Sulfur

Sulfur is a vital element for human health, playing critical roles in protein synthesis, detoxification, and cellular functions. Primarily obtained from dietary sources like sulfur amino acids (methionine and cysteine) and inorganic sulfur compounds, sulfur is metabolized into sulfites and then converted to sulfates for excretion. 

This process involves enzymes like sulfite oxidase, which requires molybdenum to function properly. 

Sulfur amino acids are precursors to essential molecules such as glutathione, a major antioxidant, and taurine, crucial for cardiovascular health. 

Sulfur also contributes to gene expression regulation and the methylation process, impacting DNA and protein functions. 

Adequate intake of sulfur through a balanced diet, including foods like garlic, onions, cruciferous vegetables, and protein sources, is essential. However, excessive sulfur can lead to health issues, including neurological dysfunction and developmental disorders. 

Understanding sulfur's multifaceted roles underscores the importance of balanced nutrition and appropriate dietary intake to maintain optimal health and prevent related diseases.

What is Sulfur?

Sulfur is an essential element in the human body, primarily excreted in urine as sulfate, derived from both dietary inorganic sulfur (IS) and sulfur amino acids [5.].

Inorganic sulfur sources are commonly sulfiting agents, commonly used as food additives and preservatives, although they are also present in some pharmaceuticals and cosmetics [12., 17.].

Sulfites are normally converted to sulfates which are then excreted in the urine [12., 17.].

The sulfur-containing amino acids cysteine and methionine are the primary dietary sources of sulfur, and they are processed to create sulfites, which are then converted to sulfates and these are excreted from the body in urine [12., 17.].

Sulfur is essential for human health. However, excessive sulfur accumulation can lead to an abundance of sulfites, which has negative health consequences, the most serious of which is severe neurological and developmental issues and death [3.].

Sulfur Processing to Sulfite and Sulfate in Humans

Sulfites are naturally generated in humans as a byproduct of the processing of the sulfur-containing amino acids cysteine and methionine [12., 17.].

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 [12., 17.].

Loss of sulfite oxidase activity, which requires molybdenum for proper functioning, can lead to elevated sulfite levels [26.]. Elevated sulfite levels can contribute to diseases such as asthma, neurological dysfunction, birth defects, and heart disease [12.].

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 [10., 12., 24., 27.]. 

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 [12.].

Sulfur in Human Health

Roles of Sulfur in Cellular and Tissue Health

Sulfur, in its metabolized form sulfate, is essential for various cellular processes, including the sulfonation of steroids, proteins, and proteoglycans [6.]. 

Sulfur plays a crucial role in various biochemical processes, including protein synthesis, methylation, and oxidative stress regulation [23.].

Sulfonation, mediated by sulfotransferases, is critical for modifying biological activities of endogenous compounds and maintaining normal tissue structure [6., 7.]

Sulfate transport across cell membranes is facilitated by specific transporters, primarily from the SLC26 gene family [28.].

Sulfur in Fetal Development

Sulfur, in its metabolized form as sulfate, is essential for fetal development, with fetal tissues relying on maternal sulfate supply due to limited production capacity [6.].

Defects in sulfate metabolism can lead to various developmental disorders, particularly affecting bone and cartilage formation [6.].

Joint Health [19.]

Sulfur-containing compounds like chondroitin sulfate and glucosamine sulfate are essential for maintaining healthy joints. These compounds contribute to the formation and repair of cartilage and other connective tissues. 

A deficiency in sulfur can impair the synthesis of glycosaminoglycans (GAGs), such as chondroitin sulfate, which are vital for cartilage integrity and function.

Phase II Liver Detoxification [25.]

Sulfate, which is produced from sulfur, is an essential compound in phase II liver detoxification through the action of sulfotransferases (SULTs). 

These enzymes catalyze the transfer of a sulfonate group to various substrates, including xenobiotics and endobiotics, making them more hydrophilic and easier to eliminate.

Sulfated Steroid Hormones

Sulfated steroid hormones play a crucial role in reproductive processes and endocrine function. Initially considered inactive metabolites, these compounds serve as a storage reservoir for biologically active hormones [15.].

Sulfation enhances circulatory transit of hydrophobic steroids, while desulfation by steroid sulfatase (STS) activates them in target cells [16.].

Sulfated steroids are transported into cells via organic anion-transporting polypeptides [16.]. 

Estrogen sulfurylation in target tissues, such as the uterus and mammary tumors, may control the availability of 17β-estradiol to cytoplasmic receptors [4.].

The German Research Foundation established a research group to investigate the biological significance of sulfated steroid hormones in reproduction, focusing on transport, sulfation, desulfation, and effects on steroid biosynthesis and membrane receptors [9.].

Adverse Health Effects Associated with Inappropriate Sulfur Processing

Issues with the processing of sulfur and inorganic sulfites to sulfate for excretion in the urine are associated with a variety of health problems, the most serious being those associated with homozygous genetic defects in the enzymes responsible for sulfur processing.

Genetic Conditions 

Sulfite Oxidase Deficiency and Molybdenum Cofactor Deficiency are two genetic disorders associated with suboptimal sulfur processing.

Sulfite Oxidase Deficiency (SOD) [3.]

Sulfite Oxidase Deficiency (SOD) is a rare autosomal recessive disorder caused by mutations in the SUOX gene. This condition results in severe neurological dysfunction, ectopia lentis, and increased urinary excretion of sulfite, thiosulfate, and S-sulfocysteine. SOD manifests in two forms: severe early-onset and milder late-onset.

Early-Onset SOD presents within hours to days of life with symptoms such as intractable seizures, feeding difficulties, progressive encephalopathy, abnormal muscle tone, progressive microcephaly, and profound intellectual disability. Lens subluxation or dislocation may also occur. Most affected infants die within the first few months of life.

Late-Onset SOD appears between six and 18 months of age, presenting with developmental delays, movement disorders, ataxia, and occasionally metabolic strokes. The clinical course can be progressive or episodic.

Diagnosis involves detecting elevated urinary thiosulfate and S-sulfocysteine, low urinary organic sulfate, and significantly reduced plasma total homocysteine. Confirmation is through identifying pathogenic variants in the SUOX gene.

There is no cure for SOD. Management focuses on symptomatic treatment, including anti-seizure medications, spasticity reduction, early gastrostomy tube placement, regular chest physiotherapy, and management of gastroesophageal reflux and aspiration pneumonia.

Molybdenum Cofactor Deficiency (MoCD) [1., 11.]

Molybdenum Cofactor Deficiency (MoCD) is a severe autosomal recessive neonatal disorder characterized by intractable seizures, feeding difficulties, severe developmental delay, microcephaly, and coarse facial features. 

MoCD results in the deficiency of molybdenum cofactor-dependent enzymes: sulfite oxidase, xanthine dehydrogenase, aldehyde oxidase, and mitochondrial amidoxime reducing component, leading to the accumulation of neurotoxic substances such as sulfite and S-sulfocysteine.

Infants with MoCD appear normal at birth but develop symptoms within hours to weeks, including seizures, encephalopathy, hyperekplexia, and poor feeding, leading to severe developmental delays. 

These infants typically do not achieve milestones such as sitting or speaking, and microcephaly is common.

Diagnosis of MoCD involves identifying decreased serum and urine uric acid, elevated urinary sulfite, S-sulfocysteine, xanthine, and hypoxanthine. Genetic analysis reveals biallelic pathogenic variants in the MOCS1, MOCS2, or GPHN genes, with MOCS1 mutations responsible for MoCD Type A.

Both conditions highlight the critical importance of early diagnosis and intervention to manage symptoms and improve quality of life.

Asthma

Sulfite-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 [20.]. Severe complications, including status asthmaticus, can occur in sulfite-sensitive asthmatics following exposure to metabisulfites in medications or alcoholic beverages [2., 13.]. 

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 [13.].

These cases stimulated the call for a need for better labeling of additives in medications to allow physicians to identify potential adverse reactions [2.].

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 [10.].

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 [10.]. 

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 [12.].

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 [14.].

Healthy Sulfur-Rich Foods [8.]

In the absence of a sulfur or sulfite sensitivity, the following healthy foods will promote sulfur utilization in the body and support overall health:

Allium Vegetables

• Garlic

• Onions

• Leeks

• Chives

• Shallots

Cruciferous Vegetables

• Broccoli

• Cabbage

• Brussels sprouts

• Cauliflower

• Kale

Protein Sources

• Eggs

• Fish

• Poultry

• Red meat

Legumes and Nuts

• Beans

• Lentils

• Peanuts

• Soybeans

Dairy Products

• Milk

• Yogurt

• Cheese

Fruits

• Strawberries

• Pineapple

• Kiwi fruit

Grains and Seeds

• Whole grains (e.g., oats, wheat)

• Sunflower seeds

Other Vegetables

• Asparagus

• Okra

• Spinach

Seaweed

• Red seaweed (e.g., used in carrageenan production)

Beverages

• Sulfur-rich mineral waters

Highly-Processed Foods High in Sulfites [8.]

The following foods are high in sulfites, and should be avoided by individuals with a sulfur or sulfite sensitivity: 

Alcoholic Beverages

• Wine

• Beer

Dried Fruits

• Raisins

• Apricots

• Prunes

Processed Vegetables

• Dried potatoes

• Pickled vegetables

Processed Seafood

• Shrimp

• Lobster

• Canned clams

Meat Products

• Sausages

• Hot dogs

• Processed deli meats

Baked Goods

• Crackers

• Biscuits

Condiments

• Mustard

• Salad dressings

Canned and Bottled Beverages

• Bottled lemon and lime juice

• Soft drinks

Snack Foods

• Potato chips

• Popcorn

Prepared and Fast Foods

• Sauces and gravies used in fast food

Laboratory Testing for Sulfur 

Test Information, Sample Collection and Preparation

Sulfur levels may be directly tested in urine or hair to assess levels of elemental sulfur in the body. Sulfated compounds including sulfated steroid hormones and other small sulfated molecules may be tested in the blood. Hydrogen sulfide levels may be tested in the breath. 

Urine and hair samples can be collected from the comfort of home. It is important to consult with the ordering provider prior to sample collection, as special preparation may be required. 

Interpretation of Sulfur Test Results

Optimal Levels of Sulfur

Optimal ranges will vary depending on the sample type used. 

One laboratory company reports the following optimal levels of sulfur in hair: 44000- 51000 μg/g [21.]

Another laboratory company reports the following optimal levels of sulfur in urine: 367-1,328 mg/g creatinine [22.]

Clinical Significance of Elevated Sulfur Levels

Elevated sulfur levels may require further assessment of dietary intake as well as sulfur processing disorders.

Clinical Significance of Decreased Sulfur Levels

Low sulfur levels may prompt a dietary assessment and recommendations to increase sulfur-rich foods. 

FAQ: Sulfur

Sulfur is a naturally occurring element that plays a vital role in various biological and industrial processes. This FAQ section addresses common questions about sulfur, its properties, uses, and related health considerations.

What is Sulfur?

Sulfur is a chemical element with the symbol S and atomic number 16. It is a non-metal that is abundant in nature and is found in various minerals, as well as in the form of sulfates, sulfites and sulfides.

What are Sulfur Uses?

Sulfur has a wide range of uses. It is used in the production of sulfuric acid, which is vital for industrial processes. It is also used in the vulcanization of rubber, the manufacture of fertilizers, and as a fungicide and pesticide in agriculture. 

In the pharmaceutical industry, sulfur is used in the production of certain medications and ointments.

Sulfur has important implications in both health and disease. 

What are Sulfur Burps?

Sulfur burps are burps that smell like rotten eggs, which is caused by the presence of hydrogen sulfide gas in the digestive system. 

This can occur due to certain foods, infections, or digestive disorders. Common triggers include high-sulfur foods, carbonated beverages, and bacterial overgrowth in the gut.

What Does Sulfur Smell Like?

Sulfur itself is odorless, but its compounds, such as hydrogen sulfide (H₂S) and sulfur dioxide (SO₂), have distinct smells. Hydrogen sulfide smells like rotten eggs, while sulfur dioxide has a sharp, pungent odor that can be irritating.

Is Sulfur a Metal?

No, sulfur is not a metal. It is a non-metal element that is classified as a chalcogen. Sulfur has several allotropes, with the most stable and common form being a yellow crystalline solid.

What Foods are High in Sulfur?

Foods high in sulfur include garlic, onions, leeks, cruciferous vegetables (such as broccoli, Brussels sprouts, and cabbage), eggs, meat, fish, and legumes. 

These foods contain sulfur-containing compounds that are beneficial for health.

Why is Sulfur Important for the Body?

Sulfur is essential for the production of amino acids (such as cysteine and methionine) and vitamins (such as biotin and thiamine). It plays a crucial role in detoxification processes, collagen synthesis, and maintaining the health of skin, hair, and nails.

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