Friday, March 11, 2011 12pm-4pm

Where:

Richland Lanes

Why:

To benefit our Wii Wonders consumer activity program

Who:

One representative from each dept. will be bowling, as well as any Wii Wonders consumers that are interested. This event is also open to any Board members willing to participate. What: We are having a penny a pin fundraiser. Each bowler will gather sponsors willing to donate one penny for every pin knocked down in the course of three games.

For Example:

If a bowler bowls a 125 for one game, each sponsor that pledged a penny would owe $1.25 for that game.

If you are interested in participating in any way at all please contact Stacey Zometsky at (814) 262-9600 or szometsky@alucp.org.

Question:

I have an adult patient who has been on antiepileptic drug therapy for many years and still has seizures. We have tried switching AEDs with no success. Is it time to talk about surgery?

Response from Andrew N. Wilner, MD Neurohospitalist, Lawrence and Memorial Hospital, New London, Connecticut

Drug-Resistant Epilepsy

Of the approximately 2 million people with epilepsy in the United States, 400,000 to 600,000 experience seizures despite antiepileptic therapy.^[1] Drug resistance has recently been defined by the International League Against Epilepsy (ILAE) as a “failure of adequate trials of 2 tolerated, appropriately chosen and used antiepileptic drug schedules (whether as monotherapy or in combination) to achieve sustained seizure freedom.”^[2] Drug-resistant patients are unlikely to become seizure-free through participation in future drug trials and should be evaluated for epilepsy surgery.^[3] “Pharmacoresistant” is a synonym for “drug resistant.” Other terms, such as “intractable,” “refractory,” and “uncontrolled” epilepsy are less strictly defined but describe a patient with continued seizures who warrants further evaluation.

Criteria for Surgery

Epilepsy surgery should be considered for patients with drug-resistant seizures if the seizures significantly interfere with their life.^[4] It is not necessary that the patient have daily or even weekly seizures. For example, a school teacher who has 1 seizure a month despite appropriate antiepileptic medication, but who cannot drive to work or supervise her class, may be a good candidate for epilepsy surgery.

Epilepsy surgery is an underused therapy for people with drug-resistant seizures.^[1] Patients are often referred for surgery after 15 years or more of habitual seizures.^[5] This delay allows seizures to chronically interrupt schooling, employment, and social interactions. People with uncontrolled seizures are at increased risk for death (almost 5 times that of the general population) from status epilepticus, SUDEP (Sudden Unexpected Death in Epilepsy), accidents, and other causes.^[6] After successful surgery, mortality rates return to those of the general population.^[7] Patients who have a single epileptic focus in the anterior temporal lobe are the most amenable to successful epilepsy surgery.

Benefits of Surgery

Approximately two thirds of patients with temporal lobe epilepsy achieve surgical success (are free of disabling seizures) after temporal lobectomy.^[4] A randomized, controlled clinical trial demonstrated that surgery for temporal lobe epilepsy was superior to continued medication trials in drug-resistant patients to achieve seizure control and improve quality of life.^[8]

Epilepsy surgery should be performed at an epilepsy center, where patients can be evaluated by a multidisciplinary team that includes, at a minimum, an epileptologist, a neuropsychologist, a neuroradiologist, and a neurosurgeon. Patients with epilepsy are likely to have medical and psychiatric comorbidities, and these need to be addressed as well in the presurgical and postsurgical settings.^[9] Other team members such as a neuropsychiatrist, epilepsy nurse coordinator, and social worker can help provide more comprehensive care. Benefits and risks must be weighed for each patient with respect to the safety of the surgery and likelihood that the patient will become seizure-free.

Summary of Considerations

Epilepsy surgery has been underused and should be considered in drug-resistant patients.^[10] Patients with drug-resistant epilepsy should be promptly referred to a comprehensive epilepsy center to determine whether they are likely to benefit from epilepsy surgery.^[5] Other therapies for drug-resistant epilepsy, such as the vagus nerve stimulator, may also be considered, but vagus nerve stimulation is rarely curative.^[7] A ketogenic diet may also be tried, but its success has mostly been in children. Successful epilepsy surgery can minimize the risk for injury and death from uncontrolled seizures and prevent the acquired psychosocial disabilities of a lifetime with epilepsy.

National trends in the treatment for depression from 1998 to 2007

Marcus SC, Olfson M.
Arch Gen Psychiatry. 2010;67:1265-1273.

Summary

This is a report of service utilization data from 2 large nationally representative surveys of the US population. The authors measured rates of depression treatment, use of antidepressant medication and psychotherapy, and the number of outpatient treatment visits and expenditures. The authors found that the rate of outpatient treatment for depression increased from 2.37 per 100 persons in 1998 to 2.88 per 100 persons in 2007. The percentage of treated patients who used antidepressants changed little — from 73.8% in 1998 to 75.3% in 2007 — but the percentage of those receiving psychotherapy declined from 53.6% to 43.1%. National expenditure for outpatient treatment of depression increased from $10.05 billion to $12.45 billion, primarily due to an increase in medication expenditures from $4.59 billion to $6.60 billion but also because of an increase in Medicare expenditures for depression treatment from $0.52 billion to $2.25 billion.

Viewpoint

Depression is common and can be debilitating. Fortunately, effective treatments are now available, and for the most part they are easy to prescribe and are well-tolerated. It is not a surprise that with the advent of serotonin-specific reuptake inhibitors the percentage of Americans treated for depression increased from 0.73% in 1987 to 2.33% in 1997, and that among these persons, antidepressant medication use increased from 37.3%-74.5%. The authors update these data with information about changes from 1998-2007. Antidepressant medication use has remained the same among treated persons, but psychotherapy is less commonly utilized. The rate for psychotherapy among persons treated for depression in 1987 was 71.1%; 2 decades later it was 43.1%.

Psychotherapy demands an investment of time and money and is not as easily accessible as medication treatment that can be provided by primary care clinicians. For persons with insurance, finding a “panel psychiatrist” available to see them is a challenge in itself — finding one that will also provide a combination of psychotherapy and pharmacotherapy is nearly impossible in many communities. Going “out of network” is not financially feasible for many patients. Indeed, I am surprised that the rate of psychotherapy is as high as it is.

The authors do note that the rate of outpatient treatment for depression of 2.88 per 100 persons in 2007 remains far below the estimated rate of depression in the community. More work is needed for all of us to improve recognition of major depressive disorder, lessen its stigma, and increase access to treatment.

Background

Human scabies is a debilitating skin disease caused by Sarcoptes scabei, known by several names such as “itch mite.” At any given time, the worldwide burden of disease is about 300,000,000 people. It is an arthropod infestation primarily affecting impoverished populations. Ordinary scabies is treated with permethrin-based creams and shampoos while crusted “Norwegian” scabies is often treated with a combination of permethrin (5%) and oral ivermectin 200 µ/kg. Antibiotics are used when there is a secondary bacterial skin infection usually resulting from the excoriation of scratching and compromise of the integument by the mites themselves.

Methods

Strong and Johnstone^[1] recently updated the Cochrane Database on this topic last reviewed by this group in 2000. The objective was to compare extant literature on topical and oral interventions. The authors searched the Cochrane Infectious Diseases Group Specialized Register, MEDLINE, EMBASE, INMED and others to find randomized, controlled trials of drug treatments for scabies. Additionally, they searched reference materials from the retrieved studies and ongoing, registered trials.

Results

The authors found twenty trials with a total of 2392 participants. The most commonly studied compounds were the pyrethrins, ivermectin, lindane, sulfur and benzyl benzoate. No serious adverse effects were reported in any study of topical or oral agents used to treat ordinary scabies or crusted scabies.

Conclusions

The authors concluded that topical permethrin and oral ivermectin are the most effective treatments for scabies.

Relevance to Emergency Medicine

Most emergency physicians are familiar with topical treatments for scabies such as those containing permethrin (e.g. Elimite). Oral agents are not commonly used in the United States either because medications such as ivermectin aren’t on formulary or because physicians are not familiar with this strategy of scabies management. Many compounds with proven or suspected acaricidal activity have been tried since antiquity. In the 20^th century and in this century, ivermectin has been used safely in millions of people to eradicate diseases such as river blindness caused by Onchocerca volvulus and to treat common parasitic diseases such as filiariasis. Ivermectin (200 µ/kg) has been effectively used in single doses and in doses separated by 10 days to control scabies.^[2]Further studies need to be performed in institutional and community settings, but physicians should consider this cost effective treatment and clinically effective treatment in patients who are allergic to permethrin formulations or in those who are not likely to follow through on their treatment plans if given a prescription for topical formulations. Ivermectin typically comes in 6 or 12 mg scored tablets.

Nearly 70% of HIV-infected homeless or marginally housed individuals receiving tenofovir/FTC/efavirenz demonstrated virologic suppression at 6 months.

Introduction

Many HIV-infected populations, including the homeless, are thought to have less than optimal treatment adherence and to therefore be at increased risk for virologic failure and antiretroviral resistance. Such populations may benefit from simpler regimens, such as the once-daily single-pill regimen consisting of tenofovir/FTC/efavirenz (Atripla), but this hypothesis has not been well studied.

In a recent observational study (partially funded by the makers of tenofovir/FTC/efavirenz), researchers evaluated rates of treatment adherence and virologic suppression among 118 homeless or marginally housed HIV-infected patients in San Francisco: 47 who received tenofovir/FTC/efavirenz and 71 who received standard regimens that have a higher pill burden and/or require greater dosing frequency. Most of the study participants were men (73%), were not white (61%), and had a history of injection drug use (63%). Adherence was monitored for 6 months using unannounced pill counts, and then viral loads were determined.

Mean adherence levels were significantly higher with tenofovir/FTC/efavirenz than with other regimens — 86% versus 73% — even after adjustment for sex, race, education, income, homelessness, injection drug use, nadir CD4-cell count, depression symptoms, prior ART use, and calendar year. Rates of virologic suppression at 6 months were also significantly higher with tenofovir/FTC/efavirenz than with other regimens — 69% versus 46%.

Comment

This study highlights that a once-daily single-pill antiretroviral regimen can lead to successful virologic suppression among homeless or marginally housed individuals. Presumably, patients who move frequently or lack private space find the lower pill burden much easier to manage. One limitation of this study is that investigators did not determine resistance mutations among patients who did not achieve virologic suppression. Thus, when considering tenofovir/FTC/efavirenz, a provider must still weigh the risk of resistance if the patient is not adherent against the potential benefit if he or she is.

Community Aging, Assisted Living and Long Term Care (CAALLTC) Essentials is a 1.5 day live program that introduces attendees to the opportunities of providing long-term care services and the business efficiencies necessary for success.

Supplying medications to LTC facilities and offering senior care services are not synonymous. Your services may initiate simply by supporting caregivers who need your assistance so their loved ones can remain independent and in their homes as long as they wish. Attendees will learn about senior care settings, useful workflow, packaging and inventory management tools, and how to market your pharmacy services to facilities in a manner that distinguishes you from the competition.

Are you new to the space?

CAALLTC “Essentials” is an entry-level program designed for pharmacists who wish to begin offering senior care pharmacy services to group homes, adult day care and assisted living facilities, retirement communities and hospice.
Note – This program is NOT for advanced practitioners providing pharmacy services to LTC facilities (nursing homes, skilled nursing facilities)

Become extraordinary – CAALLTC “Essentials”

The 2011 CAALLTC Essentials Programs will be held:

February 26-27: Richmond, Virginia
October 6-7: Nashville, Tennessee (Preconvention program prior to 2011 Annual Convention)

Program Length
The CAALLTC Essentials program will provide each participant up to 11.25 contact hours of continuing pharmacy education (1.125 CEUs).

Abstract and Introduction

Abstract

Severe acne may increase risk for suicide, and isotretinoin might exacerbate the risk.

Introduction

Although isotretinoin has been anecdotally linked to suicide, observational studies have had inconsistent results. In other studies, severe acne itself increased risks for distress and suicide. In this retrospective cohort study of 5756 patients prescribed isotretinoin for severe acne in Sweden, researchers examined administrative data documenting suicides and hospitalizations for suicide attempts for 3 years before and up to 18 years after treatment (1980–2001).

Isotretinoin treatment lasted a mean of 6 months. In the 21-year period, 128 patients attempted suicide and 24 died by suicide. Rates of suicide attempts rose in the year before treatment was initiated (standardized incident ratio [SIR]: any attempt, 1.57; first attempt, 1.36), increased significantly within 6 months after the start of treatment (SIRs, 1.78 and 1.93, respectively), and returned to baseline by year 3 posttreatment. Compared with patients whose first attempts occurred before isotretinoin therapy, those whose first attempts occurred during treatment or within 6 months of cessation were significantly more likely to make a second attempt or die by suicide (38% vs. 71%). Rate differences before and after the start of treatment yielded a number needed to harm (NNH) of 2300 for a new suicide attempt and 5000 for a repeat attempt.

Comment

Having severe acne may be a risk factor for suicide, given that attempt rates increased before isotretinoin was initiated. The further increase in rates after isotretinoin initiation indicates that the medication could heighten the risk, but this study had no control group to firmly establish this. Isotretinoin recipients with previous attempt histories had a lower rate of subsequent suicide attempts than patients whose first attempts occurred in connection with treatment. Thus, a suicide attempt history does not seem to contraindicate isotretinoin treatment. Still, the results argue for close monitoring of all isotretinoin-treated patients for suicidal behavior for up to a year after treatment stops.

Abstract and Introduction

Introduction

All healthcare organizations have disaster plans in place that they practice and refine in preparation for an unexpected crisis. These plans are not developed “on the fly” because healthcare providers recognize the value of planning for the unexpected and the necessity of minimizing potentially life-saving interruptions in care. The ongoing problem with drug shortages in our nation is rising to the level of “disaster” status. Drug shortages continue to take an enormous toll on healthcare providers who must deal with the problem on a daily basis, and on patients who are on the receiving end of the shortages.

According to more than 1,800 respondents to our recent 2010 survey, the conditions associated with drug shortages during the past year have been the worst ever, with little hope for improvement in the near future. Respondents were most alarmed by:

• The ever-increasing volume of critically important medications in short supply
• The use of less desirable, unfamiliar alternative drugs—if available
• Errors and poor patient outcomes caused by absent or delayed treatment or preventable adverse drug events caused by the use of alternative drugs or dosage forms
• The lack of advanced warnings about impending shortages
• Precious clinical hours lost to time-consuming activities required to manage drug shortages.

Overall, survey respondents conveyed a real sense of crisis and are clearly looking for support to reduce the organizational burden and potential patient harm associated with drug shortages. As previously mentioned, ISMP and the American Society of Health-System Pharmacists (ASHP) believe a public meeting with FDA and key stakeholders is urgently needed to develop a strategic plan aimed at reducing the occurrence of drug shortages and managing them better when they occur. More effective FDA oversight of drug shortages, a comprehensive early warning system, and patient safety and clinical outcomes placed ahead of anyone’s profit margins are goals we hope to begin to explore at this meeting.

Meanwhile, healthcare organizations, guided by pharmacy leadership, can follow the recommendations below to help manage this complex problem. These recommendations are primarily culled from a prior article ISMP published on drug shortages,^[1] ongoing discussions with healthcare providers, and guidelines published by ASHP in 2009.^[2] Some of the recommendations denote well-known and currently followed steps; others may provide new ideas for managing the problem. Either way, the recommendations can serve as a tool to evaluate your current processes for managing drug shortages. Although it may be impractical to prepare for every potential drug shortage, proper planning can minimize the adverse effects on both patients and providers.

Learn More About Drug Shortages

Once an impending or actual shortage has been identified, call the manufacturer for more details about the shortage, its estimated duration, and directions for ordering drugs on allocation or for emergent situations. Wholesalers and purchasing groups may also be a good source of information about drug shortages and alternatives.

Assess Inventory of Drugs on Hand

Begin to assess the impact of the shortage by counting your inventory on hand and estimating how long the supply will cover your needs based on historical usage of the drug.

Research the Drugs in Short Supply

Identify clinically appropriate uses of the drug, the lowest optimal dose for current indications, and strategies to decrease drug waste and inappropriate/unnecessary prescribing. Reference historical data from any drug use evaluation (DUE) conducted in the past or consider performing a DUE to determine how the drug is actually used in your facility.

Identify Potential Therapeutic Alternatives Early

Create and employ a standard, formal process for identifying and approving therapeutic alternatives to shortage drugs. An expedited approval process is also needed when the standard process is not timely enough to meet needs based on current inventory of the shortage drug. Obtain suggestions for therapeutic alternatives from the literature, professional websites, listserves, prescribers who use the product, and other local/regional hospitals (to promote consistency for prescribers who practice at multiple sites). Ensure that any decisions made about alternative drugs are in collaboration with medical, nursing, and pharmacy representatives, as well as any other disciplines that may use the product (e.g., respiratory therapists); involve a pharmacy and therapeutics committee as appropriate. Select alternatives early so an education plan can be developed in case implementation is needed. When appropriate, develop and approve guidelines for use of the alternative drugs. Also conduct an inventory of the current supply of approved therapeutic alternatives that will be used.

Prioritize Patients and Place Limitations on Use

Based on the extent of the shortage or shortage forecast, availability of alternatives, and results of DUEs, develop temporary therapeutic guidelines that reduce waste and tailor the drug’s use to groups of priority patients for whom the alternative drug may be unsafe, ineffective, or undesirable. Guidance on management of shortages and use limitations may be available from external organizations, such as government agencies (e.g., Centers for Disease Control and Prevention, departments of health [for an example associated with vaccine shortages, visit: www.health.state.mn.us/oep/healthcare/standards.pdf]), medical/professional organizations (e.g., Anesthesia Patient Safety Foundation), and specialty groups (e.g., American Society for Parenteral and Enteral Nutrition). Reassess how long the drug will be available to priority patients after conservation measures have been implemented. When appropriate, remove shortage drugs from unit floor stock and have pharmacy dispense the drugs as needed to better control use and waste.

Conduct a Failure Analysis and Take Action

Considering the medical necessity of the shortage drug, the duration of the shortage, and the current supply of the drug, assess the potential hazard to patients and the organization. Conduct a mini failure mode and effects analysis (FMEA) to identify required changes to processes and potential misuses of alternative products. (A sample format for a mini FMEA from OhioHealth Pharmacy Services is available below) Determine how to best manage the risk of serious errors and adverse reactions to alternative drugs, and take action. Consider how the use of alternative drugs could affect current prescribing practices, storage of the drug, final product preparation (including directions for admixing), drug administration procedures, and the use of technology (e.g., electronic prescribing, bar-coding systems, automated dispensing cabinets, smart pump libraries). Make any necessary procedural and technological changes to support safe use of the alternative medications. Whenever possible, have pharmacy prepare and dispense alternative drugs in the most ready-to-use form. Also address any sound- and look-alike issues with an alternative drug’s name and packaging, and determine if additional safety checks, alerts, and/or patient monitoring are required when prescribing, preparing, dispensing, and administering an alternative product Table 1.

Do not Hoard Shortage or Alternative Drugs

Stockpiling a medication may lead to an artificial shortage where the drug might otherwise be available in adequate supplies to meet patient needs across the nation. Further, manufacturers with products in short supply rarely honor requests for quantities larger than historically ordered; allocations to organizations are typically determined by prior use.

Establish Ongoing Communication with Staff

Using the most effective means possible (e.g., staff meetings, newsletters, email, website, Intranet, posters/charts, alerts in electronic systems), regularly share information with clinicians about:

• The drug shortage, causes, and expected duration (if known)
• Assessment of current drug availability
• Temporary therapeutic guidelines, including use limitations for the shortage drug
• Alternative products and how they will be supplied to units
• Dosing, preparation, and administration guidelines for alternative products
• Error potential with alternative products and how to reduce risk
• Additional patient monitoring and safety steps that may be required when using an alternative drug.

Consider preparing a report which includes the above information on the most critical drug shortages, updating the report on a daily basis, and using the report to keep healthcare professionals informed about the shortages (e.g., included in clinical staff email, staff meetings, the organization’s Intranet, newsletters). Pharmacy staff should be briefed daily regarding all aspects of drug shortages so they can serve as a resource to prescribers, nurses, and patients.

Establish a Drug Shortage Network with Other Local Healthcare Providers

Build and strengthen local collaborative networks to share information regarding drug shortages and alternative products, to share emergency supplies of shortage drugs when appropriate, and to coordinate the transfer of patients to providers that still have a shortage drug available when an alternative is not suitable.

Determine an Organizational Position on Alternative Suppliers

The potential availability of shortage drugs from secondary gray markets, compounding pharmacies, or ramped up in-house compounding are complex issues that require philosophical discussions as well as quality and budgetary considerations to determine whether it is appropriate and safe to utilize these resources. Decisions regarding these issues are difficult to make under pressure, so the organizational position should be well known and documented. Requirements regarding quality control measures for outside vendors and criteria for when the current position might be challenged should be included.

Proactively Monitor Adverse Events Associated with Drug Shortages

Utilize error and adverse event reporting systems as well as a hotline, chart review, focus group meetings, discussions during pharmacy rounds, or other means to learn about hazardous conditions, near misses, and adverse events associated with drug shortages so actions can be taken to limit further risk and harm.

As a final recommendation, healthcare organizations might want to share the results of our recent survey on drug shortages with pharmacy and therapeutics committee members and key groups of organizational leaders and clinicians, including nurses and the medical staff, to help illustrate the significant impact of drug shortages, particularly the types of adverse events that are happening across the nation. The full results of our survey can be found in our September 23, 2010, newsletter at:www.ismp.org/Newsletters/acutecare/articles/20100923.asp.

Abstract and Introduction

Abstract

High-fructose corn syrup is often mischaracterized and misunderstood. This sweetener was introduced into the food supply in the United States in the late 1960s as a liquid sweetener alternative to sucrose and existed in relative obscurity for many years. It carries the designations “Generally Recognized As Safe” (GRAS) and “natural” from the US Food and Drug Administration. In 2004, several investigators suggested that high-fructose corn syrup might be linked to the increased prevalence of obesity in the United States. Subsequent human studies have shown no unique link between high-fructose corn syrup and obesity. In composition, high-fructose corn syrup, sucrose, honey, invert sugar, and concentrated fruit juices are essentially interchangeable, and human studies to date have shown no significant differences in metabolic, endocrine, hormonal, or appetitive responses to these caloric sweeteners. This review explores the metabolic and nutritional effects of high-fructose corn syrup with a particular emphasis on its relationship to sucrose, the sweetener it replaced in many food products.

Introduction

High-fructose corn syrup is one of the most misunderstood food ingredients in all of nutrition. High-fructose corn syrup (HFCS) was first developed in the mid-1960s and, because of its unique physical and functional properties, was widely embraced by food formulators. The use of high-fructose corn syrup has had rapid growth over the past 30 years principally as a replacement for sucrose (table sugar). Its use reached a peak in 1999 but has been in decline since then. Having existed as a benign and noncontroversial product for more than 30 years, high-fructose corn syrup has recently been caught up in a series of controversies that started in 2004 when Bray et al^[1] suggested that there might be a link between high-fructose corn syrup consumption and obesity.

In their 2004 article published in the American Journal of Clinical Nutrition, Bray and colleagues^[1] argued that the dramatic increase in the prevalence of obesity in the United States over the past 30 years occurred during the same timeframe as a corresponding increase in the consumption of high-fructose corn syrup. Even though a temporal association does not establish cause and effect and high-fructose corn syrup and sucrose are virtually the same from a composition and biochemical point of view, a number of researchers began to investigate whether there was something unique about high-fructose corn syrup when compared to sucrose, which might create a unique hazard for obesity or other metabolic problems. This was particularly important because many of the hypotheses to date had been based on comparisons of pure fructose to pure glucose, which are not common in the food supply.^[2–4]

There is now abundant research demonstrating no short-term differences between high-fructose corn syrup and sucrose in any parameter yet measured in human beings.^[2,4–10] This includes work in both lean^[5,8–10] and obese^[6,7] individuals. In addition, the published proceedings from several different conferences that brought together leading researchers in the field of nutritive sweeteners have provided uniform scientific opinion that, from a metabolic standpoint, there is nothing unique linking high-fructose corn syrup to obesity or other metabolic problems when compared to other nutritive sweeteners, including sucrose, honey, and fruit juice concentrates.^{[3,8,11–15]} Both the American Medical Association,^[16] which explored whether there was a unique link between high-fructose corn syrup and obesity, and the American Dietetic Association have concluded that high-fructose corn syrup is not a unique cause of obesity.^[17]

The purpose of the current review is to provide practicing physicians and allied health care workers with a summary of the modern scientific understandings of high-fructose corn syrup, with particular emphasis on the comparison of high-fructose corn syrup to sucrose, the substance it was designed to replace in certain foods and beverages.

Discussion of the Scientific Evidence

We address issues related to high-fructose corn syrup by posing and answering a series of commonly asked questions about this sweetener. In our discussion, we draw on published research and published proceedings from 2 important, contemporary symposia on sweeteners.

What is High-fructose Corn Syrup?

High-fructose corn syrup is a liquid sweetener developed as a liquid alternative to sucrose (table sugar).[18] It is used in many foods and beverages to enhance flavors or sweetness. In baked goods, it enhances moisture retention and browning. Early developmental work on high-fructose corn syrup started in the 1960s, and commercial applications began in the late 1960s and early 1970s. Because of a variety of properties such as ease of handling (high-fructose corn syrup is supplied in liquid form rather than the solid form of sucrose) and other beneficial physical and functional properties, the use of high-fructose corn syrup achieved substantial growth over the next 30 years.

High-fructose corn syrup served industry in relative obscurity for many years. This is not surprising, given that it is virtually identical to sucrose: both consist of roughly equal amounts of glucose and fructose (see Table 1), have equal sweetness, have equal calories per gram, and are metabolized virtually identically. During this time, multiple expert scientific panels concluded that sucrose, high-fructose corn syrup, and their components, fructose and glucose, did not pose any significant health risk with the sole exception of promoting dental caries.[4,19–22] Added sugars have since been categorized as “discretionary calories,” and moderate intake is recommended.[17,23,24] The question addressed in this article is whether any one caloric sweetener, specifically high-fructose corn syrup, is metabolically or nutritionally unique.

Glucose, fructose, and sucrose from fruit or honey have been part of the human diet for millennia. Sucrose has been produced commercially from sugarcane and sugar beets for hundreds of years and continues to serve as the benchmark against which other sweeteners are measured. Worldwide, 9 times as much sucrose is consumed as high-fructose corn syrup. It would likely surprise many to learn that even in the United States, more sucrose is consumed per capita than high-fructose corn syrup.[15,23,25] The fact that obesity is as prevalent in countries that use little or no high-fructose corn syrup as in the United States substantially weakens the Bray hypothesis[1] of a unique link between high-fructose corn syrup and obesity.

High-fructose corn syrup proved to be an attractive alternative to sucrose because of its stability in acidic foods and beverages (eg, soft drinks). It is also an ingredient derived from corn, a dependable and renewable agricultural material grown abundantly in the midwestern region of the United States. In a sense, high-fructose corn syrup should be viewed as “corn sugar.” From this perspective, it could properly be viewed as a reasonable agricultural alternative to sugar (sucrose) produced from sugarcane and sugar beets.

How does the Composition of High-fructose Corn Syrup Compare with other Nutritive Sweeteners?

It is important to understand that essentially all nutritive sweeteners in common use in the American diet are similar combinations of glucose and fructose. Two main forms of high-fructose corn syrup are in common use. HFCS-55, which is composed of 55% fructose, 42% glucose, and 3% glucose polymers, is the form of high-fructose corn syrup commonly used in soft drinks. HFCS-42, consisting of 42% fructose, 53% glucose, and 5% glucose polymers, is the common form of high-fructose corn syrup used in baked goods.

Table 1 provides the carbohydrate composition of common nutritive sweeteners. As can be observed from the data in this table, HFCS-55 and HFCS-42 are very similar in composition to sucrose, invert sugar, and honey. From a practical standpoint, all 4 of these nutritive sweeteners are essentially interchangeable in many foods and beverages. High-fructose corn syrup and sucrose are both very different from “regular” corn syrup and pure fructose: corn syrup is glucose based with no fructose and low sweetness, whereas the latter contains no glucose and is used only in specialty applications. The name high-fructose corn syrup does not mean the fructose content is much higher than other sweeteners, but that name was given because its fructose content is higher than the corn syrup from which it was derived. These distinctions are particularly important because considerable confusion has risen in both the medical literature and lay literature, where improper references and comparisons between regular corn syrup, pure fructose, and high-fructose corn syrup are frequently made. The proper comparison is between high-fructose corn syrup and sucrose.

Is Consumption of High-fructose Corn Syrup Linked to Obesity?

As indicated earlier, Bray et al[1] suggested in 2004 that there might be a link between increased consumption of high-fructose corn syrup and dramatic increases in obesity in the United States. These authors subsequently acknowledged that their opinion piece was intended to be provocative and stir a scientific debate. Indeed it did. Multiple studies from a variety of research laboratories,[2,5–10] as well as proceedings from 2 major symposia on nutritive sweeteners[3,8,11–15] have all uniformly concluded that, based on current science, there is no unique association between high-fructose corn syrup and obesity. Furthermore, the American Medical Association studied this issue for over a year and concluded that high-fructose corn syrup “does not appear to contribute more to obesity than other caloric sweeteners.”[16] Finally, the American Dietetic Association[17] stated, “No persuasive evidence supports the claim that the high fructose corn syrup is a unique contributor to obesity.”

Perhaps the most succinct synopsis of this issue came from G. Harvey Anderson[26] in an editorial for the American Journal of Clinical Nutrition, where he wrote: The hypothesis that the replacement of sucrose by HFCS in beverages plays a positive role in obesity is not supported on the basis of its composition, biologic actions, or short-term effects on food intake. Had the hypothesis been phrased in the converse, namely that replacing HFCS with sucrose in beverages would be seen as a solution to the obesity epidemic, its merit would have been seen more clearly. Put simply, a proposal that a return to sucrose containing beverages would be a credible solution to the obesity epidemic would have been met with outright dismissal.

What are the Findings of Current Research on High-fructose Corn Syrup and Sucrose?

The original Bray hypothesis[1] received additional traction from research performed by Teff et al,[27] who employed a model in which individuals consumed 25% of calories either as pure fructose or pure glucose in the context of mixed-nutrient meals over 1 day. Individuals who consumed 25% of calories from glucose experienced a spike in blood glucose and insulin when compared to individuals who consumed 25% of calories from pure fructose. The reduction in meal-dependent insulin secretion in individuals who consumed 25% of calories from pure fructose resulted in suppressed circulating levels of leptin and less ghrelin suppression. It was argued on the basis of this experiment that consumption of fructose could lead to overconsumption of calories by attenuating insulin and leptin concentrations, as well as ghrelin suppression.[27] When these experiments were repeated using realworld diets comparing 25% of calories from high-fructose corn syrup to 25% of calories from sucrose in the context of mixed-nutrient meals over the course of a day, all of the differences in short-term energy regulating hormone levels disappeared.[5] The contrast between these 2 sets of experiments carried out with virtually identical research procedures but different sugar comparisons (pure glucose and pure fructose[27] [not commonly found in the diet] or high-fructose corn syrup and sucrose[5] [commonly found in the diet]) underscores the danger of extrapolating data from pure fructose and pure glucose into the real-world situation of high-fructose corn syrup and sucrose. In addition, in neither experiment did the participants express differences in appetite either during testing or the day after.

A comparison between high-fructose corn syrup and sucrose has also been made on appetite and caloric consumption at subsequent meals.[5] Recent research has shown no difference between high-fructose corn syrup and sucrose on appetite or caloric consumption at the next meal.[9,10]

It has also been argued that high-fructose corn syrup consumption may increase levels of uric acid.[28] If this were true, it would be cause for concern because there is a purported link between elevated levels of uric acid and some underlying components of the metabolic syndrome.[28] Evidence for a linkage between pure fructose consumption at high levels and increased uric acid levels comes from animal experiments performed by Johnson et al,[28] in which laboratory rats were fed more than 60% of calories from pure fructose. In this model, it was demonstrated that uric acid increases. However, research using high-fructose corn syrup and sucrose at 25% of calories (far above typical human consumption levels) over the course of 1 day did not show any differences or abnormal elevations in uric acid levels.[6]

It has been suggested that high levels of fructose consumption may also cause lipid abnormalities, particularly to postprandial elevations in triglycerides.[10] Once again, data supporting this assertion come from experiments that use high levels of pure fructose (typically 25% of calories). Recent experiments comparing mixed-nutrient meals with 25% of calories from either high-fructose corn syrup or sucrose in both lean and obese women again showed no shortterm differences in triglycerides, nor were there any significant elevations in postprandial triglycerides.[7]

A few animal studies have compared effects of high-fructose corn syrup and sucrose over longer terms and have raised questions about risks of obesity and metabolic syndrome with high-fructose corn syrup.[29] However, the doses used far exceed any that would be consumed by humans. Longer-term human research is currently under way comparing the effects of common sweeteners at typical intake levels in a broad range of test participants.

It must be recognized that most experimentation in support of a unique metabolic role for high-fructose corn syrup in obesity and related diseases relies on test diets featuring exaggerated amounts of pure fructose at levels never encountered in the human diet. Marriott et al[30] recently estimated mean and 95th percentile intakes at 9% and <18% of total calories, respectively. Experimental diets featuring 25% to 40% or 60+% of calories as fructose are commonly used in human and animal studies, respectively. Although exaggerated levels generate reportable differences between fructose and controls, they are not physiologically relevant to humans and should not be used to judge risk or guide public health decisions.

If High-fructose Corn Syrup is not Causing the Obesity Epidemic, What is?

Numerous studies, including those providing the basis for the Dietary Guidelines for Americans 2005 [24] and the Surgeon General’s report on obesity,[31] have provided compelling evidence that the obesity epidemic in the United States (and other industrialized countries) is multifactorial in origin and can be largely attributed to the significant increases in per capita calorie intake and decreases in physical activity, which have occurred in the United States and other industrialized countries over the past 30 years. As can be seen in Figure 1, average caloric consumption in the United States increased 25% between 1970 and 2005.[32] Couple this increase in caloric consumption with declines in levels of physical activity, and an environment is set up to promote weight gain. Today, added sugars account for approximately 17% of daily caloric intake. And although added sugar consumption increased during this period—along with all other macronutrients—it should be noted that as a percentage of total calories consumed, added sugars actually declined slightly, whereas added fats and flours/cereals modestly increased.[32] Thus, Americans are eating more of everything than in 1970, when high-fructose corn syrup was introduced to the food and beverage industry.[15]

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Figure 1.
Per capita daily caloric intake (US Department of Agriculture Economic Research Service loss-adjusted availability), 1970–2005.

What should the Lifestyle Physician and Practitioners Know about High-fructose Corn Syrup in Sports Drinks?

High-fructose corn syrup and other sweeteners are commonly found in sports performance drinks, where they have been proven to maintain glucose homeostasis and provide energy substrates to maintain or improve exercise performance over long durations. Of particular importance, it has been shown that consumption of the combination of glucose and fructose results in greater exogenous carbohydrate oxidation and better athletic performance than when either monosaccharide is consumed alone.[33,34] The added calories from high-fructose corn syrup or other carbohydrates in these settings are probably less important than the performance benefits that come from the addition of these carbohydrates.