Phytanic Acid · What Is It, What Foods Contain It, and More

Phytanic acids are branched chain fatty acids that mainly come from the breakdown of chlorophyll in the human diet, as they are not naturally produced by the human body. Fatty acids are the simplest form of fats in the human body and have many important functions, such as fat storage.  

Phytanic acid doesn’t have any well-defined physiological roles in the human body like omega-3 or omega-6 fatty acids do, but it does have some bioactive properties, like regulating fatty acid metabolism and energy balance. Its importance lies in the fact that excessive amounts are toxic for the nervous system.  

Phytanic acid accumulation most commonly occurs in the setting of Refsum disease, a rare neurologic disorder characterized by numbness and weakness in the arms and legs. Most frequently, Refsum disease is due to a genetic mutation in the gene for phytanoyl-CoA α-hydroxylase (PHYH), which is involved in the metabolism of phytanic acid. Less frequently, it can be caused by a mutation of the gene for peroxin 7 receptor protein (PEX7).  

Both mutations are typically inherited in an autosomal recessive pattern, meaning an individual must inherit a copy of the mutation from each parent to develop the condition. 

PHYH and PEX7 are responsible for the breakdown, or metabolism, of phytanic acid to pristanic acid. The metabolism of phytanic acid occurs by a unique process known as alpha-oxidation, which differs from the more common beta-oxidation of fatty acids. Alpha-oxidation occurs in the peroxisome of the cell, which is a membrane-bound organelle responsible for the breakdown of many molecules, including certain fatty acids and amino acids. The genetic mutation that occurs with Refsum disease alters the peroxisome’s ability to break down phytanic acid, eventually causing the body to accumulate large stores of phytanic acid in the blood and tissues, including the nervous system, retina of the eye, skin, and heart.  

Ultimately, excess phytanic acid prevents proper growth and function of the myelin sheath, which is the fatty layer that surrounds nerves and protects them from damage. 

Peripheral polyneuropathy is one symptom of excess accumulated phytanic acid. Peripheral polyneuropathy describes damage to the peripheral nerves, which causes muscle weakness and a loss of feeling in arms and legs. Muscle weakness is often evidenced through foot drop, which is when the toes drag on the ground when walking.  

Uncoordinated movements due to damage to the cerebellum, called cerebellar ataxia, is another common symptom. Some individuals with accumulated phytanic acid develop retinitis pigmentosa, the loss of cells in the retina, or the back of the eye, which impairs their ability to see peripherally, especially at night.  

Less common symptoms may include anosmia (i.e., loss of smell), sensorineural hearing loss, ichthyosis (i.e., dry, rough skin), and cardiac conduction abnormalities (i.e., problems with the electrical system of the heart that can cause chest pain and fainting). Additionally, infants with Refsum disease often have an orange-yellow color on their teeth. Though symptoms can occur at varying ages, they typically begin between the ages of 10 and 20 and progressively worsen with time. 

Refsum disease is usually diagnosed through a thorough assessment of signs and symptoms, review of medical history, and physical examination. Typically, a blood sample can be analyzed for the presence of elevated levels of phytanic acid in the blood. A diagnosis of Refsum disease often requires confirmation of a genetic mutation in PHYH or PEX7 genes. Nerve conduction studies, which use electrical signals to test responsiveness of nerves, may be conducted to determine the severity of an individual’s case. Finally, a nerve biopsy, when a small segment of nerve is taken from the leg or arm, may be examined to assess the severity of nerve damage. 

Refsum disease is typically treated with dietary changes, particularly avoiding foods containing phytanic acid. An individual with Refsum disease will often be referred to a dietician who can assist in navigating the new diet. Genetic counseling may be helpful for the individual and their family in order to understand the genetic risk of Refsum disease in other family members. If symptoms are severe, plasmapheresis, or blood filtration, may be performed to decrease the level of stored phytanic acid.