Glycolic Acid

Glycolic acid, commonly recognized in skincare as an alpha hydroxy acid (AHA) derived from sugarcane, is one of the smallest molecules in the AHA family, enabling it to penetrate the skin more effectively. 

Beyond skincare, glycolic acid is an important organic acid in human metabolism, produced as a byproduct of the oxalate pathway.  It plays a role in various metabolic pathways including ketone body synthesis and degradation, citrate cycle, and amino acid metabolism. 

Elevated levels of glycolic acid in urine can indicate metabolic disorders such as primary hyperoxaluria type 1 (PH1), characterized by a deficiency in the enzyme alanine

aminotransferase (AGT). 

This deficiency leads to the accumulation of glycolic acid, contributing to severe acidosis and organ impairment in cases of ethylene glycol poisoning. 

Understanding glycolic acid's role in these metabolic processes and its implications in health and disease is crucial for both clinical diagnosis and therapeutic interventions.

What is Glycolic Acid?

Glycolic acid is most commonly thought of in the realm of skincare, where it is an alpha hydroxy acid (AHA) derived from sugarcane.  It is one of the smallest molecules in the AHA family, allowing it to penetrate the skin more effectively than other AHAs.

In the body, glycolic acid is an organic acid produced as a byproduct of the oxalate pathway, making it an important marker for certain physiological and pathological processes.  

Glycolic Acid in Human Metabolism

Glycolic acid is involved in multiple metabolic pathways.  

These pathways include the synthesis and degradation of ketone bodies, citrate cycle, alanine, aspartate, and glutamate metabolism, pyrimidine metabolism, butanoate metabolism, pyruvate metabolism, fatty acid biosynthesis, and the degradation of valine, leucine, and isoleucine.  [3.] 

Extremely high levels of urinary glycolic acid are suspicious of an inborn error of metabolism like primary hyperoxaluria type 1 (PH1), caused by a deficiency in the enzyme alanine:glyoxylate aminotransferase (AGT).

Normally, glycolic acid is derived from sources such as glyoxal and glyoxylate metabolism from lipid peroxidation or protein glycation, ethylene glycol processing, and collagen turnover.  [3., 4., 8.] 

In cases of ethylene glycol poisoning, the rapid metabolism of ethylene glycol to glycolate and subsequent conversion to oxalate leads to severe acidosis and organ impairment.  [4.] 

Extremely high plasma and urine concentrations of glycolic acid and lactic acid are noted in such poisoning cases, contributing to severe anion-gap acidosis and multi-organ dysfunction.

A large portion of glycolic acid is derived from the metabolism of glycine and hydroxyproline, with 20-50% estimated to come from collagen turnover in the form of hydroxyproline.  [8.] 

Glycolic acid is identified as a well-established precursor to oxalate.  It contributes to approximately 1.3% of oxalogenesis in healthy individuals and 47.3% in primary hyperoxaluria type 1 (PH1).  [4.] 

Glycolic Acid in Primary Hyperoxaluria Type 1 

Primary hyperoxaluria type 1 (PH1) is caused by a deficiency of the liver-specific enzyme alanine:glyoxylate aminotransferase (AGT). The pathogenesis of PH1 involves the following key mechanisms:

AGT Deficiency

PH1 is an autosomal recessive disorder caused by mutations in the AGXT gene that encodes the AGT enzyme. This deficiency leads to impaired metabolism of glyoxylate, a metabolic precursor of oxalate.

Accumulation of Glyoxylate 

In the absence of functional AGT, glyoxylate cannot be converted to glycine. Instead, glyoxylate accumulates in the liver cytosol.

Conversion to Oxalate 

The accumulated glyoxylate is then oxidized to oxalate by the enzyme lactate dehydrogenase (LDH).

Hyperoxaluria

The excessive production of oxalate leads to increased urinary excretion of oxalate, a condition known as hyperoxaluria.

Calcium Oxalate Crystal Formation 

The high levels of oxalate in the urine combine with calcium to form insoluble calcium oxalate crystals, leading to the formation of kidney stones (nephrolithiasis) and deposition of crystals in the kidneys (nephrocalcinosis).

Kidney Damage and Failure 

The accumulation of calcium oxalate crystals in the kidneys causes progressive kidney damage, which can ultimately lead to end-stage renal disease (ESRD) if left untreated.

Systemic Oxalosis

In advanced stages, the excessive oxalate can deposit in other tissues and organs, such as bones, eyes, heart, and blood vessels, leading to systemic complications.

What Are Organic Acids?  [2., 6.]

Organic acids are organic compounds with acidic properties.  They include a variety of functional groups like carboxyl, phenol, enol, and thiol, with carboxylic acids having the strongest acidity.

Organic acids are considered weak acids, with those containing phenol, enol, alcohol, or thiol groups being even weaker.  

Their structures vary in terms of carbon chain types—aromatic, aliphatic, alicyclic, heterocyclic—saturation, substitutions, and the number of functional groups. 

These acids play critical roles in metabolic and catabolic pathways, notably in the tricarboxylic acid cycle inside mitochondria, which is central to energy production in eukaryotes.  They are also pivotal in determining the sensory properties of fruits and vegetables.

Some organic acids are produced as byproducts of toxin metabolism, and their presence indicates the degree of exposure to parent toxins.  

Organic Acid Disorders  [1., 10.]

Organic acid disorders are inherited metabolic conditions that affect the enzymes or transport proteins essential for the breakdown of amino acids, lipids, or carbohydrates. They are marked by the excessive excretion of non-amino organic acids in urine, primarily due to defects in specific enzymes involved in amino acid breakdown that cause buildup of organic acids in tissues.

Conditions can manifest as inborn metabolic disorders of organic acids and amino acids, urea cycle anomalies, and mitochondrial respiratory chain deficiencies.

These disorders are typically passed down through autosomal recessive inheritance.  They often present in newborns with symptoms like vomiting and lethargy, progressing to more severe neurological symptoms. 

Early diagnosis and intervention are critical and can improve outcomes. Diagnostic methods include urine organic acid analysis via gas chromatography-mass spectrometry (GC/MS). 

Current treatments focus on managing symptoms and preventing complications, although definitive therapies are still under research.  Treatment focuses may include dietary management, detoxifying harmful metabolites, and in severe cases, organ transplantation. 

Continuous monitoring and management are essential for managing symptoms and preventing complications.

Organic Acid Testing in Functional Medicine

Organic Acid Testing in Functional Medicine

In functional medicine, organic acid testing is utilized to evaluate a patient's metabolic function through a simple urine test. This testing can identify metabolic imbalances that may affect a patient’s mood, energy, and overall health. 

Testing provides insights into nutrient deficiencies, dietary habits, toxic exposures, and gut microbiome activity. 

The results assist practitioners in customizing treatment plans to address specific metabolic dysfunctions and improve health outcomes. 

Additionally, it helps in assessing the impact of microbial metabolism and the efficiency of the Krebs Cycle, aiding in personalized healthcare.

Laboratory Testing for Glycolic Acid

Test Information, Sampling Methods and Preparation

Laboratory testing for organic acids including glycolic acid is typically done in urine, although it can also be tested in blood.  Testing may be ordered to diagnose an inborn metabolic disorder, or to assess metabolic function and gastrointestinal health in a functional medicine setting.  

Urine samples may be collected in a clinical setting; they can also be collected at home.  Some labs recommend or require a first morning void sample, to provide a concentrated sample.  

Interpreting Glycolic Acid Results

Optimal Range for Glycolic Acid Testing

Generally, falling within reference ranges for organic acids is recommended, although for many of these organic acids, a level towards the lower end of the reference range is considered optimal.  

It is essential to consult with the laboratory company used for their recommended reference range for glycolic acid.  

One company reports the following optimal range for glycolic acid:  </= 67 mmol/mol creatinine.  [9.]

Clinical Significance of Elevated Levels of Glycolic Acid

Extremely high levels of urinary glycolic acid are suspicious of an inborn error of metabolism like primary hyperoxaluria type 1 (PH1), caused by a deficiency in the enzyme alanine:glyoxylate aminotransferase (AGT).

In PH1, the blocked oxalate pathway leads to increased production of both glycolic acid and oxalic acid, resulting in oxalate deposition and kidney damage.

With a finding of elevated glycolic acid, oxalate levels should also be assessed.  

Aside from inborn errors, higher glycolic acid levels may indicate increased oxidative stress from lipid peroxidation and/or protein glycation, as more glyoxal is converted to glycolic acid when glutathione levels are adequate.

Recent intake of collagen or collagen-rich foods can influence urinary glycolic acid levels due to its derivation from hydroxyproline.

Clinical Significance of Low Levels of Glycolic Acid

Low levels of glycolic acid are not considered clinically relevant.

Frequently Asked Questions (FAQs) on Glycolic Acid

The FAQ section addresses common questions and concerns about glycolic acid, providing clear and concise answers for better understanding.

What Is Glycolic Acid?

Glycolic acid is an alpha-hydroxy acid (AHA) derived from sugarcane. It is known for its small molecular size, which allows it to penetrate the skin effectively, making it a popular ingredient in skincare products for exfoliation and skin rejuvenation.

Glycolic acid is also an organic acid normally produced in the human body and excreted in the urine.  Elevated levels may signal an inborn error of metabolism, or a condition such as increased oxidative stress and/or increased collagen intake or turnover.  

What Does Glycolic Acid Do?

In the skin, glycolic acid exfoliates the skin by breaking down the bonds between dead skin cells, allowing them to be removed more easily.  [7.] 

This process reveals fresher, smoother skin underneath and can help reduce the appearance of fine lines, acne scars, and hyperpigmentation.

How Does Glycolic Acid Work?

Topically, glycolic acid works by loosening the bonds that hold dead skin cells together on the surface of the skin. [7.] 

Its small molecular size enables it to penetrate deeply into the skin, promoting cell turnover and stimulating collagen production, which helps improve skin texture and tone.

Glycolic Acid vs. Salicylic Acid: What’s the Difference?

Glycolic acid is an alpha-hydroxy acid (AHA) that primarily exfoliates the surface of the skin, making it effective for treating fine lines, dullness, and uneven texture.  

Salicylic acid is a beta-hydroxy acid (BHA) that penetrates deeper into the pores, making it ideal for treating acne and oily skin. Both acids have exfoliating properties but target different skin concerns.

What Are the Benefits of Glycolic Acid for Skin?

Glycolic acid offers several benefits for the skin, including exfoliation, improved texture, reduced hyperpigmentation, and enhanced radiance. It can also help minimize the appearance of fine lines and wrinkles and improve the overall tone and clarity of the skin.

How Should I Use Glycolic Acid for Skin Care?

Glycolic acid can be found in various skincare products, including cleansers, toners, serums, and peels. Start with a lower concentration to see how your skin reacts and gradually increase the strength as tolerated. 

It is typically applied in the evening after cleansing and before moisturizing. 

Always use sunscreen during the day when using glycolic acid, as it can increase your skin’s sensitivity to the sun.

Can Glycolic Acid Be Used for Armpits?

Yes, glycolic acid can be used for the armpits to help with exfoliation and improve the appearance of the skin.  It can reduce hyperpigmentation and smooth the texture of the skin. 

Use a product specifically formulated for sensitive areas and follow with a moisturizer to prevent irritation.  Consult a dermatologist prior to use.  

What Are Ordinary Glycolic Acid Products?

The Ordinary is a skincare brand known for its affordable, effective products. 

Their glycolic acid offerings include The Ordinary Glycolic Acid 7% Toning Solution, which is popular for its exfoliating and skin-brightening benefits. It is used as a toner, applied after cleansing and before moisturizing.

Are There Any Side Effects of Using Glycolic Acid?

Common side effects of glycolic acid include redness, irritation, and dryness, especially when first starting to use it.  It is important to start with a low concentration and gradually increase usage.  If irritation persists, discontinue use and consult a dermatologist. 

Always apply sunscreen during the day, as glycolic acid can make your skin more sensitive to UV rays.

How Often Should I Use Glycolic Acid?

The frequency of glycolic acid use depends on your skin type and the product concentration. Beginners should start with 1-2 times per week and gradually increase usage as their skin builds tolerance. 

For some, using glycolic acid every other day or daily may be appropriate, but it’s essential to monitor your skin’s response and adjust accordingly.

Can I Combine Glycolic Acid with Other Skincare Ingredients?

Glycolic acid can be combined with other skincare ingredients, but caution is needed.  Avoid using it with other strong acids, retinoids, or exfoliating agents to prevent over-exfoliation and irritation. 

Combining glycolic acid with hydrating and soothing ingredients like hyaluronic acid and niacinamide can help mitigate potential dryness and irritation.

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