrate binding and catalytic efficiency [2.].

Diagnosis of sulfite oxidase deficiency can be challenging, but early detection is crucial. Key clinical features include early-onset seizures and neurological deterioration, while laboratory tests for homocysteine and uric acid levels can aid in diagnosis [12.].

Adverse Health Effects Associated with Sulfite/Metabisulfite Exposure

Asthma

Metabisulphite-containing foods have been known to provoke mild asthma and asthma exacerbations in sensitive individuals. 

There is strong evidence for sulfites causing asthma and anaphylaxis 11.]. Severe complications, including status asthmaticus, can occur in sulfite-sensitive asthmatics following exposure to metabisulfites in medications or alcoholic beverages [1., 6.]. 

Metabisulfite intolerance is found in 8% of extrinsic asthma cases and 20% of cases involving the "aspirin triad," which includes nasosinusal polyposis, asthma, and aspirin sensitivity [6.].

These cases stimulated the call for a need for better labeling of additives in medications to allow physicians to identify potential adverse reactions [1.].

Neurological Disorders

Sulfite can have significant neurological effects, particularly in individuals with sulfite oxidase (SO) deficiency. 

SO deficiency leads to sulfite accumulation, causing seizures and progressive encephalopathy. Sulfite exposure can impair mitochondrial function, reduce antioxidant capacity, and induce glial reactivity and neuronal damage [3.].

One study involving rats showed that the cerebral cortex and striatum were most susceptible to sulfite toxicity, showing significant oxidative and bioenergetic disruptions. This is likely due to their higher metabolic activity and greater need for robust antioxidant defenses [3.]. 

Cardiovascular Disease

Sulfite and related sulfur-containing molecules play crucial roles in cardiovascular health. 

Sulfite, while potentially toxic, is regulated by sulfite oxidase and can form sulfite radicals implicated in various diseases [5.].

The metabolism of sulfur-containing amino acids is redox-dependent and linked to the one-carbon metabolic cycle, folate cycle, and glutathione maintenance. Dysregulation of these pathways is associated with cardiovascular disorders, often characterized by abnormal plasma levels of sulfur-containing amino acids [7.].

Lab Testing for Sulfite/Metabisulfite

Test Information, Sample Collection and Preparation

Increasingly, laboratory companies are developing new technology to meet the increasing demand for diagnostic testing. This includes assessment for sensitivities to compounds such as sulfite and metabisulfite. Traditionally there has not been a widely accepted allergy test to diagnose sulfite sensitivity. 

Some genetic testing companies offer testing for SNPs, or single nucleotide polymorphisms, which may alter the enzymatic function of enzymes like SUOX and therefore allow the buildup of sulfites. Click here for an example of this type of testing.  

Other companies have developed technology to observe immune reactions of specialized white cells (lymphocytes) just as they occur in your body. By looking directly at lymphocytes, this testing detects all three types of delayed food and chemical hypersensitivities: type 2 (includes IgA, IgM, IgG), type 3 Immune Complex, and type 4 T cell-mediated.

This allows for the assessment of an immune response to many foods and food additives, including sulfites and metabisulfites. Click here to explore this test.

Genetic testing can be done with blood, saliva, or a cheek swab. 

Lymphocyte testing requires a blood sample, obtained through venipuncture. 

Interpretation of Test Results

Interpretation of genetic testing or of lymphocyte testing should be done under the guidance of a licensed healthcare professional. 

Resources for better understanding these test results can be found below.

Class: Genetic Testing: Implementation Through Functional Medicine

Class: Treating Patients at the Genetic Level

Class: Genetics and Epigenetics: Turning Insight Into Action

Test Introduction: Why LRA (Lymphocyte Response Assay)?