Learning from The Past

Toxicological Intimations from The Life and Works of Vincent Van Gogh

While his art is now highly renowned and eulogized, Vincent Willem Van Gogh spent his lifetime in considerable obscurity, fraught with numerous unprofitable endeavors, misfortunes and various illnesses leading up to his ultimate suicide at the age of 37. Years of extensive research into the possible ailments that plagued Van Gogh near the end of his life have revealed several factors that could have contributed to both his physical symptoms as well as the art style of his paintings.

van gogh
Vincent Willem Van Gogh - 1853-1890


Much of Van Gogh’s neuropsychiatric symptoms, most notably his episodes of seizures, began around the time of his move to the city of Arles in southern France. While the pathology of his seizures has been most famously described by Henri Gastaut (1) as a form of temporal lobe epilepsy, the cause of his disorder remains uncertain. While it is reasonable to point to his poor diet and excessive alcohol consumption as the primary factor for his symptoms, a look into Van Gogh’s substance abuse indicates the possibility of several other causes for his convulsions.

  • Absinthe

    Dr. Hemphill (1961) was the first psychiatrist to link absinthe to Van Gogh’s illness (2). Absinthe is an alcoholic drink that became largely popular around the time of Van Gogh’s move to Paris. Traditionally, it comprises anise, fennel, wormwood and various herbs that undergo distillation. However, it is perhaps most popularly known for its supposed hallucinogenic properties, attributable to the chemical component Thujone. While the oil of wormwood is also known to have some convulsant properties (3), the majority of seizures that occur from consumption of absinthe are likely due to the toxic properties of Thujone. In the year 2000, it was revealed that Thujone possesses the ability to block the γ-aminobutyric acid type A (GABA A) receptor chloride channel (4). GABA works in the human body as a neurotransmitter that inhibits brain cell firing. Binding of GABA to its target receptor causes the influx of Chloride ions into cells, thereby producing inhibitory effects that most commonly cause sedation. Whereas anticonvulsant, sedative and anesthetic medication commonly stimulate the GABA receptor, Thujone antagonizes its effects, resulting in the increased excitation of brain cells that predisposes the body to seizures. Hemphill 1961 noted that, not only was Van Gogh’s consumption of absinthe excessive even by normal standards at the time, he was, in fact, more sensitive to its detrimental effects. To add further insult to injury, the continued use of absinthe during this time caused Van Gogh to develop pica. Pica, usually the consequence of a nutritional disorder, causes individuals to crave the consumption of items that are not considered a source of nutrition (e.g. stones, dirt, hair, paint, etc). The phenomenon usually occurs as a result of need-determined behavior secondary to malnutrition (5). Van Gogh’s pica involved a specific predilection toward consuming ‘turpene’ chemicals such as camphor and turpentine oils.

  • Camphor

    Wilfred Niels Arnold, a biochemist who analyzed the mental health and lifestyle of Vincent Van Gogh (6), connected several of Van Gogh’s odd habits to substance use. While he was hospitalized for having cut off his ear in 1888, the artist suffered from insomnia. In an effort to ameliorate his symptoms, reports suggest that he frequently placed camphor under his pillow to help him fall asleep. In addition to this, as described above, he also routinely ingested the substance as a consequence of his pica disorder. Although originally extracted from the barks of the Cinnamomum camphora tree, camphor is now produced only synthetically from components in turpentine and is found in non-prescription products such as lip balms, skin coolers (Vicks VapoRub) and various creams for muscle aches. During Van Gogh’s time, the substance was likely procured in an oil-based form that he both ingested and used topically. The mechanism of toxicity of camphor is unknown, but it has been associated with depression of the Central Nervous System, producing signs and symptoms such as confusion, hyperreflexia, headache, agitation and seizure. (7)

  • Turpentine

    With his increasing psychosis and advanced disease, Van Gogh’s odd consumption habits eventually extended to turpentine oils in the year 1889. Primarily attributed to his pica, Van Gogh was noted to drink the essence of turpentine as well as chew on his oil colors. Turpentine oils, produced by distilling the resin obtained from trees (mainly pine trees), are comprised of chemicals known as turpenes, most notably pinene. Inhalation of large quantities or ingestion of the compound has been shown to produce convulsions, gastric irritation, dizziness, agitation, cyanosis, coma and even death in patients. (8)

Vision Changes

Speculation exists surrounding the influence of drugs on Van Gogh’s vision. Though most authors now believe this to be a mostly unfounded connection, the predominant use of yellow (Figure 1) coupled with halo-like patterns (Figure 2) observed in some of Van Gogh’s later works have often been attributed to toxicity from digitalis.
Figure 1 – ‘Wheatfield With a Reaper’, 1889 - The abundance of yellow color in paintings such as this one has been said to have been associated with yellow vision seen with Digitalis toxicity
Figure 1 – ‘Wheatfield With a Reaper’, 1889 - The abundance of yellow color in paintings such as this one has been said to have been associated with yellow vision seen with Digitalis toxicity
Figure 2 – ‘The Starry Night’, 1889  - Turbulent flows and spirals used to represent stars have been linked to  ‘visual halos’ infamous in Digitalis toxicity
Figure 2 – ‘The Starry Night’, 1889  - Turbulent flows and spirals used to represent stars have been linked to  ‘visual halos’ infamous in Digitalis toxicity

While researchers believe there to be very little evidence of digitalis use in Van Gogh’s life, the association, at the very least, provides a useful mnemonic for medical students to familiarize themselves with the vision changes related to digitalis toxicity.

  • Digitalis

    Digitalis is a cardiac glycoside that primarily acts on the cardiac myocyte by inhibiting the Na+/K+ ATPase pump (outlined in Figure 3). Under normal conditions, this pump acts to exchange intracellular Na+ for K+. Therefore, blocking its activity results in an accumulation of intracellular Na+, which then allows the adjacent Na+/Ca2+ exchange channel to use the excess intracellular Na+ to bring in more Ca2+, resulting in a net increase in intracellular Ca2+ which acts as an inotrope for the cardiac cells.

Figure 3 – Mechanism of action of Digoxin/Digitalis on cardiac myocytes
Figure 3 – Mechanism of action of Digoxin/Digitalis on cardiac myocytes

Digitalis is said to purport its effects on vision through a similar mechanism. In this case, acting on Na+/K+ ATPase channels in the retina results in changes to the arrangement of rods and cones, thereby propagating the symptoms of ‘Xanthopsia’- a term used to describe a distortion in color perception with a tendency toward visualizing colored halos.

The presumption that Van Gogh was exposed to digitalis arose from the fact that, during those times, digitalis (extracted from the plant species, known commonly as the foxglove) may have been used to treat epilepsy. In fact, a plant resembling the foxglove was noted in Van Gogh’s portrait of his psychiatrist (Figure 4).

Figure 4 – Portrait of Dr. Gachet - Dr. Gachet, the psychiatrist, supposedly charged with the treatment of Van Gogh’s Epilepsy is seen painted here with a flower that intriguingly resembles the foxglove plant (from which Digitalis is derived)
Figure 4 – Portrait of Dr. Gachet - Dr. Gachet, the psychiatrist, supposedly charged with the treatment of Van Gogh’s Epilepsy is seen painted here with a flower that intriguingly resembles the foxglove plant (from which Digitalis is derived)

Worsening Mental State

Finally, great debate exists surrounding the cause for Van Gogh’s worsening mental state during the last years of his life. While everything from malnutrition to Acute Intermittent Porphyria has been implicated in the development of his cognitive decline, an interesting toxicological cause that may have been, at least in part, a culprit for his condition is lead poisoning.

  • Lead Poisoning

    The prevalence of lead-based paints in those times, coupled with Van Gogh’s peculiar consumption of oils and paint (pica), suggests both inhalation and ingestion as possible routes of lead exposure for Van Gogh. While exposure does not necessarily confirm poisoning in this case, some of Van Gogh’s evident neuropsychiatric decline does match the psychotic features associated with lead poisoning (also referred to as ‘Saturnism’). An outline of common manifestations of lead poisoning is mapped below (Figure 5)

Figure 5 - Features of lead poisoning
Figure 5 - Features of lead poisoning


Since most of the information obtained on Van Gogh’s illness is extracted from unreliable accounts and excerpts of letters he wrote toward the end of his life, any causal association, toxicological or otherwise, would ultimately be pure conjecture. At the very least, however, the relations outlined above provide an educational insight into the possibilities and mechanisms by which the substances prevalent in Van Gogh’s lifestyle could, in part, be contributory to his tendencies and even his psychiatric disease.

References and Further Reading

  1. Gastaut H: La maladie de Vincent van Gogh envisagée a la lumière des conceptions nouvelles sur l épilepsie psychomotrice. Ann Méd Psychol (Paris) 1956; 114:196–238
  2. Hemphill RE (1961): The illness of Vincent van Gogh. Proc Roy Soc Med 54: 1083–1088
  3. Simonetti G. Simon & Schuster’s Guide to Herbs and Spices. New York: Simon & Schuster; 1990. pp. 261–262
  4. Hold K M, Sirisoma S I, Ikeda T, Narahashi T, Casida J E. Proc Natl Acad Sci USA. Alpha-thujone (the active component of absinthe): gamma-aminobutyric acid type A receptor modulation and metabolic detoxification. 2000;97:3826–3831
  5. Richter CP. Self-selection of diets. Essays in Biology. Berkeley, CA: University of California Press; 1943
  6. Vincent van Gogh: chemicals, crises, and creativity, Author: Wilfred Niels Arnold, Published by Birkhäuser, 1992
  7. Phelan WJ, 3rd. Camphor poisoning: over-the-counter dangers. Pediatrics 1976; 57:428–431, Klingensmith WR. Poisoning by camphor. J Am Med Assoc 1934; 102:2182–2183
  8. Pande TK, Pani S, Hiran S, Rao VVB, Shah H, Vishwanathan KA (1994) Turpentine poisoning: a case report. Forensic Sci Int 65: 47–49

A Case Of Cyanide Poisoning From Vitamin B17

Since their advent in the 1930s, ‘vitamin pills’ have shown a steady rise in both variety and consumption patterns in patients. Guided by the promise of a healthier lifestyle and overall wellness, the use of vitamin supplements has become increasingly commonplace and you would be hard-pressed to find a patient who isn’t on some form of regular vitamin. Most of these nutritional adjuncts are either indicated for chronic conditions or, at the very least, harmless additions to daily regimens and do not usually warrant a second thought when described during patient encounters in the ED. However, not all supplements are as benign as they might seem. The following case report details the events that unfolded when a 45-year-old male patient accidentally ingested more tablets than were indicated for a vitamin he had purchased online.

Case Presentation

A 45-year-old male presented to the Emergency Department with complaints of fatigue, shortness of breath and anxiety following a possible over-ingestion of vitamin supplement tablets. As per the patient, he ordered a bottle of vitamin supplements online and admitted to misreading the instructions on the label. Instead of the recommended one tablet per day dose, he reported taking eight tablets for the first time earlier that morning. The tablets were bought without the need for prescription and, according to the patient’s research, were meant to be “good for promoting long life and preventing cancer.” Upon arrival to the ED, the patient was visibly anxious and mildly diaphoretic, stating that “I know I took too many tablets. Am I going to be okay?”

Physical Exam

Examination revealed a tired-looking patient with vital signs significant only for mild tachycardia of 105 and spO2 95% on room air. Otherwise, physical exam was normal. 


The initial ABG and preliminary lab tests revealed no significant findings, mildly elevated lactate of 1.8, for which the patient was placed on fluids with observation.

Being a particularly busy shift at the Emergency Department, the patient’s presentation coupled with his history of seemingly harmless vitamin ingestion, did not produce an immediate cause for concern. Nevertheless, he was monitored frequently until his investigations returned, during which time he remained clinically stable and without any subjective complaint besides a persistent feeling of fatigue.

A second ABG was performed and, despite the fluids, demonstrated a rise in his lactate levels to 2.6. By this time, the patient’s companion had made their way to the hospital, carrying with them the bottle of pills he reported he took prior to the onset of his symptoms. The bottle of supplements was filled to about ¾ of its capacity, with the label indicating that each capsule contained 250mg of Vitamin B17.

Given the persistence of fatigue and rising lactate, the physician decided to perform an internet search on whether any adverse effects were linked to the over-ingestion of vitamin B17. While most sources claimed the supplement was relatively safe, with many ayurvedic webpages praising the vitamin’s numerous benefits, it was soon found that the vitamin had been shown in studies to be associated with the development of cyanide toxicity when taken in large amounts.

However, this toxicity apparently only seldom manifested in individuals who only consumed vitamin B17. Instead, the cases of cyanide toxicities observed occurred more frequently in groups of patients who had concomitant consumption of Vitamin C.

Returning back to the patient, further history taking revealed that the patient had, in fact, consumed vitamin C for the past one month after he had about flu and had failed to mention it earlier as it had ‘slipped his mind at the time.’ Considering the risks evident in the patient’s ingestion history and his worsening fatigue (at 30 minutes after the ED arrival, the patient had now become increasingly somnolent with profuse diaphoresis, maintaining O2 saturation at 94-96% on room air), the decision was made to manage the patient as a case of cyanide toxicity and hydroxycobalamin was administered.

What is Vitamin B17?

Vitamin B17, also known as Amygdalin, is a naturally occurring chemical compound that is found most famously in the seeds of fruits such as apricots, bitter almonds, apples, peaches and plum (1). At the molecular level, amygdalin is formed as a chemical combination of Glucose, Benzaldehyde and Cyanide. The cyanide component in amygdalin can be released by the action of Beta-Glucosidase and Emulsin- both of which are not present in human tissues. However, microorganisms present in human intestinal linings have been found to possess similar enzymes that effectively promote cyanide release from the Amygdalin compound. The resulting cyanide toxicity is therefore almost 40 times more toxic by the oral route when compared with IV injection of the compound (2).

A modified form of amygdalin has been available under the brand name ‘Laetrile’ since the early 1950s as an alternative treatment to fight cancer, though most studies have failed to show any such benefit in humans (3). While the US FDA continues to insist on the drug’s obvious cyanogenic effects, there exist numerous advocates promoting the potential benefits of taking Amygdalin. Despite years of regulation on the original Laetrile supplement, unregulated forms of Amygdalin (or Vitamin B17 as it is often called) continue to circulate the market and are available in most outlets without the need for a prescription.

Since the toxicity of amygdalin depends on intestinal conversion, peak levels of cyanide are usually reached at around 2 hours post-ingestion. A curious phenomenon was evidenced in studies which found that the conversion of amygdalin to cyanide in vitro was further accelerated when amygdalin was ingested with foods containing beta-glucuronidase (such as bean sprouts, peaches, celery, and carrots) or with a concurrent intake of high doses of vitamin C (4,5).

Cyanide Toxicity - Principles & Management

Oral intake of 500 mg of amygdalin may contain up to 30 mg of cyanide (6). A minimum lethal dose of cyanide is approximately 50 mg or 0.5 mg/kg body weight (7). Our patient had ingested eight 250mg tablets, totaling 2000mg of amygdalin, thereby exposing him to a dose of cyanide well above the lethal dose.

Cyanide has a famously dangerous mechanism of toxicity. It binds to the ferric ion on cytochrome oxidase in mitochondria and blocks the electron transport chain, thus halting oxidative metabolism and leading to cell death by interfering with mitochondrial oxygen utilization leading to cell death, hypoxia and lactic acidosis (8). Mild to moderate cases of cyanide toxicity manifest as tachycardia, headache, confusion, nausea, and weakness. Severe cases may present with cyanosis, coma, convulsions, cardiac arrhythmias, cardiac arrest, and death.

Treatment involves addressing the patient’s vitals, oxygen saturation and acidosis as well as administering the appropriate antidote as detailed in the Table below. A sequence of these medications can be incorporated or hydroxycobalamin can be administered alone, as was done in the case above.

Cyanide Toxicity Medication



Mechanism of Action


Amyl Nitrite pearls
0.3mL (1 amp) inhaled prior to establishing IV
Induces methemoglobinemia (binds cyanide)
First component of cyanide kit Discontinue once IV started
Sodium Nitrite
300mg (10 mg/kg) IV over 3-5 minutes
Induces methemoglobinemia (binds cyanide)
Second component of cyanide kit Do NOT use if suspected concurrent Carbon Monoxide poisoning
Sodium Thiosulfate
12.5 g IV over 10-20 minutes
Binds cyanide to form thiocyanate (less toxic) which is excreted in urine
Third component of cyanide kit
5 g IV over 15 minutes
Binds cyanide to form cyanocobalamin (Vitamin B12) which is excreted in urine
Can be used as a single agent May cause transient hypertension


As with most cases of toxic ingestion, the key to effective management is appropriate stabilization followed by rapid identification of the potential toxicity through focused history taking and physical examination of the patient. In cases such as the one outlined above, where the ingested agent is unfamiliar but poses a potential threat, efforts should be made to probe deeper into the potential side effects, interactions and toxicities of such drugs and the Poison Control Center contacted immediately when and where available to expedite successful treatment of affected patients.

For our patient, the decision to administer hydroxycobalamin was followed by admission to the ICU with serial investigations done to monitor for any metabolic derangements. The patient showed remarkable improvement in his symptoms over the course of 24 hours and was eventually discharged in a stable condition.

References and Further Reading

  1. National Center for Biotechnology Information. PubChem Compound Database; CID=656516,
  2. https://pubchem.ncbi.nlm.nih.gov/compound/656516
  3. Laetrile (Vitamin B17 or Amygdalin): Benefits, Myths and Food Sources, https://www.healthline.com/nutrition/laetrile-vitamin-b17
  4. Bromley J., Hughes B. G. M., Leong D. C. S., Buckley N. A. Life-threatening interaction between complementary medicines: Cyanide toxicity following ingestion of amygdalin and vitamin C. Annals of Pharmacotherapy. 2005;39(9):1566–1569. doi: 10.1345/aph.1E634
  5. Conjoint use of laetrile and megadoses of ascorbic acid in cancer treatment: possible side effects, 1979 Sep;5(9):995-7, PMID: 522711
  6. Newton G. W., Schmidt E. S., Lewis J. P., Conn E., Lawrence R. Amygdalin toxicity studies in rats predict chronic cyanide poisoning in humans. Western Journal of Medicine. 1981;134(2):97–103.
  7. Shragg T. A., Albertson T. E., Fisher C. J., Jr. Cyanide poisoning after bitter almond ingestion. Western Journal of Medicine. 1982;136(1):65–69
  8. Physician Beware: Severe Cyanide Toxicity from Amygdalin Tablets Ingestion- 2017; 2017: 4289527, DOI: 10.1155/2017/4289527

Lover’s Fracture

A 35-year-old construction worker was brought in by the ambulance to the Emergency Department. He was reported to have fallen from scaffolding at the height of approximately 4 meters and landed onto the concrete floor below feet first. He was found conscious by paramedics but in obvious pain, holding his right leg. Upon initial examination in the ED, the patient remains vitally stable but complains of severe, persistent pain in his right ankle and heel. After adequate analgesia, an X-ray of the right ankle and foot revealed signs of a calcaneal "Lover’s" fracture (Figure 1).

Figure 1
Figure 1: Image courtesy of Annelies van der Plas, and J.L. Bloem - http://www.startradiology.com/internships/general-surgery/ankle/x-ankle/

Calcaneal Fractures

Before we begin our discussion on calcaneal fractures, it is important to highlight the major anatomical structures visible on a standard X-ray of the ankle and foot.

Figure 2
calcaneus and foot anatomy

Figure 2 shows a lateral x-ray of the right ankle, demonstrating the calcaneus as the bone – commonly referred to as the heel – that makes up the majority of the hindfoot.

As would be expected, the size and position of the calcaneus predispose the bone to various forms of injury. A calcaneal fracture is most often sustained after a road traffic accident or a fall from significant height onto the feet as was the case with our patient. Due to the mechanism of injury, it is often colloquially dubbed as “Lover’s fracture” or the “Don Juan fracture”(1).


Among fractures of the hindfoot, calcaneal fractures comprise 50-60% of all tarsal bone fractures (2). These fractures are usually intra-articular (3) and occur more commonly in young men aged between 20 and 40 years. Diseases which decrease bone density, such as osteoporosis, invariably increase the risk for development of the fracture when injury occurs.

Patient evaluation

Patients with calcaneal fractures will often present in severe pain, though they may not always be able to localize the exact source for their pain. Swelling at the ankle or heel along with bruising (ecchymosis) can also be expected. Due to the mechanism of fall, injury usually occurs bilaterally. Most patients are unable to bear any weight onto the affected limb.

The lower extremity or extremities in question should undergo a thorough neurovascular exam, as diminished pulses distal to the injury (dorsalis pedis) could indicate arterial compromise and mandate aggressive investigation with angiography or Doppler scanning. Though the gold standard for diagnosing calcaneal fractures remains a CT scan, a plain film X-ray is usually obtained first which should include an Antero-Posterior (AP), a lateral, and an oblique view.

Bohler’s Angle and Critical Angle of Gissane

Historically, physicians would measure Bohler’s angle and the critical angle of Gissane in cases where a calcaneal fracture was not clearly evident on a plain X-ray. Outlined in Figure 3, a calcaneal fracture would be suspected if Bohler’s angle was below 20 degrees or the critical angle of Gissane was noted to be more than 140 degrees. Bohler’s angle was found to be a lot more diagnostically reliable when compared to the critical angle of Gissane (4). However, both these methods of diagnosis are now considered obsolete and the same research that studied that utility of the angles found that Emergency Physicians were able to accurately identify calcaneal fractures approximately 98% of the time without the measurement of either angle.

Figure 3
853 - bohler angle - calcaneus
854 - Gissane angle- calcaneus

Figure 3- Bohler’s Angle and Critical angle of Gissane


The goal of initial management in the Emergency Department is centered on adequate pain relief, immobilization and wound care (including antibiotics when there are signs of a contaminated wound). [See the link for open fractures and antibiotic choices.]

An important point to note is that the mechanism of injury in calcaneal fractures (namely fall from height) is a form of axial loading. The energy from landing on the ground will often be transmitted up through the body, usually to the spine causing compression fractures of the vertebrae. The patient, however, may not complain about pain in other areas due to the overwhelming and distracting pain in the calcaneus. Therefore, all calcaneal fractures should be managed with a high index of suspicion for associated injuries.

Other potential complications include compartment syndrome, wound infection, malunion and osteomyelitis. All patients diagnosed to have calcaneal fractures should be managed by a multidisciplinary team that includes an Orthopedic Surgeon to ensure definitive management and repair of the fracture.

Take Home Points

  • High energy impact with axial loading, usually from a road traffic accident or a fall from height should raise suspicion of a calcaneal fracture.

  • Perform a thorough evaluation of the site of injury and suspect associated injuries (check the spine and remember to check the other foot for concomitant injury).

  • Maintain adequate analgesia (these fractures hurt!) and involve the Orthopedic Surgeon as soon as the diagnosis is made.

References and Further Reading

  1. Lee P, Hunter TB, Taljanovic M. Musculoskeletal colloquialisms: how did we come up with these names? Radiographics. 2004;24 (4): 1009-27. doi:10.1148/rg.244045015
  2. Davis D, Newton EJ. Calcaneus Fractures. [Updated 2019 Mar 13]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2019 Jan
  3. Jiménez-Almonte JH, King JD, Luo TD, Aneja A, Moghadamian E. Classifications in Brief: Sanders Classification of Intraarticular Fractures of the Calcaneus. Clin. Orthop. Relat. Res. 2019 Feb;477(2):467-471
  4. Jason R. K., Eric A. G., Gail H. B., Curt B. H. & Frank L. Boehler’s angle and the critical angle of gissane are of limited use in diagnosing calcaneus fractures in the ED. American Journal of Emergency Medicine. 24, 423–427 (2006)