17 Virginia men suffer dangerously low blood sugar after using over-the-counter sexual enhancement supplements
Health experts have often warned that over-the-counter products sold as dietary supplements might contain undeclared Food and Drug Administration (FDA)-approved prescription pharmaceuticals that could pose a substantial health risk to people who believe them to be harmless. A study now reveals that 17 men in Virginia, US, developed dangerously low blood sugar after taking a male sexual enhancement supplement, which was sold over-the-counter and was laced with prescription drugs.
The blood sugar levels in the 17 patients ranged from 11 milligrams per deciliter (mg/dL) to 66 mg/dL. A normal blood glucose level is between 70 to 100 mg/dL. Samples of the supplement tablet marketed as "V8" were obtained and they were tested. The laboratories confirmed that all tablet samples contained sildenafil (the active ingredient in Viagra) in amounts ranging from 55 to 156 mg per tablet and that most tablets contained 90 to 100 mg of glyburide, a dose 5 to 10 times higher than that used in the treatment of diabetes.
“An unlabeled, over-the-counter product sold in Virginia convenience stores as a male enhancement supplement contained sildenafil and glyburide, a potent hypoglycemic agent, leading to life-threatening episodes of hypoglycemia requiring prolonged hospitalization among users,” say researchers in their analysis in the Morbidity and Mortality Weekly Report of the US Centers for Disease Control and Prevention (CDC). Hypoglycemia is a condition in which the blood sugar (glucose) level is lower than normal.
“Numerous tainted sexual enhancement products remain on the market as over-the-counter products, placing consumers at risk for unknown health complications. Collaborative and timely surveillance and prompt intervention are required to remove products known to cause substantial morbidity,” the team warns. It includes experts from the University of Virginia School of Medicine, Virginia Commonwealth University Health System, Virginia Department of Health (VDH), and Virginia Department of General Services.
The investigation
In August 2019, the Virginia Poison Center (VPC) and the Blue Ridge Poison Center (BRPC) were contacted concerning patients experiencing repeated episodes of marked hypoglycemia following the ingestion of 'V8'.
The first case was reported on August 13, 2019. The VPC was consulted by an emergency physician at an academic medical center about a 57-year-old man, who did not have diabetes and was noted by his wife to have been "diaphoretic (excessive sweating) and agitated" the previous day. His symptoms initially resolved after eating lunch but returned later in the day, and he became increasingly agitated. “After 12 hours of confusion, he was evaluated in a hospital emergency department, where a basic metabolic panel revealed blood glucose of 48 mg/dL. His mental status returned to baseline following administration of intravenous dextrose and 100 mg of octreotide, a drug that inhibits insulin release and is used as an antidote for recurrent hypoglycemia associated with sulfonylurea toxicity,” says the report.
The man had no known exposure to insulin or other hypoglycemic medications but disclosed recently using V8. He purchased the oral supplement from a local convenience store in the metropolitan Richmond area. “He had been unable to fill his usual prescription for sildenafil (used to treat erectile dysfunction) because of health insurance difficulties and reported ingesting one V8 tablet nightly during August 10-12. The treating physician and poison center suspected sulfonylurea poisoning after a literature review noted a 2009 outbreak of hypoglycemia associated with contaminated counterfeit sildenafil. A sample of the V8 product was collected for testing,” says the research team.
On August 22, BRPC was notified about a managed 50 years in Lynchburg, Virginia, who did not have diabetes and who was sweating abnormally and was confused. The local emergency medical services team found his blood glucose to be 32 mg/dL, and he was given oral glucose. On arrival to the emergency department, his blood glucose level was in the normal range, but hypoglycemia recurred 1 hour later. “He was admitted to a hospital, where his overnight blood glucose levels dropped as low as 42 mg/dL despite the intravenous infusion of dextrose-containing fluids and frequent dextrose boluses. He required hospitalization for 3 days for recurring episodes of hypoglycemia,” shows analysis. The patient reported no use of insulin or other hypoglycemic medications. He, however, said that he recently used 'V8' supplement, which he bought from a local service station in Lynchburg.
During the 3 months following the identification of the first two cases, the Virginia Department of Agriculture and Consumer Services (VDACS) and the Virginia Department of Health conducted an investigation and identified 15 more patients who took V8 between August and November 2019. The case definition to identify such patients was severe hypoglycemia within 48 hours of consuming an over-the-counter male enhancement supplement in a man with no history of use of insulin or other medication used to control blood glucose. The 15 additional patients -- men in the age group of 33 to 73 years -- were also hospitalized for management of hypoglycemia associated with taking V8. The mean blood glucose level for all confirmed cases at the initial evaluation was 30 mg/dL, and the lowest documented level was 11 mg/dL. Three patients had two separate hospitalizations each for recurring hypoglycemia related to the use of the supplement.
No V8-related deaths were identified. Patients reported that the V8 supplement was sold in service stations and convenience stores in clear jars without an ingredient list or warning label. The blue tablets found inside closely resembled prescription sildenafil. Patients reported that the supplement was promoted by word of mouth and was purported to enhance male sexual performance.
Besides testing the tablets, blood from three patients was analyzed for the presence of glyburide, and all three tested positive. Glyburide and sildenafil were detected in the urine of a fourth patient. “It is unclear why glyburide was used in the manufacturing of this supplement. It has been hypothesized that the glyburide was added as an available filler. However, given that the tablets contained sildenafil doses within the typical therapeutic dosing range, the inclusion of glyburide as a filler appears less likely. Alternatively, glyburide may have been used to color the tablet blue to resemble prescription sildenafil,” say experts.
What action was taken?
To stem this outbreak, V8 was removed from stores when found, and public service announcements were released. The VDACS investigation into retail facilities resulted in product seizure at 23 locations across Virginia. An FDA investigation into the origin of these products is ongoing. “On August 22, 2019, VDACS released an initial public service announcement to warn consumers of potentially life-threatening hypoglycemia associated with the use of V8 supplements. Follow-up announcements were released by BRPC on August 26 and September 12, urging consumers not to use the V8 supplement. On September 16, VDH posted a notification to other states on CDC’s Epidemic Information Exchange,” says the report.
According to the research team, the public health implications of V8 use include the potential for substantial illness from hypoglycemic episodes and the potential for death if healthcare services are not accessed promptly when hypoglycemia occurs. This outbreak has major implications for public health because consumers might purchase and use these supplements without awareness of the potential for substantial morbidity, they explain.
“Prompt response to the outbreak and collaboration among multiple partners likely resulted in more rapid control of the outbreak and protection of the public from greater harm. V8 supplements and other similar products pose a serious risk for injury to consumers, illustrating an emerging risk associated with tainted male enhancement products,” says the team. They add, “V8 and other male enhancement supplements containing undeclared FDA-approved prescription drugs should be removed from the market expeditiously once identified, and further efforts should be made to educate consumers and clinicians about the potential dangers of over-the-counter products sold with undeclared prescription ingredients.”