INTRODUCTION

Fad diets have always existed but have been on the rise in recent years due to the explosion of social media in the 21^st Century. A fad diet is a popular diet followed to achieve fast results or fix long-term problems associated with eating, specifically weight.¹ Fad diets are labeled as fads for a reason. These short-lived trends with wide popularity disregard for the rationale behind or quality of the approach itself.^3,4

People who choose fad diets are often trying to fix ongoing problems including overweight or obesity, inadequate nutrition, sedentary behaviors, and failure to maintain overall healthy habits.² Individuals who follow fad diets adhere to a mainstream concept of dieting without acknowledging individual health needs and restrictions. Health consequences may arise as a result of adhering to a diet ill-suited to an individual's nutritional needs and ability to sustain the associated effort. In addition, certain diets may influence medication interactions and disease outcomes. For this reason, fad diets can undermine patient safety.

This continuing education activity summarizes popular fad diets to inform pharmacy teams of their benefits and risks. It will allow teams to make recommendations for patients, understand how medications interact with the diets, and help prevent health complications.

The History of Fad Diets

Fad diets have existed throughout history in different forms. For example, in the 1920s, the Cigarette Diet was popular. Lucky Strike, a cigarette company, promoted the cigarette diet. They claimed that cigarettes would suppress appetite to boost sales using the tagline “Reach for a Lucky instead of a sweet.” Promoters advertised that people would lose weight successfully while following the diet.⁶ The 1940s saw the rise of the Master Cleanse. This juice cleanse consisted of a meal replacement drink consisting of hot water, lemon juice, maple syrup, and cayenne pepper. Its popularity stemmed from promises of cleansing the body of toxins while providing very few calories. It reached new levels of popularity in 2006, when superstar Beyoncé claimed to lose 20 pounds in two weeks using this method ⁶ In the 1960s, The Drinking Man’s Diet made an appearance. The recommendation was to consume high-protein and low-carbohydrate foods while drinking as much alcohol as desired. An example meal may have included a large serving of steak, salad or vegetables, and several alcoholic beverages. The Drinking Man’s Diet’s supporters considered alcohol a good carbohydrate and allowed indulgence. This diet was marketed toward the male population.⁶

People have always been interested in quick fixes for weight loss and appearance without considering how they will feel or how to keep the weight off indefinitely.¹ This approach to choosing a diet or making nutrition decisions ignores tactics that sustain weight loss. Fad diets are inherently unsustainable options that often lead to weight regain. These outcomes prove many fad diets are unreliable (if not dangerous).

With the creation and explosion of modern social media in the early 2000s, fad diets surged in popularity. Social media often fosters a community of misinformation regarding fad diet composition, how to follow the specific diet, and the diet’s benefits.⁵ Much of the information on social media regarding fad diets lacks reputable, verifiable sources. Fad diet promoters use scientific jargon loosely and inappropriately to make information convincing when describing seemingly miraculous diets. However, the information could just be the opinion of an individual or a promotional company sponsorship.⁵ Unless diet information is published by a credible source, it should be regarded as untrustworthy.

Pause and Ponder: How many times a week do you see diet-related content on social media?

Fad Diet Prevalence

Approximately 45 million Americans (about 14% of the total population) go on a diet each year.⁷ Of these diets, 50% are fad diets.⁷ According to the United States (U.S.) Weight Loss & Diet Control Market, the weight loss industry is one of the most advertised with investors spending $66 billion annually.⁷ More people than ever are overweight or obese and using diets as a solution. Table 1 summarizes obesity’s prevalence, which is rising each year in the U.S.

Table 1. Obesity Prevalence in the U.S. Population⁸

According to the Centers for Disease Control and Prevention (CDC), individuals who are overweight or have obesity are at elevated risk for many health issues. These include elevated cholesterol, stroke, heart disease, hypertension, cancer, type 2 diabetes, mental illness, low quality of life, and mortality, among others.⁹ While many factors can influence weight, individuals can adapt their diets to meet nutritional needs and make long-term differences to improve health outcomes.

TYPES OF FAD DIETS

As the definition implies, fad diets’ popularity increases and decreases with current trends. This section discusses some of the most popular current fad diets.

Intermittent Fasting

Individuals following an intermittent fasting diet alternate eating and fasting (not eating or drinking anything) on a cyclic schedule. This diet focuses more on eating during specific periods of time than restricting meal components. Various intermittent fasting schedules exist, but popular versions include alternate-day and time-restricted fasting.^10,11 Alternate-day fasting means fasting every other day, while time-restricted fasting involves eating within set time windows during the day. Individuals should consult a doctor and choose the type of intermittent fasting that best fits their health needs (but most do not). Studies show following intermittent fasting schedules leads to decreased body weight, body mass index (BMI), and waist circumference.¹¹ Studies also show improved blood glucose and triglyceride levels following this diet.¹⁰

The body uses ingested calories—specifically carbohydrates, sugars, and nutrients—as fuel.¹⁰ If people eat continuously throughout the day, the body uses ingested calories as fuel to perform necessary bodily functions. The body stores unused ingested calories in the form of fat where they become an energy reserve.^10,12

When the period between meals lengthens and the body lacks a constant supply of calories for fuel, it turns to the fat reserve to burn fat stored in the body. The theory is that the longer a person goes without eating, the more the body will use its fuel reserve. The more reserve is used, the more fat is burned.¹⁰ As more of the reserve is used for energy while intermittent fasting, more weight is lost through fat burn.

Intermittent fasting regulates eating times without restricting foods or food groups. Dieters must make conscious choices to include foods beneficial to health. This includes fruits, vegetables, plant proteins or lean meats, whole grains, superfoods (see Sidebar: Superfoods), and low-fat dairy options.¹² Healthy choices also include limiting processed foods and sugars.

Sidebar: Superfoods¹³

Superfoods are nutrient-rich and high in important dietary components including antioxidants, vitamins, minerals, fiber, and healthy fats. These help keep the body functioning, reduce disease risk, and improve well-being. Some examples of superfoods are

• Avocados → These include potassium and healthy fats to lower the risk of heart disease.
• Chia seeds → These include fiber, protein, antioxidants, vitamins, and minerals. They are also easy to add to recipes.
• Dark and leafy greens → All greens are good greens, but these are especially nutrient dense, including vitamins A, C, and E. They also contain vitamin K, which promotes bone health.
• Ginger → This includes vitamin C, magnesium, and potassium. It also helps reduce pain and aid nausea.
• Salmon → Fish is high in omega-3 fatty acids, which can help reduce heart disease.
• Yogurt → This includes calcium and protein to help with bone health, cancer prevention, and immune health. It is also a good source of probiotics to support gut health.

Pause and Ponder: Do patients ask about superfoods when discussing dietary information or supplements? Do you know which to recommend?

Pros and Cons

Like most diets, intermittent fasting has benefits and drawbacks. Following intermittent fasting correctly boosts memory, improves blood pressure, induces fat loss while maintaining muscle mass, helps prevent obesity, improves type 2 diabetes by reducing insulin resistance, and improves tissue health.^12,14 Intermittent fasting also regulates the body’s 24-hour cycle to improve physiological functioning and metabolic health. As a result, gastrointestinal (GI) microbiomes, energy levels, and sleep may improve.¹⁵

Drawbacks of this diet include issues with long-term maintenance/adherence, leading to regaining weight.¹⁰ It is difficult and tiring for individuals to maintain fasting for extended periods. In addition, until the body is accustomed to fasting periods, symptoms such as headaches, nausea, or dizziness may occur. Some individuals may feel an initial decrease in energy levels when starting this diet.¹⁰

Keto Diet

The keto diet, also known as the ketogenic diet, is centered around depriving the body of carbohydrates.¹⁶ Researchers originally developed the ketogenic or keto diet in the 1920s as an epilepsy treatment, especially for resistant pediatric cases.¹⁷ The rise of effective antiepileptic drugs and treatments decreased use of the ketogenic diet for this purpose. As originally designed, total daily calories were composed of high fat intake (70% to 80%), moderate amounts of protein (10% to 20%), and low carbohydrate intake (5% to 10%).¹⁶ An iteration of this diet has gained more traction since the 1990s, as people realized its effectiveness for quick weight loss.¹⁶

The keto diet helps with weight loss through the processes of gluconeogenesis and ketogenesis. Under normal circumstances, carbohydrates produce energy for the body.¹⁶ When insufficient carbohydrates are available, insulin secretion is reduced and glucose is less available. The body then exploits gluconeogenesis, using lactic acid, glycerol, and amino acids to produce glucose as an energy source.¹⁶

If carbohydrate levels drop further, the body enters ketogenesis and secretes ketone bodies as an alternative energy source.¹⁶ As insulin secretion levels remain low and ketone bodies are used for energy, fat and glucose storage falls significantly. This can cause other fats to break down, leading to bodily fat loss.¹⁶

To remain in ketogenesis, the body needs constant carbohydrate deprivation.¹⁶ The longer it is deprived of carbohydrates, the more fat is burned in the ketotic state. This is known as nutritional ketosis and is considered safe, as opposed to the metabolic state of ketoacidosis (an accumulation of ketones that increases the blood’s acidity), which can be life-threatening.¹⁶

During ketoacidosis, ketone bodies are produced in large amounts and can acidify the blood pH.¹⁶ Acidic blood pH reduces the amount of oxygen blood delivers to cells leading to cell death and life-threatening complications. Insulin keeps the production of ketone bodies at bay, so sometimes people with type 1 diabetes develop ketoacidosis due to decreased insulin production. Taking diabetes-related medication correctly reduces the risk of ketoacidosis in people with diabetes. Following a low carbohydrate diet for a prolonged amount of time can also lead to ketoacidosis.¹⁷ To reiterate, ketogenesis is the production of ketone bodies in response to carbohydrate and glucose depletion. Low concentrations of ketone bodies are generally regarded as a safe, as opposed to high concentrations caused by ketoacidosis (which is a medical emergency).¹⁶

What to Eat and Avoid

Given the strong emphasis on high-fat foods, healthy fats comprise the largest part of this diet.¹⁶ Foods such as seeds and nuts, coconut, avocados, poultry fat, and plant fats (e.g., olive or coconut oils) are encouraged. In addition, some dairy products—including butter, hard cheese, and yogurt—are allowed, but people on a ketogenic diet should avoid cream, ice cream, and full-fat milk given their natural sugar content.¹⁷ Individuals following this diet should consume a moderate amount of protein, ideally meats high in omega-3 fats.¹⁶ This includes grass-fed beef, free-range poultry, wild-caught fish, and pork. Nuts, seeds, tofu, and eggs are also acceptable protein sources.¹⁷

Adhering to a diet with less than 10% of calories from carbohydrates can be challenging, especially since this diet requires individuals to calculate “net carbs” (See Sidebar: What are “Net Carbs”?).¹⁶ Vegetables lacking high starch contents (e.g., cauliflower, broccoli, onions, leafy greens, bell peppers, garlic, mushrooms, cucumber, summer squash) are encouraged. Small portions of fruit are also allowed, and fruits with a lower net carb content (e.g., berries) are preferred. Other acceptable carbohydrates include dark chocolate, herbs, spices, unsweetened tea, coffee, vinegars, and mustards.¹⁷

Sidebar: What are “Net Carbs”? ¹⁷

The body cannot digest or metabolize some carbohydrates because of their molecular structures. For example, fruits, vegetables, whole grains, and sugar alcohols contain insoluble fibers that are indigestible. Insoluble carbs have no energy value or blood sugar impact, so they are allowed when following the keto diet. The keto diet requires dieters to calculate “net carbs,” the amount of carbohydrates taken in by the body that are digested and metabolized and thus contribute to calories. However, it is important to note that the total calorie level does not change even when “net carbs” are calculated.

Individuals calculate net carbs by subtracting the number of ingestible carbohydrates from the food’s total amount of carbohydrates. For example, food containing 24 total carbohydrates and 21 ingestible carbohydrates equals 3 net carbs. Ingestible carbohydrates can typically be found by subtracting the amount of fiber from the amount of carbohydrates in the food item, but it can be more complicated. A number on online net carb calculators are available to help.

Net carbs are also known as “impact carbs.” Food manufacturers use both terms as marketing strategies, but governing bodies do not regulate use of these phrases.

Foods containing added sugar, whole or refined grains, and flour products are restricted.¹⁷ Starchy foods are also not allowed, including some high-starch vegetables such as corn, potatoes, and winter squash. Fruits with a high net carb content and fruit juices are restricted. Most keto programs also advise against alcoholic beverages due to their carbohydrate content and added sweeteners.¹⁷

Pros and Cons

The keto diet may be beneficial for weight loss, as it uses ketone bodies for energy to deplete glucose and fat storage abilities. Decreasing sugar intake lowers the risk of developing diabetes, obesity, and metabolic syndrome.¹⁶ Following this diet may reduce cholesterol, blood sugar, and blood pressure, and decrease insulin resistance.¹⁷

Diet restrictions may cause short-term adverse effects such as nausea and vomiting, fatigue, headaches, dizziness, and insomnia.¹⁶ This is known as the “keto flu.” Symptoms usually resolve once the body adjusts to the diet after a few weeks. Fluids and electrolyte replenishment can help alleviate discomfort during this period.¹⁶

Documented long-term adverse effects include increased uric acid levels in the blood, increased risk of kidney stones, and osteoporosis.¹⁷ This is due to the diet’s restrictive nature and omission of necessary components to sustain a healthy diet. Nutrient deficiencies can occur as a result of following this diet.¹⁷

People struggle to adhere to the ketogenic diet due to strict regulation of fat, protein, and carbohydrates.¹⁷ Dieters must carefully monitor their adherence to intake limits and meet target levels. This can be difficult for individuals to maintain long-term and lead to low adherence to the diet.¹⁷

Pay-for-Food Systems

Pay-for-food diets are meal prep services or meal delivery services with pre-portioned ingredients, pre-cooked meals, or meal replacement options. Diets focus on weight loss and are designed for convenience. These options take the guesswork out of planning meals and make it easier to track eating.

Nutrisystem

The Nutrisystem meal service claims its diets help with weight loss through a high-protein and low glycemic approach.¹⁸ Nutrisystem expects users to lose one to two pounds a week by managing blood sugar and controlling hunger to avoid overindulgence. Dietitians design meals to include healthy options and relieve the stress of planning.¹⁸

Meals are pre-portioned to fit an individual’s needs and tastes.¹⁸ The meals’ composition of lean protein, healthy fat, and smart carbohydrate ingredients is supposed to curb hunger. Protein shakes and bars are options to supplement plans. Nutrisystem claims deprivation is too restrictive and allows for some deviation from the plan or healthy alternatives to “bad foods.” In addition, dieters can track their progress and calories using Nutrisystem’s app. This system promotes prizes and special offers to keep individuals motivated.¹⁸

Prices vary by plan type but can range from $9.99 to $15.18 a day. Nutrisystem has plans designed specifically for men, women, partners, and people with diabetes.¹⁸

SlimFast

When SlimFast originated, the system promoted meal replacement shakes to lose weight.¹⁹ The company has since expanded to include drink mixes, snacks, and meal replacement bars. The products are grouped into categories such as calorie control, high protein, keto, and intermittent fasting. The website also contains a recipe section for dieters to use in their meal planning.¹⁹

SlimFast plans are based on individuals’ goals and preferences, including the Favorite Foods Plan, Keto Plan, High Protein/Low Carb Plan, Original Plan, and Intermittent Fasting.¹⁹ Dieters purchase SlimFast products to supplement or replace parts of their current diet. Plans themselves are not priced because individuals buy their own groceries and supplement with SlimFast products associated with the plan of their choice. The company also has an app to use for weight management tracking and a private Facebook group to communicate with other individuals on the diet to offer support or guidance.¹⁹ SlimFast claims their plans and products promote and maintain weight loss and encourage people to make better food choices.¹⁹

Jenny Craig

The Jenny Craig company has recently gone out of business after 40 years in the industry. Some experts indicates that one reason has been the availability of weight loss medications and increased competition in this market space. This system emphasized one-on-one coaching mixed with healthy foods to lose weight quickly.²⁰ The company claimed dieters could lose up to 18 pounds in the first four weeks. Coaches designed meal plans to be unrestrictive and included an individual’s favorite foods. Meals focused on low-fat foods with high fiber and protein. This program also emphasized physical activity and occasional intermittent fasting to aid the weight loss process.²⁰

Plans consisted of meals from the program, two snacks, and supplemental grocery items daily to promote weight loss and increase metabolism.²⁰ One snack included Jenny Craig’s Recharge Bar, used when intermittent fasting. The program claimed the Recharge Bar helped dieters lose weight faster, feel less hungry, and maintain fasting. Jenny Craig coaches designed plans and provided guidance for the duration of the program.²⁰

Food was delivered weekly or biweekly. Depending on the type of plan, individuals paid $13.99 to $21.99 per day. Prices were based on the number of meals, membership length, and amount of coaching support included. Promotional offers and meal bundles were available.²⁰

Pros and Cons

Pay-for-food diets can be intriguing as they promote healthy choices, weight loss, and convenience.^18-20  They reduce mental load and stress surrounding dieting by making the choices easier or eliminating the need to choose altogether. Some services also provide support groups or coaches for accountability and guidance. In addition, if dieters can adhere to these plans, meal kits promote portion control and reduce overeating.^18-20

A major con associated with these diets and meal kits is adherence. As people lose weight on these diets, they may stop using them, gain weight back, and become discouraged about trying again. This can reverse improved health outcomes.^18-20 Another con is cost. Individuals may be discouraged by the prices associated with pay-for-food systems. The cost may not be viable or sustainable options for all individuals.^18-20  

Studies have shown these diets to be ineffective. Attrition rates (percentages of people leaving a program) are 30% or greater, and 37% of dieters who complete programs lose less than 5% of their initial body weight.²¹ Other studies failed to produce significant results for how these pay-for-food diets affect weight loss when compared to educating or counseling individuals on weight.²² High attrition rates and insignificant weight loss results suggest these diets are unsustainable and unreliable.²¹

Paleo Diet

The paleo diet goes by many names, including the Paleolithic, caveman, or Stone-Age diet. It consists of (allegedly) eating like humans of the Paleolithic era did, mixed with modern components to supplement the diet. The Paleolithic era occurred from roughly 2.5 million years ago to 1,200 B.C. Diet supporters believe current body function is similar to how it functioned during this era and eating foods available or comparable to this time will improve health.²³ Introduced in 2002 by Dr. Loren Cordain, a scientist specializing in nutrition, this diet has surged in popularity in recent years due to weight loss claims.²⁴

Due to disagreements about which foods were available in the Paleolithic era compared with today, many diet plans are dubbed “paleo.” They differ in specific foods allowed. All plans emphasize high protein, healthy fats, low or moderate carbohydrates, low sugar and sodium, and high fiber to meet weight loss goals.²³ The term “paleo” will be used to describe this model. The paleo diet consists of consuming mostly lean meats, fruits, vegetables, nuts, seeds, and fish, in line with what researchers believe was consumed during the Paleolithic age.²³ It also emphasizes reducing intake of dairy, grains, and carbohydrates.²⁵

Weight loss can occur through several pathways using the paleo diet. ²³ Like the keto diet, ingesting fewer carbohydrates forces the body to use fat for fuel. In addition, replacing highly processed foods, added sugars, and large amounts of carbohydrates with healthier options can aid weight loss. Eating more protein and less calorically dense food (i.e., few calories in a large volume of food) also helps curb hunger and leave individuals more satisfied.²³

Less calorically dense foods—including vegetables, fruits, low-fat or fat-free dairy, and egg whites—can be eaten in larger quantities. These foods help with weight loss as they allow individuals to eat a larger volume and feel full, without ingesting large numbers of calories.²⁶ This reduces snacking and overall food intake.²³

Conversely, calorically dense foods are high in calories and eaten in small amounts. These contribute weight gain as individuals who eat a small volume consume high numbers of calories.²⁷ Examples of calorically dense foods include²⁷

• Proteins: fish, beans, eggs, cheese, yogurt, fats including nuts, avocados, nut butters
• Carbohydrates: potatoes, brown rice, whole grains

Overall, the paleo diet works by breaking down the diet into basic components and making healthier choices. Cutting out foods leading to high glucose or carbohydrate storage also aids in eating healthier and inducing weight loss.²⁸

What to Eat and Avoid

Allowed foods emphasize fresh and healthy choices to remain consistent with foods found in the Paleolithic age.²³ This includes lean meats, fish or shellfish, fruit, vegetables, honey, nuts or seeds, and olive or coconut oils. Frozen fruits and vegetables are allowed as they contain the same nutrients as the fresh variety and may be more convenient. Omega-3 fats are important for the body and can be found in fish, grass-fed beef, avocado, olive oil, some nuts (e.g., walnuts, almonds, pistachios), and seeds. Root vegetables such as cassava and sweet potatoes are highly nutritious and are allowed in moderation.²³

Restricted foods have little nutritional value or a high glycemic index unsuitable for the paleo diet.²³ For example, white potatoes and processed foods are off limits. Other restricted foods include whole or refined grains, cereals, refined sugar, refined vegetable oil, legumes, dairy products, alcohol, coffee, and salt. Canola is a refined vegetable oil and is not allowed. Restricted legumes include peanuts, beans, and lentils.²³

This diet emphasizes eating healthy and portioning fats, proteins, and carbohydrates to enhance health.²³ Calorie counting and general portion control are deemphasized in this diet. Some plans also allow for “cheat meals” (those consisting of food not beneficial to health) in the early stages of the diet to increase adherence.²³

Pros and Cons

Components of this diet including fiber, potassium, and antioxidants aid bodily functions and reduce disease risk. Reducing the intake of highly processed foods with little nutritional value also helps improve overall health.²⁵ Short-term benefits may include weight loss, improved blood pressure and cholesterol levels, and increased insulin sensitivity.²³ One study documented improvements in metabolic levels, specifically glucose control and lipids, in people with diabetes.²⁸

Unfortunately, restricting or excluding foods altogether for long periods of time can lead to nutritional deficiencies and health complications. For example, limiting dairy intake leads to deficiencies of calcium, vitamin D, and B vitamins.²³ These deficiencies can increase risk of osteoporosis and bone injuries.²⁴ Dairy-related nutrient deficiencies are not specific to the paleo diet, but can occur due to its food restrictions. Restricting grains in the diet also deprives the body of nutrients, which increases risks of diabetes and heart disease. In addition, increased meat consumption (especially red meat) contributes to saturated fat intake and increases risks of cardiovascular problems and diabetes.²³ It may also be difficult for people to adhere to a diet that restricts certain categories of foods.

Atkins Diet

The Atkins diet promotes low carbohydrate intake while allowing as much protein and fat as desired. Robert C. Atkins, a heart specialist, developed this diet in the 1960s as a method for weight loss and maintenance.³⁰ Although it is a low-carb diet, the Atkins program acknowledges that eating right is always better than eating less.³¹ This diet is ever evolving to be current with updated nutritional expertise.³⁰

Like the keto diet, Atkins emphasizes low carbohydrate intake of less than 20 g per day to start.³⁰ Unlike the keto diet, consumption of fat and protein is less restricted. Carbohydrates are claimed as the problem without regulating the intake of other food groups. Diet supporters believe the sugars found in carbohydrates cause health issues such as blood sugar imbalances and weight gain.³⁰

Hypothetically, eating fewer carbohydrates lowers dietary sugar leading to greater satiety, increased energy, less stored fat, and higher metabolism.³¹ When the body lacks glucose and carbohydrates to use as energy, it turns to fat to keep the body functioning through ketogenesis. The more fat a person burns, the more weight they lose.

Fat and protein comprise the remainder of the diet. As carbohydrates are viewed as the source of health issues, intake levels of fat and protein are less restricted. Calorie counting and portion control are unnecessary, besides keeping track of carbohydrate intake to stay below the allowable limit.³⁰

The Atkins diet is split into phases with specific allowable limits of carbohydrates (see Table 2). The diet’s phases adjust to reflect changes in body function and weight. As carbohydrate levels fluctuate in each phase, protein and fat levels change to achieve satiety.

Table 2. Atkins Diet Phases³¹

While phases differ in carbohydrate intake levels, they include similar food groups overall.³⁰ Allowed foods include vegetables, oils, fats, and protein (e.g., eggs, cheese, fish, meat and poultry). Dieters can introduce berries, nuts, seeds, starchy vegetables, and whole grains in the third phase, provided they are still losing weight. Dieters can also eat Atkins’ commercial selection of products during and after phase two. Most fruits, alcohol, baked goods high in sugar, bread, pasta, and nuts are restricted in phase one. Some fruits and grains are added by phase three.³⁰

Pros and Cons

Benefits of the Atkins diet include weight loss; decreased blood pressure; and lower incidence of heart disease, metabolic syndrome, and diabetes.³⁰ This diet can also improve blood sugar and cholesterol levels. These benefits are attributed to low carbohydrate intake and subsequent weight loss.³⁰

Reducing carbohydrate intake may initially cause symptoms such as headache, weakness, fatigue, and dizziness.³⁰ Unrestricted fat intake can be unhealthy. In addition, using fat as the body’s energy source for too long may lead to ketoacidosis if dieters misuse the plan.²⁹ Nutrient deficiency can also occur on this diet as a result of restrictions.³⁰

Weight loss pursuant to this diet is difficult to maintain due to its deficiencies and restrictive nature. Following the carbohydrate limit for long periods of time is difficult and unsustainable for some people.³⁰ Cardiologists warn this diet puts oxidative stress (disproportionate levels of oxygen reactive species overwhelming the ability of body systems to detoxify them) on organs and can cause serious heart problems or fatal complications.²⁹ Some long-term studies have shown the Atkins diet is no more effective than other fad diets. In addition, these studies show that most people who lost weight while following the Atkins diet regained it.³⁰

IMPLICATIONS FOR PHARMACY TEAM

Fad dieting can compromise patient safety, and certain patients are at elevated risk for problems. Pharmacy teams are responsible for advising patients about drug-diet interactions and concerns. Table 3 describes conditions and their associated medications that impact the use of fad diets.

Table 3. Implications for Pharmacy Teams^{10,16,23,30,32-40}

Nutritional Myths

As mentioned, misinformation surrounding diets has always existed, and social media has magnified the problem. Some myths are more harmful than others, but knowing the facts is essential to correctly informing others.³² Examples of nutritional myths that pharmacy teams can debunk for their patients are found in Figure 1.

Dieting is not a one-size-fits-all solution. When pharmacy teams advise patients, they must work with patients to consider health factors . Factors to consider include a patient’s medications, lifestyle choices, and known health issues.³³ Pharmacy teams should advise individuals that fad diets are not necessary and following a generally healthy diet is usually sufficient to lose weight. They should make healthy swaps and find strategies that work best for them as individuals. For example, they can cut back on processed foods, consume more fruits and vegetables, and be conscious of fat or carbohydrate intake to ensure healthy sources. These choices are effective ways to achieve the long-term goals without employing fad diets that promote quick fixes.³³

CONCLUSION

Fad diets are undeserving of the positive hype they receive. They are short-term solutions that sometimes work for people looking to lose weight or make changes quickly. However, benefits are outweighed by their unsustainability and poor post-diet maintenance planning. Fad dieting also starts a cycle of yoyo dieting (see Sidebar: Yoyo Dieting). The best option for health is to find strategies that work individually and stick with them. Ditch the fad diets and make long-term healthy choices for better, lasting results.³³

Sidebar: Yoyo Dieting

Yoyo dieting, or weight cycling, occurs when people achieve their goal weight through dieting, stop dieting and return to unhealthy habits, gain the weight back, diet again for a period, gain the weight back, and repeat the cycle. Yoyo dieting is not only a conscious choice. Physiological mechanisms related to energy intake and expenditure, genetics affecting weight control processes, and the interaction between genes and the environment also affect the cycle.³⁴

Yoyo dieting lacks substantial or sustainable changes to lifestyle or nutrition to keep weight off and instead focuses on quick fixes.³⁴ These quick fixes ultimately fail when weight is regained, and the cycle continues. Most weight lost is gained back within the first two to three years after dieting ceases. However, if dieters keep weight off for two years, the likelihood of gaining it back decreases.³⁵

Pause and Ponder: Do you think fad diets are helpful or harmful?

Resources for Pharmacists and Pharmacy Technicians

• CDC Resources - Healthy Weight, Nutrition, and Physical Activity ³⁶
  • https://www.cdc.gov/healthyweight/tools/index.html
• USDA - Healthy Living and Weight ³⁷
  • https://www.nutrition.gov/topics/healthy-living-and-weight

Download CE Activity

INTRODUCTION

Lifestyle modifications have been the mainstay of weight management for years. We’ve all heard the advice: Exercise more, eat less, limit fried foods and sugary drinks, and the weight should slowly disappear. As the weight comes off, you might have some setbacks but just keep tracking your foods and your success is right around the corner.

If only it was that easy!

Scroll any social media platform today and search the term, “#ozempicweightloss” and a plethora of joyful testimonials appear. Some videos have reports of people losing 17 pounds in 3 months or 64 pounds in a year with no cravings for food. “I can eat whatever I want!!” cried a satisfied user. It is as if the golden ticket has been found in all the candy bars ever produced and everyone is going to the candy factory!

Although the recent media emphasis has been on semaglutide, and the Ozempic product primarily, other glucagon-like peptide-1 (GLP-1) receptor agonists have also been associated with weight loss to varying degrees. This continuing education activity’s primary focus is to clarify misinformation, highlight specific GLP-1s’ risks and benefits when used for weight loss, and answer frequently asked questions.

WHAT ARE GLP-1 RECEPTOR AGONISTS?

Major breakthroughs in the physiology of the pancreas occurred in the early 1900s.¹ At that time, physiologists thought the nervous system had exclusive control of all bodily functions. That idea changed when two scientists, William Bayliss and Ernest Starling, discovered a chemical compound they named secretin. Released from intestinal mucosa, secretin stimulated the pancreas.² Shortly after the discovery of the hormone insulin in 1921, research being conducted at the time primarily stimulated the pancreas to produce insulin by administering glucose via the intravenous route. However, when glucose was administered orally (allowing nutrients to travel to gastrointestinal areas), insulin levels improved substantially. This observation was known as the incretin effect. As a result, two insulinotropic hormones were later identified as incretin hormones, glucose-dependent insulinotropic polypeptide (GIP) discovered in 1971 and glucagon-like peptide-1 (GLP-1) discovered in 1985.^1,2

Analyzing the venom of the Gila monster (Heloderma suspectum) in 1990, endocrinologist Dr. John Eng discovered a peptide that stimulated insulin release from the pancreas.³ Named exendin-4, this peptide was similar in structure and function to GLP-1 found in humans. One problem with GLP-1 was that when it is released into the body, dipeptidyl peptidase-4 (DPP-4). quickly inactivated it. Researchers then developed the DPP-4 inhibitors to allow GLP-1 to remain active for a longer period of time. However, synthetically producing GLP-1 receptor agonists (GLP-1RA) directly has extended the peptide’s life. Initial development resulted in twice daily and then daily administration (half-life of 13 hours) of GLP-1RAs. However, when researchers combined semaglutide with a free fatty acid side chain that was tightly bound to albumin, its half-life was increased substantially. The resultant half-life of 165 hours led to an advantageous injection administration schedule for semaglutide: once weekly.^3,4,5

Mechanism of Action

As a class of medications, all GLP-1RAs share common mechanisms of action in the treatment of diabetes: stimulate the pancreas to secrete insulin, suppress the action of glucagon, and decrease gastric emptying.⁴ Scientists previously studied the effects of GLP-1 and noticed that the protein, when injected in rats, decreased appetite quickly.⁵ Once clinicians began using GLP-1RAs to treat diabetes in humans, they also observed weight loss due to decreased appetite, increased feelings of fullness, and reduced caloric consumption.⁴

Researchers determined that the brain contained GLP-1 receptors. Weight loss was due to GLP-1RAs ability to travel to these receptors and influence specific areas of the hypothalamus that are key to controlling appetite, calorie consumption, satiety, and body weight.⁴ Among GLP-1RAs, semaglutide and liraglutide stimulate the highest amount of weight loss success.

Comparison of GLP-1 drugs

Table 1. GLP-1RAs for Weight Loss

Adverse Drug Reactions and Boxed Warning

GLP-1 agonists all have similar and common gastrointestinal adverse effects (nausea [~15–30%], vomiting [~10-15%], diarrhea [~5-10%], abdominal pain, constipation).^6,7,8 Patients can use some strategies to possibly mitigate these adverse effects^6,7,8:

• Increasing the GLP-1 agonist dose slowly
• Staying hydrated and increasing fiber
• Avoiding high-fat foods and alcohol
• Stopping eating when full (and eating only when hungry)
• Spacing meals appropriately
• Using short-term proton pump inhibitors or H₂ blockers if needed

Patients may also experience headache, fatigue, dyspepsia (gastrointestinal upset), dizziness, abdominal distension, eructation  (burping), hypoglycemia in patients with type 2 diabetes, flatulence, gastroenteritis, and gastroesophageal reflux disease.⁷ Clinicians should evaluate patients for gallbladder disease if cholelithiasis (gallstones) or cholecystitis (an inflamed gall bladder) is suspected.

Reports of patients experiencing hair loss have surfaced recently from news and social media. Listed as an adverse reaction for Wegovy, but not for Ozempic, the Wegovy dose is much higher for treatment of weight loss.⁹ Some clinicians think that the rapid loss of weight triggers the body to conserve calories consumed for essential functions.⁹ Since patients eat less while taking the medications, their diet may consist of lower amounts of protein and minerals important for hair growth. Clinicians have seen hair growth resume once the body reaches a plateau in weight loss, therefore the loss of hair is not permanent.⁹

These drugs also share a boxed warning for risks of pancreatitis and medullary thyroid carcinoma (cancer in the thyroid gland in its medulla, the calcitonin-producing area), which is rare.⁶ Patients with a personal history of pancreatitis or a personal or family history of medullary thyroid carcinoma must avoid these drugs.⁶

These drugs also required an FDA approved Medication Guide whenever GLP-1RAs are dispensed. Pharmacy technicians can be very helpful to pharmacists if they check the patient’s bag and make sure that the Medication Guide is in it.

Recent Shortages of GLP-1 Receptor Agonists

The sensation of weight loss success for some has caused serious problems for other patients who have diabetes and are struggling to find medication at local pharmacies. Staff in community-based pharmacy practice are well aware of the semaglutide shortages that have occurred in the past year. Pharmacists and technicians should be able to explain the current drug shortages, adverse reactions, and FDA approved or off-label use to patients and other healthcare providers.

“Ozempic face”

As social media and now news media have reported the success of dramatic weight loss, some users bemoan weight loss woes associated with use of GLP-1 agonists. The term, “Ozempic face,” introduced by a dermatologist in New York, describes the typical female patient who has lost a significant amount of weight on semaglutide but now needs (or wants) dermal fillers for her sagging facial structures.¹⁰ Patients complain about sagging skin and a gaunt appearance, two problems that follow the loss of facial fat after any harsh weight loss.

Facial fat loss is common when patients lose weight, and when the weight loss is significant, patients will look older. Skin wrinkles and loosens—hallmarks of aging. Similar to weight loss from old-fashioned dieting, fat loss while taking GLP-1 agonists affects the entire body (not just the face). But patients on GLP-1 agonists for cosmetic weight loss fail to understand that they can’t just lose weight where they’d like to lose weight. The facial fat loss is distressing to them.¹⁰ Pharmacy teams need to know that “Ozempic face” is a slang term, and GLP-1 agonists don’t specifically target the face.¹¹

Weight Loss Blockbuster or Fad

Over the past two years, celebrities and social media influencers have posted successful weight loss stories while using semaglutide and as a result, catapulted its popularity as a weight loss miracle.¹² Questions remain as to how long the weight loss effect will last and if patients will gain the weight back once stopping the treatment. Novo Nordisk, semaglutide’s manufacturer, indicates weight loss can be sustained with long-term use. However, the data collected is limited by a time span of two to three years. Since people who pay out-of-pocket for semaglutide will pay around $1200 per month and some insurance companies may not cover the medication, pharmacists should counsel patients that once the medication is discontinued, weight gain is likely to occur and the weight gain might exceed the original amount lost.¹²

FDA APPROVED AND OFF-LABEL USE

In December of 2017, the FDA approved semaglutide (Ozempic) for the treatment of diabetes. As significant weight loss was observed, the Semaglutide Treatment Effect in People with obesity (STEP) studies produced promising weight loss data.¹³ As a result, the FDA approved semaglutide for an additional indication, weight loss, in June 2021 under the brand name Wegovy.

Diabetes

In patients with type 2 diabetes mellitus (T2DM), semaglutide is used in combination with diet and exercise to reduce blood sugar levels.¹⁴ In patients with T2DM who additionally have established cardiovascular disease, liraglutide and semaglutide are indicated to help lessen the risk of major cardiovascular incidents. Dulaglutide, liraglutide, and semaglutide also have beneficial effects on chronic and diabetic kidney disease.⁶ Patients who have a history of pancreatitis should avoid any member of the GLP-1RA class and they are not to be used as treatment for patients who have type 1 diabetes.

Dosing semaglutide for the treatment of diabetes requires a period of time for dosage escalation to minimize adverse effects. The FDA has approved both subcutaneous and oral semaglutide (Rybelsus) dosage forms, but only the injectable version is approved for weight loss. Subcutaneously, semaglutide is initially dosed at 0.25 mg once weekly, and after four weeks the patient should increase to 0.5 mg weekly for four weeks. Doses of 1 mg and 2 mg are optional if glycemic control has not been achieved, however the 1 mg dose should also be used for a minimum of four weeks before increasing to the maximum 2 mg strength.⁶ Dosed on the same day of the week, injections can be dosed at any time of the day with or without regard to meals. Patients sometimes miss or forget their scheduled dosing day. If this occurs, patients should inject the dose within 5 days of the missed dose.⁶

Patients who have diabetes and currently use metformin, sulfonylureas, thiazolidinediones, or insulin can use semaglutide in combination.  However, patients can administer semaglutide and insulin injections at the same time and in the same areas of the body, but not close together; they must never mix them together in the same syringe.¹⁴ Hypoglycemic episodes are possible when using a sulfonylurea and/or insulin with semaglutide. Pharmacists therefore should remind patients of the signs and symptoms of hypoglycemia when these drugs are used together. Prescribers may need to adjust the dose of insulin and/or a sulfonylurea when starting semaglutide.⁶

Obesity and Weight Management

Affecting 70% of American adults, obesity and being overweight contribute to a variety of complications and have reduced quality of life.¹⁵ Debilitating and expensive disease states associated with obesity include: T2DM, cardiovascular disease, osteoarthritis, sleep apnea and cancer.^13,15 Since obesity has roughly tripled worldwide from 1975 to 2016, investigating the reasons for the rise in prevalence and finding solutions is of utmost importance to prevent and treat obesity.¹⁶

The access and ease of inexpensive prepared high caloric foods, limited physical activity, and sedentary life styles are factors that have contributed to the rise of obesity.¹⁷ As mentioned, treatment typically has concentrated around the modification of these lifestyle habits.¹⁸ Although the weight reduction is usually moderate in magnitude, it is recovered over time (yes, that means that people gain the weight back!).¹³

Anti-obesity medications have been added to lifestyle modifications. Discouraged by adverse drug reactions, contraindications, cost, and moderate weight loss results with weight that is regained over time, many patients and prescribers are hesitant to consider these treatment options.¹⁶

Maintaining weight loss has proved equally difficult due to the regulatory centers in the brain that control appetite. Increased hunger and abnormal satiety signals controlled by neuroendocrine pathways have been discovered in the hypothalamus.¹⁶ Researchers have also identified levels of hormones that regulate weight in the hypothalamus. These hormones (leptin, ghrelin, peptide YY, and GIP) play a role in counteracting weight loss after dieting and lead to regain of weight.^{17, 16}

Once semaglutide was approved for the treatment of diabetes, clinical trials focused on weight loss. The STEP trials were phase 3 studies implemented to evaluate the safety and efficacy of semaglutide 2.4 mg subcutaneously once weekly injections for 68 weeks. Patients enrolled in the studies were adults with obesity or overweight, a mean age of 46.2 to 55.3 years, mean BMI of 35.7 to 38.5 kg/m², and were mostly female (mean: 74.1% to 81.0%) for five of the trials.¹³All studies included lifestyle interventions at varied intensities.^{13, 18} In one of the larger studies that compared semaglutide with placebo, semaglutide was associated with a 12.4% loss of body weight.¹⁵As a result of the  ≥ 5% in weight loss exhibited in the studies, the FDA approved semaglutide for chronic weight management.^18,15 The approval came in June of 2021, and the manufacturer marketed semaglutide as Wegovy.

The STEP 8 trial compared once-weekly semaglutide to once-daily liraglutide and enrolled 338 adult patients with 126 receiving semaglutide 2.4 mg, and 127 participants receiving liraglutide 3 mg. Participants were overweight or obese, without diabetes, had a mean BMI of 37.5, and most had 0-2 comorbidities with dyslipidemia and hypertension being the most frequent.^{19, 18} The primary results at 68 weeks reported an estimated mean change in body weight at -15.8% with semaglutide, and -6.8% with liraglutide.¹⁹ Based on data from this STEP study, the researchers concluded semaglutide is far superior to liraglutide when used for weight loss and had significantly improved cardiometabolic risk factors.^{19, 18}

The most frequent adverse side effects reported in the STEP studies were gastrointestinal disorders. Most gastrointestinal side effects were considered mild or moderate in severity and usually were most prominent during the dose titration phase.¹⁹ In the STEP 8 study, semaglutide (84.1%) reported a higher occurrence of gastrointestinal events than liraglutide (82.7%).¹⁹  Other side effects reported were hypoglycemia, acute pancreatitis, gallbladder disorders that generally resulted in cholelithiasis (gall stones), malignant neoplasms (cancer), change in pulse and injection site reactions.^{18, 19}

SIDEBAR: Alcohol use disorder potential

As patient use of semaglutide has expanded over the past several years, a side effect has emerged that is surprising many clinicians. Patients have reported an abrupt loss in the desire to drink alcohol, almost to the point of repulsion for some patients. GLP-1RAs are known to decrease the desire, enjoyment, and consumption of fatty foods in humans, but observations that patients began to decrease alcohol consumption was unexpected. Although studies to date have observed a reduction of alcohol in rats, mice, and monkeys when receiving GLP-1RAs, reliable researchers avoid extrapolating results from animal studies directly to humans, especially since humans tend to consume more alcohol than animals.²⁰ Since several patients have reported decreased intake of alcohol and data from animal models reflect these results, researchers are starting to investigate GLP-1RAs effect on patients who have alcohol use disorder (AUD).

Existing studies on GLP-1RAs effect on AUD in humans are minimal. A recent study published from Denmark compared the use of a different GLP-1RA, exenatide 2 mg versus placebo in patients with AUD. Researchers were looking to determine if exenatide reduced the amount of heavy drinking days. At the same time, functional MRI brain scans were also completed during the study that focused on areas involved in addiction and reward centers of the brain. Administered once weekly to 127 patients along with cognitive behavior therapy for 26 weeks, exenatide failed to show a decrease in heavy drinking days.²¹  However, in a subgroup of obese patients (BMI > 30 kg/m²) heavy drinking days and total alcohol intake was reduced.²¹ Brain scans revealed weakened alcohol cue reactivity and lower dopamine transporter availability for those patients in the exenatide group.²¹

Ongoing phase two clinical trials are studying the effects of semaglutide on patients with AUD.²² Since semaglutide usage and availability have increased with approved indications for diabetes and obesity, researchers are continuing to investigate this drug class for potential promising new therapies.

Product information

When used for chronic weight management, semaglutide (Wegovy) is approved in addition to a reduced calorie diet and increased physical activity.^{7, 15} Semaglutide is indicated for patients who meet one of the following criteria: BMI of 30 kg/m² or greater, or patients who have a BMI of 27 kg/m² with at least one comorbid weight related condition (cancer, cardiac disease, diabetes, dyslipidemia, obstructive sleep apnea).^{7, 15} Available in a prefilled pen that contains one dose, semaglutide is a clear and colorless liquid that can be injected into the upper arm, lower stomach or upper thigh.⁷ Semaglutide should be stored in the refrigerator between 36°F to 46°F (2°C to 8°C).⁷ If the pen has been frozen, exposed to light, or heat above 86°F (30°C), the pen should be discarded. The pen remains stable and active for 28 days once removed from refrigeration. Each pen contains the exact dose to be delivered with the needle located inside each pen, therefore each pen should be disposed of in a sharps container.⁷

Drug shortages, alternatives for therapy

Shortly after marketing Wegovy, the facility hired by Novo Nordisk to fill syringes was cited by the FDA for issues with current good manufacturing processes.^{23, 24} As a result, deliveries and manufacturing of Wegovy was halted in December of 2021.²⁴ At the same time, staggering demand for the drug was reported by the manufacturer mainly due to news and social media platforms announcing the success of several celebrity weight loss stories. As a result of the Wegovy shortage, prescribers started to write for Ozempic off label in an effort to treat obesity and therefore depleted the supplies of Ozempic.²⁴ At the end of 2022 and early 2023, Novo Nordisk announced that supply issue resolution for Wegovy was on the horizon and that production of the drug was being increased. Due to residual and increasing demand though, some supply issues might continue sporadically but over time distribution centers and pharmacies should receive more drug product in the months ahead.²⁵

CONCLUSION

Probably the first drug to be considered a social media sensation, semaglutide’s entrance into the realm of prescription weight loss treatments has been filled with anticipation, fame, demand, intrigue, and acceptance. Lifestyle management will continue to play a role in losing and maintaining weight loss, with or without a GLP-1RA used in treatment for weight management. Long term use of semaglutide seems to be necessary to maintain a healthy weight but more research is necessary. Gastrointestinal side effects are seen as the most prevalent adverse effect, leading some patients to discontinue the drug. As availability of semaglutide increases due to resolution of the issues that halted production, price, and lack of coverage by insurance plans continues to be problematic for some patients. This is an area where pharmacy technicians can help by looking for coupons or patient assistance programs.

Researchers continue to investigate the various effects seen as a result of usage of semaglutide. Investigators are hopeful of finding new treatments for patients that are struggling with alcohol use disorder and addictive behaviors. GLP-1RAs will continue to be in the headlines for years to come. Pharmacists and technicians hold the golden ticket of information by helping patients and providers understand this unique class of medication’s history, mechanism of action, dosing, side effects, storage requirements, pricing and potential treatments being investigated.

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Introduction

Consuming natural substances to produce a desired effect on the body dates back thousands of years to ancient Egypt, Rome, China, and many other cultures. Records from early Mesopotamia include written formulas using many oils still in use today, including cedar, cypress, and licorice. Around 300 B.C., the Greek philosopher Theophrastus described the medicinal benefits of natural substances in his History of Plants. Throughout the centuries, many philosophers, scientists, and physicians continued collecting, combining, and documenting the use of natural products to treat different illnesses.¹

As the science of medicine developed, so did the science of pharmacology. Isolation of the active ingredients found in herbal substances lead to the development of synthetic compounds with similar properties. The first synthetic medication, chloral hydrate, derived from chloroform and discovered in the 1800s by German chemist Justus von Lieberg, is still in use today.²

Fast forward to modern day, and the interest and use of prescription medications, over-the-counter (OTC) products, and dietary supplements are at an all-time high. In 2020, consumers filled 6.3 billion prescriptions in the United States³ (U.S.) and purchased more than 6 billion OTC products.⁴ The dietary supplement market reached an unprecedented level in 2020 with a global spend of $61.2 billion. Experts predict it will reach $128.64 billion by 2028.⁵

The COVID-19 pandemic, caused by the SARS-CoV-2 acute respiratory coronavirus, significantly impacted our perception and approach to healthcare.⁶ More and more people use complementary and alternative approaches to healthcare than ever before.⁷ For example, sales of elderberry supplements more than doubled and zinc products quadrupled shortly after the pandemic's start.⁸

Pharmacists, widely recognized as drug information experts, and pharmacy technicians routinely field consumers' questions about dietary supplements. Many pharmacists lack the necessary knowledge or don't know where to look to answer these questions. Pharmacy schools educate future pharmacists on prescription and OTC medications with courses about nutrition and dietary supplementation, if offered, available as electives. This continuing education activity presents information about dietary supplements through a series of seven common pharmacy situations and lets learners in on seven secrets they can apply to their practices.

Situation: Continuing education is a professional requirement many pharmacists find tedious. Looking through the UCONN online CE library and seeing a new continuing education activity entitled ‘Seven Secrets of Patient Safety with Dietary Supplements,’ a pharmacist remarks to the pharmacy team, "What a waste, no one even takes dietary supplements."

Secret #1: Almost 60% of people in the United States used a dietary supplement in the last 30 days.^11,12

Dietary supplements crowd the aisles in drug stores, supermarkets, warehouse clubs, and even corner convenience stores. The sheer number of products is staggering. The Dietary Supplement Database (DSLD) is an online, searchable database developed by the Office of Dietary Supplements (ODS) at the National Institutes of Health (NIH). The database contains product labeling information on dietary supplements sold in the United States, including both on and off-market products. DSLD currently lists more than 140,000 labels.⁹

In the early 1960s, the National Center for Health Statistics began a program named the National Health and Nutrition Examination Survey (NHANES). NHANES is a continuous program focusing on various health and nutritional measurements and assesses adults' and children's health and nutritional status in the U.S.¹⁰ Scientific and technical journals publish the study results.

One section of the program assesses dietary supplement use among adults. Results from the 2017-2018 NHANES show that^11,12

• 57.6% of adults 20 years or older used a dietary supplement in the past 30 days
• Women (63.8%) had a higher utilization than men (50.8%)
• Use of dietary supplements increased with age, with women 60 years or older reporting the highest usage at 80.2%
• Use of multiple dietary supplements increased with age
• Most common dietary supplements used by all age groups include multivitamin-mineral supplements, vitamin D, and omega-3 fatty acids

The Council for Responsible Nutrition (CRN) is a trade association for the dietary supplement and functional food industry. Annually, the CRN performs a survey gathering data on consumer use of dietary supplements. The 2019 survey conducted by the CRN underscored dietary supplement usage with the following results¹³:

• 77% of US adults take dietary supplements, including 79% of American women and 74% of males
• Top reasons for taking supplements included:
  • Energy
  • Immune health
  • Filling nutrient gaps
  • Healthy aging
  • Heart health

The COVID-19 pandemic significantly impacted our perception and approach to healthcare.⁶ As of August 5, 2022, SARS-CoV-2 has infected more than 580 million people worldwide.¹⁴ Interest in boosting our overall immunity and protecting ourselves from viral infections has dramatically increased as a result.⁷ Many vitamins and minerals play essential roles in proper immune function.^7,15 Sales of supplements associated with boosting immunity increased over the last two years, including vitamins C and D, zinc, omega-3, garlic, ginger, and turmeric.¹⁶

Table 1. Common Dietary Supplements and Potential Uses^7,17,18

Eating a healthy diet is essential for good health and nutrition. The Dietary Guidelines for Americans advise professionals, including policymakers, health care providers, and nutrition educators, about what to eat to meet the body’s nutritional needs. It emphasizes eating a diet rich in nutrient-dense foods, such as fruits and vegetables, as the best way to meet the body’s nutritional needs. The guideline identifies specific populations in which dietary supplementation may be necessary, such as women who are pregnant or lactating and adults older than 50.¹⁹

In addition to these defined special populations, many pharmacy patients may find it necessary to take specific vitamins or minerals due to medication-induced nutrient deficiencies.

Table 2. Examples of Nutrient Depletion Induced by Medications^7,17

The pharmacist's dismissal of dietary supplement education is understandable. No one wants to waste precious time on irrelevant continuing education. However, the facts presented here illustrate the need for pharmacist education on dietary supplements.

Pause and ponder: A patient presents information about taking lemon and baking soda tea to prevent COVID-19 infection and asks you if it really works. How would you approach this conversation?

Situation: Sunday afternoons sometimes (but not often!) present the opportunity to catch up on administrative activities. While completing an inventory reconciliation of the vitamin section, a technician inquires, "Why does the FDA approve so many different products?" Looking up distractedly from the CII safe count, the pharmacist pauses, then replies in a weary voice, "You know, I’m not sure, probably just to make it more confusing for us."

Secret #2: Regulatory oversight of dietary supplements differs from prescription and OTC medications.

What is a Dietary Supplement?

On the most basic level, a dietary supplement is a substance consumed to add nutrients to a diet or to lower the risk of certain health problems. The use of natural substances has been around for millennia, but it is only within the last five decades that countries worldwide have formalized language and regulations around dietary supplements. Terminology, quality control, and safety assessment differ depending on the country and governing legislative body.²⁰

In 1994, the United States Congress passed the Dietary Supplement Health and Education Act (DSHEA), an amendment to the Food, Drug, and Cosmetic Act. DSHEA defines the term dietary supplement as a product intended for ingestion and containing an ingredient that supplements the diet. Dietary supplement labeling must include the term ‘dietary supplement’ or an equivalent term such as ‘herbal supplement’ or ‘magnesium supplement.’ DSHEA also stipulates that a dietary supplement must be free of contamination, adulteration, and properly labeled.²¹ We will discuss dietary supplement product integrity and labeling later in this activity.

According to DSHEA, dietary supplements include vitamins, minerals, herbs, other botanicals, amino acids, and live microbials (probiotics). Dietary supplements are available in many different formulations including tablets, capsules, soft gels, gel caps, powders, and liquids.²¹

DSHEA defined the term ‘new dietary ingredient’ as an ingredient that meets the above criteria and was unavailable in the U.S. before October 15, 1994. If manufacturers want to market a product containing a new dietary ingredient, they must notify the U.S. Food and Drug Administration (FDA) before marketing. The FDA then reviews the product for safety but not effectiveness.²¹

Regulation of Dietary Supplements

The FDA and the Federal Trade Commission (FTC) share regulation and oversight of dietary supplements. The FDA is responsible for the information provided on dietary supplement product labeling, including the package labeling, product inserts, and information available at the point of sale. The FTC monitors dietary supplement advertising, ensuring advertisements are truthful, substantiated, and not misleading. Both agencies have the authority to address violations and work together to ensure their efforts are consistent with one another.²²

The FDA does not have the authority to approve dietary supplement products before manufacturers market, distribute, and sell them to consumers. Manufacturers are responsible for ensuring the products they produce and distribute meet all quality standards defined by federal law. Quality standards include²²

• Ensuring the safety of the dietary ingredients used in the product
• Following current Good Manufacturing Practices (cGMP)
• Meeting all product labeling requirements
• Ensuring substantiation of all claims made about the product
• Ensuring products are free of adulteration or misbranding

cGMP, defined and regularly updated by the FDA, establish the minimum requirements for manufacturing, packaging, and labeling products to ensure product quality. cGMP includes guidance on obtaining quality ingredients, operating procedures, and quality controls.²³ Failure to follow cGMP results in possible product contamination.

While the FDA may not have the authority to approve dietary supplements before the product marketing and distribution, it can monitor products via post-marketing surveillance and auditing. The FDA routinely performs manufacturer inspections, monitors the marketplace, and investigates adverse event reports. Follow-up includes working with the manufacturer to bring the product into compliance, issuing warning letters, and recalling products.²¹

Reporting Issues with Dietary Supplements

Post-marketing surveillance is essential for documenting and monitoring any issues with dietary supplements. Information about severe reactions and product quality are important issues to report. The FDA Safety Reporting Portal is an online tool used to report safety issues on several categories of products, including pet or livestock foods, tobacco products, animal drugs, and dietary supplements.²⁴

The website address for the portal is https://safetyreporting.hhs.gov. Anyone can use the portal to report issues, including consumers, healthcare professionals, manufacturers, and researchers. Generating a new report starts on the home screen. The reporter chooses to file the report as a guest or by creating an account. Creating an account streamlines data entry and allows the reporting individual to save a draft of the report, follow up on a report, and view previous submissions.²⁴

Generation of an Individual Case Safety Report ID (ICSR) occurs after report submission. The ICSR allows the reporter to identify the report for future reference including submission of a follow-up report with additional information. FDA reviewers assess the seriousness of the reported issue and assign follow-up. Submission of this information allows the FDA to identify potentially dangerous products and potentially remove them from the market.²⁴

Traditionally, insurance companies limit coverage to prescription medications. Recent trends show an expansion of coverage to include some dietary supplements. Insurance coverage of dietary supplements blurs the regulatory differences between prescription medications and dietary supplements. Understanding the differences in oversight is beneficial and allows the pharmacy staff to counsel patients effectively.

Situation: While running back to the pharmacy after a much-needed bathroom break, a pharmacist stops when approached by a customer asking for advice about an iron supplement. Overhearing the inquiry, another customer comments, "You should buy that online; it’s cheaper, and the quality is just as good." The pharmacist nods assent, turns, and hurries back to the pharmacy amid the erupting sounds of chaos behind the counter.

Secret #3: Product integrity fluctuates between manufacturers and sources of dietary supplements.

Integrity of Dietary Supplements

The lack of government oversight opens the door for substandard products to flood the market. Poor ingredient quality, heavy metal or microbial contamination, adulteration, and mislabeling occur regularly. In the current economy, with rising prices, consumers are turning to less expensive options, and cheaper is not necessarily better, especially with dietary supplements.

In the literature, many studies exist that analyze dietary supplement product integrity. A study published in 2021 tested multiple bottles of 29 herbal supplements for consistency of ingredient activity and the presence of metal and fungal contaminants. The analysis showed inconsistent ingredient activity not only between bottles of the same product manufactured by the same company, but also between bottles manufactured by different companies. Assaying for metal contamination found zinc in 88% of bottles and nickel in 40% of bottles. In 37 of 58 bottles tested, fungal contamination was present, with 21 bottles having multiple strains.²⁵

Another study analyzed 41 dietary supplements for the presence of cadmium, lead, and mercury. Results revealed that 68.3% of samples contained contamination with cadmium and lead, and 29.3% with mercury.²⁶ One research team evaluated 121 dietary supplements along with 49 prescription drugs for levels of toxic element contamination. A small percentage of the dietary supplement products exceeded safety levels for mercury, lead, cadmium, arsenic, or aluminum. None of the prescription products exceeded these safety levels.²⁷

Adulterated products contain substances not listed on the product labeling, substitution of inferior materials for active ingredients, or may contain a lesser amount of ingredients. Weight loss, sports enhancement, and sexual function supplements commonly contain banned substances.²⁸

The FDA created and currently maintains the Health Fraud Product Database to increase awareness. This database contains information about products cited in warning letters, advisory letters, recalls, public notifications, and press announcements for various issues. Issues cited include products claiming to cure, treat, or prevent a disease and products containing undeclared ingredients or a new dietary ingredient.²⁹ The database is available in the consumer section of the FDA website at https://www.fda.gov/consumers/health-fraud-scams/health-fraud-product-database.

On January 2, 2022, the FDA issued a warning letter to the manufacturers of Nasitrol, a nasal spray based on the ingredient iota carrageenan. A review of the product’s website found claims that the product is intended to mitigate, prevent, treat, diagnose, or cure COVID-19 in people. Federal regulations define products making these claims as drugs and subject to review by the FDA before approval and subsequent marketing. As discussed earlier, this is in direct violation of federal regulations.³⁰

In another example, on July 15, 2022, the FDA issued a public notice advising consumers to refrain from purchasing Adam’s Secret Extra Strength Amazing Black, a product promoted for sexual enhancement. Laboratory analysis found that the product contained tadalafil, a prescription medication used for erectile dysfunction.³¹ Due to the potential for severe side effects such as hypotension, tadalafil administration requires medical supervision by a physician.³²

A study published in 2018 analyzed FDA warning letters issued from 2007 through 2016, using data from the Health Fraud Product Database. During this time frame, the FDA found 776 adulterated dietary supplements from 146 different companies. A total of 157 products contained more than one unapproved ingredient. Products marketed for sexual enhancement accounted for 45.5% of letters, weight loss 40.9%, and muscle building 11.9%. Unapproved ingredients included sildenafil in sexual enhancement, sibutramine in weight loss, and synthetic steroids or steroid-like ingredients in muscle building supplements.³³

One way for consumers to know they are purchasing a valid product is by looking for a certified product. The certification process involves an independent, third-party company testing a company’s products, offering quality assurance for dietary supplements. Parameters tested include³⁴

• Product contains the ingredients stated on the label
• Presence of harmful ingredients
• Presence of contamination
• Proper dissolution
• cGMP followed during manufacture

Three independent, private, third-party certifying organizations operate in the United States: the US Pharmacopeial Convention (USP), NSF International, and Consumerlabs.com. All three companies offer product certification programs for a fee. Each company allows products passing certification to display a seal on product labeling. Table 3 summarizes information about each organization.

Table 3. Dietary Supplement Certification Organizations

Source: adapted from reference 33

Online product ordering is a convenient shopping option rapidly gaining popularity in recent years, especially during the pandemic. While tempting to order the least expensive product, investigating the source and quality of dietary supplements available online is essential. Proactive training of the entire pharmacy team aids in providing patients with accurate information.

Situation: A weary technician finally finishes ringing out the last customer after two hours straight at the register. A sigh of relief quickly turns into a disgruntled groan as another customer approaches. With a bottle labeled ‘Menopausal Support’ in hand, the customer points to the bottle label and asks, "What does ‘proprietary blend’ mean?" The technician glances over her shoulder, sees the pharmacist engaged in an intense phone conversation, and replies to the customer, "The bottle label clearly lists the ingredients."

Secret #4: Federal regulations define required dietary supplement label information. Unfortunately, ambiguity still exists, making it challenging to identify exactly what the product contains.

Federal regulations define the information required on dietary supplement product labeling in detailed, specific terms. Product labeling must include³⁵

• Product name
• The term ‘dietary supplement’ or similar term (i.e., herbal supplement)
• Name and location of the manufacturer, along with a domestic address and phone number for reporting serious adverse events
• Nutrition labeling in the form of a “Supplement Facts” panel with the following information (see Figure 1):
  • Serving size
  • Number of servings per container
  • Listing of each dietary ingredient in the product
  • Amount of dietary ingredient per serving (Exception: ingredients in a proprietary blend)
  • Amount per serving listed as a quantitative amount by weight, as a percentage of the Daily Value, or as both
• A list of other ingredients not declared on the Supplement Facts label (usually excipients such as preservatives or dyes)
• Net quantity of contents

Figure 1. Supplemental Facts Label (sourced from reference 36)

One area of ambiguity in dietary supplement product labeling is the listing of a proprietary blend. The term proprietary blend refers to a blend of dietary ingredients unique to a manufacturer and product. Federal labeling regulations allow the listing of proprietary blends on dietary supplement products, however, only the total weight of the blend is required, not the weight of individual ingredients.³⁵ There is no way for the healthcare professional or consumer to know exactly how much of a particular ingredient the proprietary blend contains.

Consumerlabs.com cautions consumers about products containing proprietary blends or formulas. In many instances, the blend's name sounds like a desired, expensive ingredient that is only a small part of the formula. Marketing of products containing proprietary blends may mislead the consumer with claims meant to impress the consumer and drive sales of the product.³⁷

FDA regulations do allow structure/function claims on dietary supplement labeling. Structure/function claims describe how a nutrient or dietary ingredient may affect or act to maintain the structure or function of the body.³⁵ Examples of structure/function claims include³⁵

• Calcium builds strong bones
• Antioxidants maintain cell integrity
• Fiber maintains bowel integrity

If a dietary supplement label contains a structure/function claim it must also contain the following statement: "This statement has not been evaluated by the Food and Drug Administration. This product is not intended to diagnose, treat, cure, or prevent any disease."³⁵

The example in this situation involved a product marketed for menopausal support. Menopausal symptoms affect more than 1 million women in the US annually and include symptoms such as hot flashes and sleep disturbances.³⁸ A search of the DSLD using the term ‘menopausal support’ and filtering for on-market products containing the ingredient ‘proprietary blend’ returned almost 3,000 products.⁹ This abundance of products illustrates the ambiguity that exists on dietary supplement labeling.

Pharmacy technicians are often the first line of contact at the pharmacy. Training and development of pharmacy technicians on the facts surrounding dietary supplements empower technicians, allowing them to answer factual questions and provide effective patient education.

Situation: The pharmacy phone constantly rings throughout the day, and today is no exception. The new COVID vaccine is out, and everyone wants to know if the pharmacy has it in stock. Answering yet another call, the technician is surprised when a patient asks to talk to the pharmacist, complaining about dizziness. The pharmacist checks the patient’s profile, finding no underlying causative medication. Further questioning the patient, the pharmacist uncovers the recent addition of melatonin at night for sleep.

Secret #5: Like prescription medications, dietary supplements have pharmacologic and physiologic effects on the body, potentially resulting in health risks and side effects.

Consumers perceive dietary supplements as safe due to their source from natural substances. While generally well tolerated, dietary supplements affect the body like prescription medications, capable of producing an undesired effect. Lack of regulatory oversight allows products to reach consumers without adequate safety evaluation.

Information describing adverse effects of dietary supplements is anecdotal, derived from case reports and reports submitted through the FDA Safety Reporting Portal. Most dietary supplements have not been studied in pregnant or lactating women or children.

A study published in 2015 evaluated ten years of emergency room data to assess the number of annual visits resulting from dietary supplement adverse events. The authors calculated an average of more than 23,000 emergency room visits stemmed from the consumption of dietary supplements, resulting in more than 2,000 hospitalizations annually.³⁹

Events in older adults accounted for the highest percentage of visits, with 40% of visits due to difficulty swallowing. Incidence in young adults aged 20 to 34 was significant at 28% and primarily involved weight loss and energy products. Side effects reported include heart palpitations, chest pain, and tachycardia.³⁹

Unsupervised child ingestions accounted for 21% of visits. Unlike prescription medications, regulations do not require child-resistant packaging for dietary supplements, except for iron-containing products.³⁹ The authors note the numbers evaluated in the study are likely underreported as patients do not always include dietary supplements with the current medication list.³⁹

Table 4. Adverse Effects of Common Dietary Supplements^7,17

Patients often fail to report usage of dietary supplements and most pharmacy software lacks the ability to note dietary supplement usage in the patient profile. In this situation, the pharmacist took the extra time to further question the patient about dietary supplement usage and successfully identified the causative agent.

Pause and Ponder: In what ways could you incorporate activities into the daily workflow to increase awareness of patients’ use of dietary supplements?

Situation: Today, the workload in the pharmacy is lighter than usual. With a grateful sigh, the pharmacist sinks onto a stool reaching for a quick snack. Then the phone rings… The caller is a triage nurse from the local hospital to verify a patient’s medication profile. Pulling up the profile, the pharmacist verifies the list of medications, including digoxin. The triage nurse confirms atrial fibrillation as the cause for admission, adding that the patient recently started taking St. John’s Wort for depression.

Secret #6: Some dietary supplements affect the CYP450 liver enzymes, potentially altering the pharmacokinetics of medications, leading to treatment failure and/or toxicity.

Dietary supplement-drug interactions

Drug-drug interactions result in altered absorption, metabolism, or excretion. Drug-dietary supplement interactions occur through the same pathways as those used by FDA-approved drugs. The cytochrome P450 (CYP P450) enzymes in the liver are responsible for the metabolism of most medications.^41,42 The ability of a drug to either induce or inhibit these enzymes is a significant factor in drug-drug interactions. The natural ingredients found in dietary supplements are capable of inhibition or induction, also having the potential to interact with medications.

St. John’s Wort, an herbal commonly taken for the relief of mild to moderate depression, induces the activity of CYP3A4.^43,44 This induction increases the clearance of medications metabolized by CYP3A4. Examples of medications cleared by CYP3A4 include alprazolam, atorvastatin, cyclosporine, oral contraceptives, oxycodone, and warfarin.^43,44 Patients need counseling about potential drug interactions with St. John’s Wort.

Limited clinical studies evaluating the impact of drug-dietary supplement interactions exist. Many interactions are theoretical, based on limited clinical evidence, animal research, and case reports.⁷ 

Table 5. Examples of Potential Drug-Dietary Supplement Interactions^7,17

Pharmacy training emphasizes the importance of drug-drug interactions. It is important to remember that any substance introduced to the body, including food, beverages, and dietary supplements, has the potential to interact with medications.

Situation: It is another busy day in the pharmacy; prescriptions cover the bench, the phone rings constantly, and a pickup queue extends around the corner. A technician nervously approaches the pharmacist about a patient at the counter with a question regarding a supplement. The pharmacist throws down the spatula, muttering angrily about lacking the knowledge and training to answer the question properly. Sighing, he says, "I’ll just Google it."

Secret #7: Many websites provide clinically backed information on dietary supplements (and Google is not one of them!).

The vast amount of health information available via the Internet with just a few clicks of the keyboard is both a blessing and a curse. Google is now a verb, and a simple search returns millions of results in seconds. While this may seem like a blessing, the curse lies in the searcher's inability to recognize valid, accurate sources of information. In many searches, ads appear as search results adding to the confusion.

In addition to the Internet, consumers turn to social media for health information. Social media use increased from 27% in 2009 to 86% in 2019.⁴⁵ Information posted on social media provides communication about healthcare issues, potentially resulting in improved health care.⁴⁵ Unfortunately, inaccurate information abounds on the Internet and social media platforms, leading to consumer misinformation.^47-49

The FDA recently launched a new dietary supplement education initiative geared towards consumers, healthcare professionals, and teachers. The program, Supplement Your Knowledge, presents information about dietary supplements through a series of three videos. Educational materials, including fact sheets and infographics, are available in English and Spanish.⁵⁰

Many government agencies provide free access to information about dietary supplements and their side effects, toxicity, and drug interactions. There are also several paid subscription resources available. Table 6 lists many of the available information options.

Table 6. Sources of Information about Dietary Supplements

Performing an Internet search via Google may seem like the quickest and easiest way to find the answer to an inquiry. Engaging with the patient, gaining additional information, and knowing where to look ultimately saves time. It is not necessary for one to be an expert in all dietary supplements, just to self-educate one supplement at a time.

Pause and Ponder: A patient shares the unfortunate news about a recent cancer diagnosis. He asks you about the use of herbs in the treatment of cancer. What advice would you give? 

Conclusion

You may have noticed a recurring theme throughout this activity. Education. Dietary supplement education is essential to patient safety given the current usage patterns and accessibility of the retail pharmacy team. Education needs to include the entire pharmacy team. Technicians are often the first point of contact at the pharmacy, commonly fielding patient questions. Knowing when to answer questions and when to involve the pharmacist is a necessary skill. Understanding the differences in oversight, the physiological effects of dietary supplement consumption, and the potential for drug interactions allows effective management and counseling of patients. It is important for healthcare providers to solicit information regarding patient consumption of dietary supplements.

Sidebar: Tips for Counseling Patients about Dietary Supplements

Carefully inspect the product to ensure intact product labeling

Ensure the safety seal is intact

Check for an expiration date or best used by date

Check for customer service or return information before ordering

Buy direct from a reputable company; many reputable companies sell through Amazon, avoid 3^rd party resellers

Check for the presence of a third-party certification seal

Before purchase, check the company’s website for information on quality standards

Pay attention to the appearance and smell of the product upon opening

Child-resistant packaging is not a requirement for dietary supplements; advise on proper storage of product

Reinforce the importance of including dietary supplements on a current medication list

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