In my clinical practice, I’ve observed a fascinating pattern: patients grappling with high levels of oxalates often exhibit elevated benzoic acid levels, coupled with diminished hippuric acid. This correlation is particularly notable among those suffering from interstitial cystitis, a chronic condition characterized by bladder pain and discomfort. Understanding the interplay of these compounds in our bodies can provide invaluable insights into managing and potentially alleviating the symptoms of this distressing syndrome.

What are oxalates?

To elaborate on this topic, it’s important to understand the role of oxalates in the body. Oxalates are natural compounds found in many foods, including healthful options like spinach, kale, nuts, and chocolate. However, for some individuals, particularly those with certain genetic predispositions or gut bacteria imbalances, these oxalates can accumulate excessively, leading to the formation of painful crystals in various body parts, including the kidneys and bladder​​. This condition, known as hyperoxaluria, can lead to several complications, including kidney stones, bladder pain or interstitial cystitis​​.


Hyperoxaluria is classified into two types: primary and secondary. Primary hyperoxaluria is a rare genetic disorder, while secondary hyperoxaluria is often linked to dietary habits or other health conditions that affect oxalate absorption in the gastrointestinal tract​​​​. Treatment strategies generally aim to reduce oxalate levels in the body and prevent the formation of calcium oxalate crystals​​.

Hyperoxaluria can be genetic such as Type 1 Hyperoxaluria

There is also a more commonly form of Hyperoxaluria called Enteric Hyperoxaluria

And an often overlooked pathway is known as Endogenous production of oxalate.

Test, don’t guess!

In my clinic in our signature Root Cause Investigation program, to delve deeper into the underlying causes of these symptoms, we utilize a comprehensive testing approach known as Nutreval. This advanced test allows us to investigate various metabolic pathways that might be contributing to our patients’ discomfort and ailments. One critical aspect of this evaluation focuses on the potential for hyperoxaluria, a condition marked by an excessive accumulation of oxalate in the body.

The Nutreval test is instrumental in identifying imbalances or deficiencies in the body that may lead to or exacerbate hyperoxaluria. By analyzing a range of metabolic markers, we can assess how the body processes oxalate and other related compounds. This information is crucial for patients, especially those with conditions like interstitial cystitis or bladder pain syndrome, as it helps us understand the biochemical underpinnings of their symptoms.

One of the pathways we explore through Nutreval testing is the oxalate metabolism pathway. This pathway reveals how effectively the body is dealing with oxalates – whether they are being properly excreted or excessively accumulated. For patients with symptoms suggestive of hyperoxaluria, such insights are invaluable. They not only confirm the diagnosis but also guide us in tailoring a more effective and personalized treatment plan.

The Nutreval test includes a direct measurement of oxalate levels, which offers vital clues about either dietary exposure or endogenous production of oxalates in the body. This aspect of the test is particularly revealing, as it helps us understand the source of the oxalate overload, which is a crucial step in developing a targeted treatment plan.

It is important to recognize that urinary oxalate stones, a common manifestation of hyperoxaluria, have varied origins. Approximately 60% of these stones are derived from the endogenous metabolism of specific amino acids – glycine, glycolate, and hydroxyproline. This internal metabolic process underscores the complexity of hyperoxaluria, as it’s not solely influenced by dietary habits but also by how the body processes certain naturally occurring substances.

Sources of oxalates

25% to 30% of urinary oxalate stones are the end product of the metabolism of dietary ascorbate, more commonly known as vitamin C. This highlights the role of certain nutrients in oxalate formation and the need for careful dietary management in individuals prone to hyperoxaluria.

The remaining 10% to 15% of oxalate stones originate from direct dietary oxalate intake. This percentage, though relatively smaller, is significant as it points to the direct impact of diet on the development of oxalate stones. Foods high in oxalate, such as spinach, beets, and certain nuts, can contribute to this fraction of oxalate stone formation.

The comprehensive data provided by the Nutreval test allows us to piece together these different contributing factors. By understanding the proportion of oxalate stones derived from endogenous metabolism versus dietary intake, we can tailor a more effective dietary and lifestyle intervention plan for our patients. This approach not only helps in managing the current symptoms but also plays a crucial role in preventing future occurrences of oxalate-related health issues.

The Nutreval test is a powerful tool in our arsenal, enabling us to dissect and understand the multifaceted nature of hyperoxaluria. With this knowledge, we can empower our patients with personalized strategies to manage their condition effectively, improve their quality of life, and prevent the recurrence of painful bladder symptoms associated with oxalate overload.

Benzoic acid and hippuric acid ratio

In my clinical observations, I’ve identified a recurring pattern among many patients: they often present with high levels of benzoic acid and concurrently low levels of hippuric acid. This pattern is not just a mere coincidence but an indicator of underlying metabolic imbalances that could be contributing to their health issues, including bladder pain and interstitial cystitis.

Benzoic acid is a compound commonly found in various foods and products, and it is also produced endogenously in the body. Normally, benzoic acid is converted into hippuric acid in the liver through a process involving glycine, a simple amino acid. Hippuric acid is then excreted through the kidneys. This conversion is crucial because it transforms benzoic acid, which can be harmful in high concentrations, into a more benign form that the body can easily eliminate.

However, when I observe high benzoic and low hippuric acid levels in patients, it suggests a disruption in this metabolic conversion. There are several potential reasons for this imbalance. It could be due to a deficiency in glycine or other cofactors needed for the conversion process. Alternatively, it might indicate an overload of benzoic acid from dietary sources or environmental exposures, overwhelming the body’s capacity to convert it efficiently.

This pattern is particularly significant in the context of oxalate metabolism. As we know, oxalates can contribute to bladder pain and interstitial cystitis. The metabolic disruption indicated by high benzoic and low hippuric acid levels might also impact the body’s ability to handle oxalates effectively, leading to their accumulation and the associated health issues.

Understanding this pattern is crucial for developing targeted treatment strategies. It may involve dietary adjustments to reduce benzoic acid intake, supplementation to support the conversion process, or other interventions to restore balance in the body’s metabolic pathways. By addressing these imbalances, we can help alleviate the symptoms associated with high oxalate levels and improve overall urinary and bladder health.

Let’s dive a bit more into this:

The journal article “Hippuric acid as a significant regulator of supersaturation in calcium oxalate lithiasis: the physiological evidence” discusses the role of hippuric acid in the context of calcium oxalate (CaOX) stones, commonly known as kidney stones. In simple terms, the study highlights these key points:

  1. Role of Hippuric Acid (HA): Hippuric acid is identified as a highly active solvent for calcium oxalate in physiological solutions. This means that it can effectively dissolve calcium oxalate, which is the primary component of many kidney stones.
  2. Research Methods: The study used two main types of experiments: analyzing hippuric acid levels in urine samples of patients with calcium oxalate stones and observing the dissolution of these stones in artificial urine with varying levels of hippuric acid.
  3. Findings on Hippuric Acid Levels: It was found that people without kidney stones (the control group) had hippuric acid concentrations approximately ten times higher than those with stones. This suggests a correlation where higher levels of hippuric acid in urine might help prevent or reduce the formation of calcium oxalate stones.
  4. Therapeutic Implications: The research indicates the potential of increasing hippuric acid concentration in urine as a strategy for both dissolving existing calcium oxalate stones and as a preventative measure against their formation.

In layman’s terms, the study suggests that hippuric acid in urine might play a crucial role in preventing and treating kidney stones made of calcium oxalate by dissolving them, which could be significant for medical treatments and dietary considerations​​.

Hippuric acid levels can be low in some individuals due to various factors:

  1. Diet: A major source of hippuric acid is the gut flora’s breakdown of polyphenols, compounds found in fruits, vegetables, and whole grains. A diet low in these foods can result in lower hippuric acid levels.
  2. Gut Flora Composition: Variations in gut microbiota, which can be influenced by diet, antibiotics, and overall health, can affect the production of hippuric acid.
  3. Liver or Kidney Function: Impaired liver or kidney function can affect the metabolism and excretion of hippuric acid.
  4. Environmental Exposures: Certain environmental toxins or occupational exposures can affect the body’s ability to produce or process hippuric acid.
  5. Genetic Factors: Genetic differences in metabolism can also influence hippuric acid levels.

Understanding the specific reason for low hippuric acid levels in an individual would typically require a detailed medical evaluation, considering diet, health history, and possibly genetic testing.

Benzoic and hippuric conversion

Benzoic acid is converted to hippuric acid through a detoxification process in the body, involving the Phase 1 detoxification pathway. Here’s a simplified explanation:

  1. Ingestion of Benzoic Acid: Benzoic acid is found in various foods and is also used as a food preservative. Once ingested, it enters the body’s detoxification system.
  2. Phase 1 Detoxification: In the liver, Phase 1 detoxification enzymes, particularly cytochrome P450 enzymes, start processing benzoic acid. This phase involves modifying the benzoic acid to make it more water-soluble, facilitating its further breakdown.
  3. Conversion to Hippuric Acid: The slightly altered benzoic acid then combines with glycine, an amino acid, in a process known as conjugation. This conjugation occurs in the liver and results in the formation of hippuric acid.
  4. Excretion: Hippuric acid, being more water-soluble, is then excreted from the body through the urine.

In essence, this process is the body’s way of detoxifying benzoic acid, transforming it into a compound (hippuric acid) that is easier to eliminate, thus maintaining the body’s chemical balance and preventing potential toxic buildup.

To naturally increase hippuric acid levels, one can:

  1. Consume Foods Rich in Polyphenols: These include fruits like berries, cherries, and grapes; vegetables like onions, lacinato kale, and broccoli; low oxalate nuts like macadamia; seeds; and beverages like tea, coffee, and red wine.
  2. Maintain a Healthy Gut Microbiota: Consuming probiotics (like yogurt and kefir) and prebiotics (such as garlic, onions, and bananas) supports beneficial gut bacteria that play a role in converting dietary components into hippuric acid.
  3. Hydration: Drinking adequate water supports kidney function, which is vital for the excretion of hippuric acid.
  4. Limit Exposure to Environmental Toxins: Reducing exposure to toxins can decrease the body’s detoxification burden, potentially impacting hippuric acid levels.
  5. Regular Exercise: Physical activity can influence metabolism and overall health, potentially affecting hippuric acid production.

The conversion of benzoic acid to hippuric acid primarily occurs in the liver, not in the gut. This process involves a reaction with glycine, an amino acid, resulting in the production of hippuric acid which is then excreted by the kidneys. However, the role of gut microbes in this specific conversion is not prominent.

In the context of gut microbiota, their role is more directly relevant in the metabolism of other substances, such as oxalates. Certain gut bacteria, like Oxalobacter formigenes and various Lactobacillus species, play a crucial role in breaking down oxalates. These bacteria can degrade oxalates and thus potentially reduce the risk of oxalate kidney stone formation and accumulation in other tissues​​.

While the gut microbiome has a vast and complex role in overall health, including the metabolism of various compounds, its direct involvement in the conversion of benzoic to hippuric acid is not a primary function. The focus, particularly in the context of conditions like hyperoxaluria and interstitial cystitis, is often on managing oxalate levels, for which the gut microbiome can be quite influential.

Glycine conjugation

Glycine plays a crucial role in converting benzoic acid to hippuric acid through a process known as glycine conjugation. This process occurs primarily in the liver. Here’s how it works:

  1. Conjugation with Glycine: After benzoic acid undergoes initial processing in the liver (Phase 1 detoxification), it reacts with glycine, an amino acid.
  2. Formation of Hippuric Acid: This reaction results in the formation of hippuric acid. Glycine effectively neutralizes benzoic acid, making it less harmful and more water-soluble.
  3. Excretion: The resulting hippuric acid is then easily excreted by the kidneys through urine.

In summary, glycine contributes to detoxification by transforming benzoic acid into a less toxic and more excretable form, hippuric acid.

To increase glycine levels and its bioavailability in your body, there are several strategies you can consider:

  1. Dietary Sources: Incorporate foods rich in glycine into your diet. Good sources include:
  1. Protein-Rich Foods: Especially animal proteins like meat, fish, dairy products, and eggs are high in glycine.
  2. Gelatin and Collagen: These are particularly rich in glycine. Bone broth, made by simmering bones for an extended period, is an excellent source of gelatin. However, too much gelatin can contribute to oxalate for endogenous producers, so care should be taken.
  3. Legumes and Seeds: Certain plant-based foods, like soy products, pumpkin seeds, also contain glycine, albeit in lower amounts compared to animal sources.
  1. Glycine Supplements: Glycine is available as a dietary supplement, often in the form of capsules or powders. Supplementing with glycine can be an effective way to boost your levels, especially if your dietary intake is insufficient or if you have higher requirements due to health conditions.
  2. Balanced Diet for Absorption: To improve the bioavailability of glycine, maintain a balanced diet that supports overall gut health. Adequate fiber, hydration, and a variety of nutrients can help enhance the absorption of amino acids.
  3. Limit Alcohol and Processed Foods: Alcohol consumption and processed foods can stress the liver and affect the metabolism of amino acids. Reducing their intake can help in better utilization of glycine.
  4. Adequate Sleep: Glycine has been shown to improve sleep quality. Interestingly, good sleep can also support the body’s ability to synthesize and utilize amino acids, creating a beneficial cycle.
  5. Regular Exercise: Exercise can improve overall metabolism, including the synthesis and utilization of amino acids like glycine.

Careful with too much glycine supplementation!

The relationship between glycine and oxalate levels in the body is a nuanced aspect of metabolism. Glycine, an amino acid, can indeed influence oxalate production, but it’s important to understand the context and mechanisms involved.

  1. Role of Glycine in Oxalate Synthesis: Glycine is one of the precursors in the synthesis of oxalate in the human body. During metabolism, glycine can be converted into glyoxylate, which can then be either converted into glycine again or oxidized to oxalate. Therefore, in theory, an excess of glycine could potentially lead to an increase in oxalate production.
  2. Primary Hyperoxaluria: This condition is particularly relevant when discussing the relationship between glycine and oxalate levels. Primary hyperoxaluria is a rare genetic disorder where the liver overproduces oxalate, often due to enzyme deficiencies. In such cases, the metabolic pathway that converts glyoxylate to glycine is impaired, leading to an increase in oxalate production. However, it’s important to note that primary hyperoxaluria is a specific medical condition and not typically a result of dietary glycine intake.
  3. Diet and Oxalate Levels: While dietary factors do influence oxalate levels in the body, the impact of dietary glycine on oxalate production is not as straightforward as it might seem. Most dietary oxalate is actually absorbed directly from oxalate-rich foods, such as spinach, rather than being synthesized from amino acids like glycine.
  4. Balancing Glycine Intake: For most people, the body regulates the conversion processes efficiently, and consuming glycine-rich foods or supplements does not automatically lead to a significant increase in oxalate production. However, in individuals with metabolic disorders or kidney diseases, it’s crucial to monitor and manage glycine intake more closely under medical supervision.
  5. Need for Personalized Nutrition: Considering the complexity of these metabolic pathways, dietary recommendations, particularly concerning amino acid intake, should be personalized. People with a history of kidney stones, renal issues, or metabolic disorders may require tailored dietary plans to manage their oxalate levels effectively.

Note- while there is a biochemical pathway connecting glycine to oxalate production, the impact of dietary glycine on oxalate levels is usually modest in healthy individuals. However, in certain medical conditions, such as primary hyperoxaluria, the relationship becomes more significant and requires careful management. As always, dietary changes and supplement use should be approached with the guidance of healthcare professionals, especially for those with underlying health conditions.

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