Risks Associated With Excessive Weight Loss

Definition/Introduction

With global obesity on the rise, the number of dietary, surgical, exercise, lifestyle, and pharmacological approaches to weight loss has expanded. Although these modalities share a common goal of body mass reduction, results differ in amounts of weight loss, sustainability, and the potential for long-term maintenance. There is no single definition of "excessive" weight loss; however, weight loss >10% of body weight has been defined as "large" weight loss.[1] Loss of approximately 5% to 10% of body weight over 6 months has improved glycemic control and clinically reduced blood pressure and cholesterol. Losing more than this, or weight loss at faster rates, may improve overall health but may increase the possibility of health risks.[2][3][4]

Issues of Concern

Weight loss is an important component of addressing medical concerns about obesity; it also affects physical appearance, athletic pursuits, and personal motivators.[5][6] Options for achieving weight loss goals include diet, surgery, and medication; however, short-term versus long-term success in weight loss varies.

Dietary Options

A multitude of fad diets have emerged. Some of the most popular include the following:

• The ketogenic diet
• The Atkin’s diet
• The paleolithic diet
• Intermittent fasting [7] 

Medication Options

The following weight loss medications have been approved by the US Food and Drug Administration (FDA) and demonstrated effectiveness in weight reduction:

• Orlistat (1999)
• Phentermine and topiramate (2012)
• Naltrexone and bupropion (2014)
• Liraglutide (2014)
• Semaglutide (2021) [8][9] 

Surgical Options

Bariatric surgeries, including sleeve gastrectomy, gastric bypass, gastric band, and duodenal switch, alter gastrointestinal anatomy, reduce gastric size, and change absorptive patterns. These surgeries can lead to >20% total weight loss in upwards of 90% of patients by 2 years postoperatively, and 70% of those individuals have been able to maintain that weight loss at 10 years.[10][11] 

Whether weight loss occurs rapidly or gradually over time, it can be linked to various challenges, including macronutrient and micronutrient deficiencies, electrolyte imbalances, metabolic shifts, psychological effects, bone density changes, and even death.[12][13][14] The rate at which weight loss is achieved has associated risks and benefits. Recognizing and addressing these risks, often with the assistance of skilled professionals in a multidisciplinary approach, is crucial in fostering a customized, sustainable, and comprehensive approach to weight loss that prioritizes the overall well-being of an individual.[15]

Clinical Significance

Dietary Risks of Excessive Weight Loss

Many dietary interventions have been created to achieve desired weight loss. Many reduce caloric intake, with some diets excluding macronutrients or specific food groups altogether. Fad diets have also gained popularity, claiming to reduce weight quickly.[7] Three major categories of diets include the following:

• Diets decreasing or increasing macronutrient composition (eg, low-carbohydrate, low-fat, or high-protein diets)                                                                                                                                                  
• Diets restricting caloric intake based on timing (eg, fasting and intermittent fasting)                                          
• Diets restricting entire food groups (eg, vegetarian, vegan, or carnivore diets)

Some of the most heavily studied of these diets include the ketogenic diet, Atkins diet, paleolithic diet, intermittent fasting, and vegetarian and vegan diets.[7] 

Ketogenic Diet

The ketogenic diet, popularized in the 1920s, involves restricting carbohydrate intake to <50 g daily (the recommended daily value of carbohydrates is 130 g).[16][17][18] This diet is often used by individuals wishing to lose weight rapidly in the short term, with some reports of people losing up to 9.9 pounds (4.5 kg) in 2 weeks and up to 57.3 pounds (26 kg) if maintained over 2 years.[19][20] 

Risks include vitamin and mineral deficiencies.[19] For individuals undergoing a 12-week ketogenic diet, magnesium, calcium, iron, phosphorus, and potassium levels were found to be less than the recommended values. Although this was not evident in serum levels at the end of the study, it could indicate deficiencies if the ketogenic diet were extended beyond those 12 weeks.[21] Hypercalciuria and renal stones have also been reported as long-term adverse effects of the diet.[22] Short-term risks include gastrointestinal effects such as nausea, vomiting, and decreased energy. These symptoms usually last from a few days to up to 2 weeks and are sometimes referred to as the "ketogenic flu."[23] 

Atkins Diet

The Atkins diet, created in the 1960s, is similar to the ketogenic diet, restricting carbohydrates and promoting increased fats and proteins.[24] However, it differs in that it slowly increases carbohydrates through different program phases. The first 2 weeks of the diet constitute an induction phase, with <20 g of carbohydrates consumed daily (even less than the ketogenic diet). In the second phase, carbohydrates are increased to 40 to 90 g daily, ideally for life.[7] 

A study comparing females who lost similar amounts of weight through different diets over 8 weeks determined that those on the Atkins diet were found to be at risk for deficiencies in thiamine, folic acid, vitamin C, and zinc.[25] These deficiencies can be dangerous, with possible symptoms such as ataxia and peripheral neuropathy.

• Thiamine deficiency can lead to nystagmus.                                                                                                         
• Folate deficiency has been associated with cognitive impairment, dementia, and depression.                                       
• Zinc deficiency has been linked to poor wound healing, dermatological symptoms, and easy bleeding.                     
• Vitamin C deficiency manifests as fatigue, muscle cramping, gingival inflammation, and gingival hypertrophy in some cases.[26][27][28][29]

Paleolithic Diet

The paleolithic diet, introduced in the 1980s, focuses on eliminating processed foods and only consuming lean meats, fruits, nonstarchy vegetables, nuts, and seeds while restricting dairy products.[30] Individuals adhering to this diet over 12 weeks were found to have weight loss as high as 4% to 6% of their starting body weight.[31] There is limited research regarding long-term adherence and sustainability. Because this diet is rich in potassium, there is a concern for hyperkalemia in individuals with renal impairment.[32] Other risks associated with this diet include calcium deficiency, with consumption of 50% less than the daily recommended value.[33] This deficiency may not be harmful in the short term; however, long-term calcium deficiency has been associated with osteopenia and osteoporosis.[34][35] 

Vegetarian and Vegan Diets

The vegetarian diet, characterized by eliminating meat, seafood, and poultry, is followed for various reasons, including ethical considerations, religious beliefs, cultural motivations, and health concerns.[36] Risks associated with this diet include an increased risk of certain micronutrient deficiencies, including B12, calcium, zinc, iron, vitamin E, and some fatty acids.[37] These microdeficiencies often manifest as anemia, reduction in bone density, fatigue, and sometimes growth delays in children.[38] Similar risks are associated with the vegan diet, which eliminates all animal products from the diet.[39] 

Intermittent Fasting

Intermittent fasting, thought to improve metabolic and glycemic control, is defined as abstinence from food for a given amount of time followed by a meal. There are many different approaches, including alternating days in which food is consumed or limiting food consumption to a time window such as 8 hours.[7] Short-term risks identified over 1 to 3 months include headache, lethargy, and dizziness secondary to lack of fluid, hypoglycemia, and, in some cases, electrolyte imbalances.[40] 

Fluid and Caloric Restriction

Rapid weight loss, induced by intense dieting, extreme exercise, fluid restriction, medication use, or fasting without electrolyte supplementation, can lead to a series of adverse effects with electrolyte derangements, decreased athletic performance, hormone imbalance, and potential organ damage.[12][41] 

Intermittent and long-term fasting can result in sodium, potassium, and uric acid imbalances due to fluid shifts, reduced electrolytes, and reduced water uptake.[42][43][44] These shifts are typically transient, and electrolyte levels tend to normalize once the body reestablishes fluid balance.[45] Athletes often employ fluid or calorie restrictions over short periods to induce rapid weight loss. This method is often used in combat sports to rapidly lose weight, pass a pre-competition weight test, and perform in a lower-weight class. The use of laxatives, diuretics, and sweating via saunas represent additional approaches athletes use to achieve rapid weight loss, with most weight loss attributed to water weight.[46] Contestants can lose up to 6% of total body weight quickly, regaining as much as possible after weigh-in but before a competition.[47] 

Fluid and calorie restriction usually begins 2 days before a competition, although it can be more or less depending on the athlete.[48] Termed "weight cycling," this method adversely affects physical health and performance. Other detrimental effects include emotional lability with increased tension, anger, and confusion.[49] In some cases, testosterone levels decreased, while ammonia, uric acid, and insulin serum levels increased following weight cycling.[50] Although the long-term effects remain unclear, eating disorders such as binge eating have been reported to be associated with this method of weight loss, affecting individuals long after they are done competing.[51] Screening for such disorders may prove advantageous in providing early intervention, resources, and support. 

Fluid restriction can also lead to elevations in serum creatinine. Such practices can lead to acute kidney injuries, and if dehydration persists, the severity of these injuries may worsen over time. These acute shifts have not been associated with sustained weight loss. If individuals adhere to well-balanced diets without restricting fluids, electrolyte disturbances are less likely.[52][53] Beyond these short-term concerns, weight loss may also introduce metabolic risks. 

Metabolic Changes

Homeostasis occurs in each human body at a different level of weight. Each person has a resting metabolic rate, defined as the rate of energy production and expenditure needed to function while at rest.[54] After weight loss, the resting metabolic rate slows, likely to counter weight loss and return to homeostasis.[55] It is hypothesized that due to this phenomenon of "metabolic adaptation," weight regain is likely even after weight is lost.[56][57] Alterations in body mass can cause a shift in homeostasis, influencing the delicate balance of anorexogenic and orexigenic hormones that regulate satiety and hunger.[58] This can lead to changes in the body's ability to sense satiety.[59]

Anorexogenic hormones, such as leptin, peptide YY, and cholecystokinin, play a crucial role in signaling satiety, communicating to the brain that the body does not require additional calories. Orexigenic hormones, like ghrelin, stimulate hunger. During dieting and caloric restriction periods, orexigenic hormones increase, and anorexigenic hormone levels decrease.[60] Even after weight loss, the drive to eat remains heightened, potentially indicating the risk of weight regain.[61] Hormone levels may never revert to their pre-dieting states. These ongoing hormonal imbalances increase individuals' challenges in maintaining long-term weight loss.[59][58] 

Thyroid hormones, T3 and T4, have been identified as contributors to weight loss, with medications and supplements targeting thyroid hormones becoming another method utilized. Desiccated thyroid extract can be used to treat hypothyroidism in individuals, but it has also been shown to aid in weight loss compared to individuals taking levothyroxine.[62] Some thyroid hormones, such as T3, promote energy expenditure in their active state. For thyroid hormones to become active, they must convert from their inactive form, T4, to their active form, T3.

With weight loss, there is a reduction in the peripheral conversion of the prohormone to T3. Despite this decrease in conversion, individuals with higher baseline levels of free T3 and T4 have been associated with larger weight loss over time.[63] This implies that, alongside alterations in anorexogenic and orexigenic hormones, the balance of thyroid hormones may also play a role in an individual's weight loss.[63] Desiccated thyroid hormone has become an aid in weight loss, and numerous other weight loss medications are currently available.[62] 

Risks Associated With Weight-Loss Medications

Medications, including orlistat, phentermine and topiramate, naltrexone and bupropion, liraglutide, and semaglutide, have obtained FDA approval for weight loss in the United States, and all are effective for weight loss.[8] FDA guidelines recommend that consideration for these medications include a body mass index (BMI) >30 or ranging from 27 to 30 with an obesity-related comorbidity (type 2 diabetes, hypertension, or any other disease secondary to obesity).[64] 

There are both over-the-counter and prescription anti-obesity medications. One over-the-counter weight loss option in the United States is orlistat, which was FDA-approved in 2007.[65] Although not approved for weight loss, other medications have demonstrated weight reduction effectiveness. Desiccated thyroid extract, used in treating hypothyroidism, has been shown to reduce weight by at least 4 lb (1.8 kg) over 6 months compared with individuals taking levothyroxine.[62] Medications, such as diuretics and laxatives, are often used in sports for rapid weight loss but are ineffective long-term and are not FDA-approved for this use.[66] 

When weight loss medications are considered, individuals should be educated that they will likely be on anti-obesity medicines for life, as obesity is a chronic disease, often relapsing if pharmacotherapy is ceased.[64] Sustained results are demonstrated when individuals actively engage in lifestyle modifications such as dieting and exercise concurrently with medication.[67] Despite weight loss medications effectively causing >5% body weight loss in most individuals, undesirable adverse effects are common. 

• Phentermine and topiramate: A prescription appetite suppressant combining the weight loss medication phentermine and the anti-epileptic medication topiramate.[64] Although it has proven efficacious in long-term weight loss, it is contraindicated in pregnancy, with a reported risk of oral cleft palate or cleft lip in infants in the first trimester.[68][69] Individuals considering this medication should undergo pregnancy testing before it is prescribed. Other risks include dizziness, constipation, dry mouth, and inattention.[70] 

• Naltrexone and bupropion: A prescription weight loss medication that decreases appetite and cravings. It has been linked with dizziness, anxiety, insomnia, and, in some cases, psychosis. It also lowers the seizure threshold, increasing the risk of seizures. Other more common adverse effects include hypertension, nausea, and vomiting.[71] 

• Liraglutide: A prescription medication glucagon-like peptide-1 analog, delaying gastric emptying and increasing satiety.[72] It has been linked with gastrointestinal symptoms such as nausea and vomiting. It also has an increased risk of pancreatitis. In animal models, the development of medullary thyroid cancer has occurred. Although this has not been found in human studies, liraglutide is contraindicated if a family history is present.[73] 

• Semaglutide: A prescription glucagon-like peptide-1 analog, demonstrating a total weight loss of 14.9% over a 68-week study.[74] Risks include hypoglycemia and gastrointestinal side effects such as nausea, vomiting, and abdominal cramping. Like liraglutide, there is a small risk of pancreatitis and thyroid cancer in animal studies; however, studies did not demonstrate any associated risk in humans.[75]

• Orlistat: An over-the-counter medication in the United States, it reduces fat absorption by up to 30%. This medication is mainly associated with gastrointestinal adverse effects. It has been shown to cause fatty stools, fecal urgency, incontinence, and increased defecation. These adverse effects decrease the longer an individual stays on the drug.[76] 

Considering these potential side effects, weight loss medications should be chosen to fit the patient's best interests and needs.[77] This can lead to successful, sustained weight loss in many individuals.[67] In some cases, patients have even utilized weight loss medications to avoid weight regain postbariatric surgery.[78] Other individuals may be more appropriate for bariatric surgery than medication alternatives. Bariatric surgery may be appropriate for individuals who meet certain criteria, such as a BMI >40 or greater than 35 with a comorbidity, but it is associated with risks. 

Bariatric Surgery Risks

Bariatric surgery, coming into existence in the 1950s, has become a method for rapid weight reduction exceeding 20% of total body mass in some cases.[10][79] Surgery may be appropriate for individuals who have a BMI >40 or >35 with an underlying health condition, such as diabetes mellitus.[80] The 2 most common bariatric surgeries performed worldwide are the sleeve gastrectomy and the gastric bypass.[81] 

The sleeve gastrectomy removes a portion of the stomach, including the fundus. This leaves a small, more slender gastric pouch attaching the esophagus to the duodenum, restricting the amount of food able to be stored in the stomach.[82] With food restriction in the stomach, weight loss is achieved by reducing the quantity of food consumed and adequately absorbed during each meal.

Gastric bypass involves restricting the size of the gastric pouch and rerouting that pouch to the jejunum, bypassing the duodenum and most of the stomach. This creates less space for caloric absorption.[83] By decreasing the space, less food is consumed due to the sensation of satiety also occurring, leading to decreased caloric intake.

Like any surgery, there are short- and long-term risks. Postoperative complications do occur but are low at 2.12% in sleeve gastrectomy patients and 3.02% in gastric bypass patients.[84] Early complications (within 30 days postoperatively) can include bleeding at suture or staple lines, abscesses, and infections. Pancreatitis has also been reported in a small percentage of patients, ranging from 0.4% to 1.04%, but it is hypothesized that patients with choledocholithias before bariatric surgery are at higher risk.[85] Perioperative mortality rates are low, ranging from 0.03% to 0.2%, much improved from rates in the early 2000s.[10] When considering bariatric surgery for patients, multidisciplinary team members should counsel patients on the benefits and the risks of surgery and do a thorough preoperative physical examination, laboratory evaluation, and medical history to identify appropriate candidates.

Aside from immediate postoperative complications, chronic long-term complications include nutrient deficiencies secondary to anatomical changes that can be present for life. Iron, vitamin B12, copper, and calcium malabsorption after gastric bypass likely occur due to bypassing the duodenum and proximal jejunum, where much of the absorption occurs.[86][87] Copper deficiency often mimics B12 deficiency, making it more difficult to identify. Anemia has also been reported after bariatric surgery, which in part may be secondary to decreased iron absorption and folic acid absorption.[88] B12 deficiency has also been linked to macrocytic anemia, with long-term deficiency resulting in neurologic symptoms such as paresthesias and ataxia. Obtaining a baseline complete blood count and metabolic panel before surgery aids in determining if patients are at higher risk for chronic deficiencies. Follow-up laboratory evaluation is provider-dependent but is often performed in routine postoperative follow-ups to ensure no significant abnormalities are present.

Dumping syndrome (accelerated gastric emptying after meals) has also been reported amongst bariatric patients, especially those with gastric bypass, with resolution usually by 2 years postsurgery.[89][90] Although the pathophysiology is still uncertain, it is thought to be secondary to the rapid movement of chyme due to alterations in anatomy preventing digestion. Symptoms can be improved with small, frequent meals instead of large ones. Patients should receive counseling on this possible risk.[91] Often, bariatric surgeries are completed with a multidisciplinary approach to the patient, involving multiple specialties. Some of these specialists include nutritionists and dieticians who provide assistance with supplementation as needed, primary care clinicians who manage underlying comorbidities, weight-loss coaches, and exercise trainers. Continuous follow-up reviews and guides patient progress. 

Muscle and Bone Mass Effects

Regardless of how weight is lost, it is not limited to only the loss of adipose tissue. It can also affect fat-free mass, such as muscle and bone. During a 16-week weight loss program that included individuals with a BMI >30, on average, 13% of baseline weight was lost. Total lean mass was also reduced by 3.8%. Despite the reduction in lean mass, however, strength did not seem to be adversely affected.[92] Moderate exercise and strength training have been suggested to combat muscle reduction. Over 12 months, 2 groups underwent weight loss with either calorie restriction or exercise. Both groups lost a similar amount of weight. Utilizing MRI, muscle mass was significantly decreased in the calorie restriction group but not in the exercise group.[93] This implies that by incorporating exercise and caloric restriction into a weight loss regimen, individuals can decrease fatty tissue while preserving muscle mass. 

In addition to decreased muscle mass, rapid loss of adipose tissue reduces the load on the skeletal system over time, leading to a higher risk of osteoporosis.[94] Throughout a 24-week caloric restriction diet, women averaging the age of 38 years lost more than 16 kg. At the end of those 24 weeks, they had significantly decreased bone mineral density along the femoral neck and greater trochanter.[95] Even greater bone loss has been associated with weight loss in individuals not obese at baseline.[96] Weight reduction in postmenopausal women is associated with bone mineral loss ranging from 1% to 4% compared with premenopausal women.[94] These findings raise concern for potential fractures or even increased morbidity and mortality. As part of counseling patients in weight loss, education must be provided on the risks of osteoporosis, with weight training being a vital exercise method to reduce the risk for osteoporosis. 

Death

Restrictive diets have been associated with an increased risk of death. For example, low-carbohydrate diets, such as Atkins, are significantly associated with increased all-cause mortality.[97][98] A prospective cohort study in Japan determined that a low-carbohydrate diet supplemented with high animal protein and fat and a high-carbohydrate diet supplemented with low animal protein and fat were both associated with increased mortality. In contrast, a low-carbohydrate diet supplemented with high plant protein and fats was associated with a lower mortality rate. This suggests that carbohydrate reduction may not increase the risk of death, but rather, the diet as a whole increases the mortality rate.[99] When considering restrictive diets, patients and multidisciplinary weight-loss team members should be aware of the risks and benefits of the diet chosen.

Beyond the diets themselves, the magnitude of weight loss may also be associated with mortality. In 2010, a longitudinal cohort study analyzed weight loss in 6117 Americans 50 years and older over 3 years. It recorded 1602 deaths occurring within that period. There was an association between weight loss of 15% or more and increased risk of death from any cause. This was regardless of the maximum BMI at the time of death.[100] This implies that large amounts of weight loss may be detrimental to an individual by increasing the risk of death. Underlying comorbidities may further exacerbate the risk of mortality. The rapid and large fluctuations in weight commonly seen in eating disorder patients may also play a role in these risks. 

Psychiatric disorders, which can manifest in the form of an eating disorder, can cause rapid weight loss.[101] Eating disorders can be associated with rapid weight changes, often related to severe restriction or significant purging. Anorexia nervosa and bulimia are 2 of the most common eating disorders, resulting in numerous medical complications such as electrolyte abnormalities, kidney disease, hematemesis, elevated liver transaminases, and even death.[102] These disorders can be seen in all stages of life and can lead to death in severe cases.[103] Driven by an individual's fear of weight gain, these diseases have considerable morbidity and mortality.[104] These findings exemplify that weight loss can also be associated with psychological risks. A multidisciplinary team should carefully monitor and assess an individual's mental health when considering weight loss for a patient.

Psychological Effects

Weight loss has been associated with psychological disturbances, including depression, anxiety, binge eating, and an obsession with food.[105] Rapid weight loss, while it can be successful in the short term, is challenging to sustain and can lead to secondary effects such as irritability, fatigue, and anger.[106] In bariatric surgery patients, depressive symptoms and impulsivity in association with food have led to suboptimal results regarding weight loss and maintenance.[107][108] These psychological difficulties can be lessened with the help of cognitive behavioral therapy or psychotherapy, helping patients find tools to grapple with their challenges.[109] Weight loss requires a multidisciplinary approach, with a team of healthcare professionals who can hone in on specific challenges each patient may experience.

Nursing, Allied Health, and Interprofessional Team Interventions

As the variety of diets, surgeries, and weight loss medications expand, individuals are increasingly inclined to engage in weight loss without understanding the associated risks.[59][110] Body mass reduction, if desired by an individual, can be achieved in numerous different ways. Many fad diets have been associated with nutrient deficiencies, at least in the short term, and these diets have proven difficult to maintain in the long term.[7] Metabolic shifts in satiety and hunger hormones also have a role in long-term weight maintenance and can potentially increase the likelihood of weight regain.[111] Bariatric surgery can be effective but does not come without significant risks, the possibility of surgical complications, and the tendency for nutrient deficiencies.[10] Weight loss medications are effective but have adverse effect profiles that patients should be properly educated on.[64] The risk of death also increases with some of the weight loss methods.[100] 

Individuals should receive adequate education before choosing a weight loss plan.[112] Recognizing that no one-size-fits-all approach is paramount, as each individual is unique, driven by different motivators, and possesses distinct physiological and psychological needs.[113] This complexity necessitates a collaborative team of professionals with diverse knowledge to guide individuals effectively. This multidisciplinary team can include primary care managers, endocrinologists, surgeons, psychiatrists, psychologists, dieticians, nutritionists, nurses, pharmacists, physical therapists, and personal trainers. Together, the team can enhance patient outcomes by pooling diverse expertise and adopting varied approaches to wellness. This interprofessional approach acknowledges each patient's unique needs and leverages various healthcare professionals' strengths to create a more effective and tailored weight loss strategy.[114]

Weight loss education can start at a nursing or primary care clinician's level with counseling regarding lifestyle modifications. Bloodwork can be assessed to determine if a patient needs extra dietary supplementation due to deficiencies in vitamins or minerals. Counseling can start small by encouraging a daily dietary plan, exercise diary, and lifestyle modifications. In addition to the primary care clinician, a nutritionist can be consulted to provide additional expertise and expand on dietary options. This collaboration provides different insights and helps break down and create a plan for healthy weight loss. Follow-up via messaging and in-office visits every 2 weeks or more often, depending on the patient's needs, can benefit long-term weight loss success.[112][115] 

Follow-up can be short-term (days to weeks) or long-term (months to years) based on the patient's needs.[116] Supportive psychotherapy and group therapy have also proven helpful. Psychiatrists and psychologists can add strategies that incorporate mental health and improve psychological barriers to weight loss, such as depression and anxiety.[109][117] 

Patients with weight loss challenges that require more than support, diet, and lifestyle changes may benefit from weight loss medications in conjunction with the above strategies. Clinical pharmacists can assist with counseling and continuously follow up on medications, determining the correct dosage and type of weight loss medication for individuals.[118] By fostering a holistic understanding of the complexities involved and providing a tailored support program with an interprofessional team, patients can make informed choices prioritizing their short- and long-term weight loss goals to successfully achieve their desired results. 

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Disclosure: Kerry Jaime declares no relevant financial relationships with ineligible companies.

Disclosure: Victoria Mank declares no relevant financial relationships with ineligible companies.