WEIGHT

A SCIENTIFIC LOOK AT ALTERNATIVE MEDICINE

Diets and Weight Loss

Thomas J. Wheeler, PhD

Associate Professor (retired), Department of Biochemistry and Molecular Biology,

University of Louisville School of Medicine, Louisville KY

thomas.wheeler@louisville.edu

Revised 2022

This material was originally part of a handout for an elective course given to

medical students at the University of Louisville.

DISCLAIMER: The material presented here is not medical advice. It represents the author's summary of scientific evidence concerning various topics. For medical advice, see your physician.

A pdf file of this article (39 pages) is available at this site: weight22.pdf

Note: in quoted material, reference numbers in the original have been omitted here.

CONTENTS

Overview: definition and marketing

Diets - general points

Diets - critiques

Reviews of multiple diets

Some popular diets

Supplements for weight loss

Some components of diet products

Reviews of multiple products

Critiques of weight loss supplements

Adverse effects

Alphabetical listing of individual weight loss supplements

Other approaches

References

OVERVIEW

Many people are greatly concerned with being overweight, for reasons of health and/or appearance. Dieting and weight loss are major areas for "alternative" products and advice. A new best-selling diet book appears nearly every year. Diet plans, supplements, and other approaches are marketed.

DIETS - GENERAL POINTS

"Data from the US National Health Interview Survey (NHIS) reveal a stable use of special diets over the 2002-2012 period, with approximately 3% of American adults reporting the use of one or more special diets (i.e. vegetarian (including vegan), macrobiotic, Atkins, Pritikin, and Ornish diets) for a period of ≥2 weeks in the past 12 months...However, it is possible that the prevalence of use of special diets in this population has been underestimated. One reason for this is that the list of diets included in the NHIS was not exhaustive. That is, there are a variety of special diets (e.g. DASH, Mediterranean, the Zone, Weight Watchers, South Beach, Raw Food, gluten-free, low FODMAP (fermentable oligosaccharides, disaccharides, monosaccharides and polyols) that are now popular among the public but were not included in the NHIS and thus, could not be assessed" (Leung et al. 2018. Nutr Health. 24(1):11-8).

"Under the Affordable Care Act, basic obesity screening must be covered by insurance, and some obese patients may qualify for additional counseling. Twenty-three states require some type of coverage for nutritional and obesity therapy, which can include weight-loss programs. In 23 states, insurers must cover weight-loss surgery, according to an analysis in 2014 by the National Conference of State Legislatures...Even with attentive doctors at the helm, these clinics often employ techniques that are unproven and even some that have been discredited" (Abrams and Thomas 2015 July 4. In health law, a boon for diet clinics. New York Times).

Some other general points:

It is important that a diet provides adequate nutrition (protein, vitamins, minerals, calories), and that there is an appropriate balance of carbohydrate, protein, and fat. Potential beneficial antioxidants, phytochemicals, and omega-3 fatty acids should also be considered.
Rapid weight loss is often seen in the early stages of a diet, but this may be mostly water. However, Hale (2021 Sep 15. Examining common obesity myths. Center for Inquiry) considers it a myth that "losing weight quickly isn't a good strategy for long-term weight loss." A study found "Those who lost weight quickly obtained greater weight reduction and long-term maintenance and were not any more likely than gradual weight losers to regain weight."
Most people who lose weight on a diet later regain it. "After the initial weight loss owing to severe caloric restriction, studies indicate that up to two-thirds of the lost weight is regained within one year, and almost all of it is regained within five years. In many cases, weight increases beyond baseline. This is because diets rarely teach people how to eat healthily in a sustainable way. As a result, people often rebound from one fad diet to the next, perpetually trying and failing to implement long-term change" (Tiller 2021 Nov 18. Diets, detox, and other delusions. Skeptical Inquirer).
"In most cases, as long as macronutrients (protein, fat, carbohydrate) and energy intake are equal, meal frequency does not significantly influence weight loss. You don’t have to eat every 2-3 hours to maximize fat loss" (Hale 2022 Jan 10. Don't fall for New Year's fitness and health myths. Center for Inquiry).

DIETS - CRITIQUES

Marton et al. (2020. Palgrave Commun 6:43) examined 100 best-selling nutritional books. "Weight loss was a common theme in the summaries of nutritional best-selling books. In addition to weight loss, 31 of the books promised to cure or prevent a host of diseases, including diabetes, heart disease, cancer, and dementia; however, the nutritional advice given to achieve these outcomes varied widely in terms of which types of foods should be consumed or avoided and this information was often contradictory between books. Recommendations regarding the consumption of carbohydrates, dairy, proteins, and fat in particular differed greatly between books...Of 20 authors who had or claimed university affiliations, seven had a current university appointment that could be verified online in university directories...Notably, several of these authors seemed to have become wealthy entrepreneurs."

"Many clinics also sell patients a three- or six-month program that consists of some combination of diet supplements, nutritional counseling and medication. Many of the supplements, like injections of B-12 and other vitamins, are backed by little, if any, scientific evidence for promoting weight loss...Dr. [Michael] Jensen, the Mayo Clinic obesity researcher, studied the effectiveness of weight-loss programs and found that patients who used short-term treatments were not able to keep the weight off. 'Essentially, if you didn’t have a year in the program, the results were horrible,' Dr. Jensen said. If a patient is hoping for long-term results, 'a three- to six-month program is almost as effective as no program'” (Abrams and Thomas 2015 July 4. In health law, a boon for diet clinics. New York Times).

REVIEWS OF MULTIPLE DIETS

Sacks et al. 2009. N Engl J Med. 360(9):859-73: "Reduced-calorie diets result in clinically meaningful weight loss regardless of which macronutrients they emphasize."
Johnston et al. 2014. JAMA. 312(9):923-33: "Among 59 eligible articles reporting 48 unique randomized trials (including 7286 individuals) and compared with no diet, the largest weight loss was associated with low-carbohydrate diets...and low-fat diets...Weight loss differences between individual diets were minimal. For example, the Atkins diet resulted in a 1.71 kg greater weight loss than the Zone diet at 6-month follow-up...Significant weight loss was observed with any low-carbohydrate or low-fat diet. Weight loss differences between individual named diets were small. This supports the practice of recommending any diet that a patient will adhere to in order to lose weight."

SOME POPULAR DIETS

Atkins - see also low carbohydrate. An article by the Mayo Clinic (2022 May 12. Atkins Diet: What's behind the claims?) made the following points:

"The Atkins Diet is a popular low-carbohydrate eating plan developed in the 1960s by heart specialist (cardiologist) Robert C. Atkins. The Atkins Diet restricts carbs (carbohydrates) while focusing on protein and fats."
"The Atkins Diet has several phases for weight loss and maintenance. It starts out with a very low-carbohydrate eating plan."
"The main dietary focus of the Atkins Diet is eating the right balance of carbohydrates, protein, and fats for optimal weight loss and health. The Atkins Diet notes that obesity and related health problems, such as type 2 diabetes and heart disease, are the fault of the typical low-fat, high-carb American diet. The Atkins Diet says that you don't need to avoid fatty cuts of meat or trim off excess fat. Rather, controlling carbs is what's important."
"The Atkins Diet holds that eating too many carbs - especially sugar, white flour and other refined carbs - leads to many issues. The Atkins Diet says that it leads to blood sugar imbalances, weight gain and heart problems. To that end, the Atkins Diet limits carbs. The Atkins Diet encourages eating more protein and fat. But the Atkins Diet says it's not a high-protein diet."
"Like many diet plans, the Atkins Diet keeps changing. It now encourages eating more high-fiber vegetables and has included changes to meet vegetarian and vegan needs."
"Most people can lose weight on almost any diet plan that restricts calories - at least in the short term. Over the long term, though, studies show that low-carb diets like the Atkins Diet are no more effective for weight loss than are standard weight-loss diets. And studies find that most people regain the weight they lost no matter which diet plan they used."
"...the main reason for weight loss on the Atkins Diet is lower overall calorie intake from eating less carbs. Some studies suggest that there are other reasons for weight loss with the Atkins Diet. You may shed pounds because your food choices are limited. And you eat less since the extra protein and fat keep you feeling full longer."
"The Atkins Diet says that its eating plan can prevent or improve serious health conditions, such as metabolic syndrome, diabetes, high blood pressure and heart disease. In fact, almost any diet that helps you shed excess weight can reduce or even reverse risk factors for heart disease and diabetes."
"One study showed that people who followed the Atkins Diet had improved triglycerides, suggesting better heart health. But there have been no major studies to show whether such benefits hold up for the long term or increase how long you live."
"Some health experts believe that eating a large amount of fat and protein from animal sources, as allowed on the Atkins Diet, can increase your risk of heart disease or some cancers. But it's not known what risks, if any, the Atkins Diet may pose over the long term because most of the studies about it have lasted for two years or less."
"The Atkins Diet says that cutting carbs extremely in the early phase of the program can cause some side effects..." (These include dizziness, weakness, fatigue, and constipation.)
"Some very low-carb diets also restrict carbs so much that they cause you not to have enough nutrients or fiber. This can cause such health problems as constipation, diarrhea and nausea. Eating carbs that are high fiber, whole grain and high in nutrients can improve the health profile of programs like the Atkins Diet, though. It's also possible that restricting carbohydrates to less than 20 grams a day - the level recommended for phase 1 of the diet - can result in ketosis."

In a critical commentary on the Atkins diet, Ornish (2004. J Am Diet Assoc. 104(4):537-42) noted that “an Atkins diet is high in disease-promoting substances and low in protective ones,” and “The goal is to lose weight in ways that enhance health rather than in ways that may harm it.”

Blood Type ("Eat Right for Your Type") - popularized by Peter D'Adamo (a naturopath). It proposes that ABO blood types reflect different genetic heritages which should lead to different optimum diets, avoiding reactions of lectins with blood cells. "Based on the ‘Blood-Type’ diet theory, group O is considered the ancestral blood group in humans so their optimal diet should resemble the high animal protein diets typical of the hunter-gatherer era. In contrast, those with group A should thrive on a vegetarian diet as this blood group was believed to have evolved when humans settled down into agrarian societies. Following the same rationale, individuals with blood group B are considered to benefit from consumption of dairy products because this blood group was believed to originate in nomadic tribes. Finally, individuals with an AB blood group are believed to benefit from a diet that is intermediate to those proposed for group A and group B. The ‘Blood-Type’ diet also proposes that lectins, which are sugar-binding proteins found in certain foods, could cause agglutination if they are not compatible with an individual's ABO blood group" (Wang et al. 2014. PLoS One. 9(1):e84749).

Reviews:

Cusack et al. 2013. Am J Clin Nutr. 98(1):99-104: "No evidence currently exists to validate the purported health benefits of blood type diets."
Wang et al. 2014. Op. cit.: "Adherence to certain 'Blood-Type' diets is associated with favorable effects on some cardiometabolic risk factors, but these associations were independent of an individual's ABO genotype, so the findings do not support the 'Blood-Type' diet hypothesis."

Notes: Biochemical and evolutionary premises are absurd. Reshanov (2014 Jan 20. EarthSky) wrote, "So what gives the blood-type diet its appeal? Personally, I suspect it’s because there’s something genuinely enjoyable about grouping things into categories. It’s like taking one of those 'which Harry Potter character are you?' quizzes online. Each of the blood types even come with their own astrology-esque personality traits. And the list of recommended/to-be-avoided foods used for the study is itself hours of fun. Interestingly, everyone can have broccoli and kale, but nobody can have olives...Entertainment value aside, the diets themselves aren’t terrible. The Type A diet, for one, looks like the standard plant-based, whole-grain affair often recommended for those at risk for cardiovascular disease. And the other diets are reasonable enough too, and certainly an improvement on many modern eating habits. There is no blood group for which D’Adamo recommends a regimen of 32-ounce sodas and chocolate-frosted pop-tarts...So if you currently subsist primarily on junk food, as often the case, and you can stick to one of these diets, then, sure, you may indeed lose weight and feel better. But it likely has nothing to do with your blood type."

Blue Zones Diet - here the aim is to promote longevity. “The so-called Blue Zones are geographical locations where people are said to live longer than elsewhere...The Blue Zone Diet assumes that common dietary factors have been identified and that following the diet will make us live longer. That appears to be a false assumption based on speculation, misinformation, and wishful thinking, not on science...The claims of longevity in those locations may be based on fraud and error...The Blue Zone Diet essentially repeats much of the conventional advice for a healthy diet: A diet similar to the Mediterranean diet, with whole grains, fruits, vegetables, nuts, legumes, seeds, and spices, with meat consumed sporadically, mainly fish and lean meat...If you follow these Blue Zone guidelines, will you live longer? Maybe. We simply don’t know yet. Good controlled studies are lacking, and time will tell. Humans live a long time, so the effect of this diet won’t be measurable until many years have passed” (Hall 2021 Oct 12. Blue Zones Diet: speculation based on misinformation. Science-Based Medicine blog).

DASH (Dietary Approach to Stop Hypertension) - "The DASH diet is a healthy-eating plan designed to help treat or prevent high blood pressure (hypertension). The DASH diet includes foods that are rich in potassium, calcium and magnesium. These nutrients help control blood pressure. The diet limits foods that are high in sodium, saturated fat and added sugars. Studies have shown that the DASH diet can lower blood pressure in as little as two weeks. The diet can also lower low-density lipoprotein (LDL or 'bad) cholesterol levels in the blood...The DASH diet is lower in sodium than a typical American diet, which can include a whopping 3,400 milligrams (mg) of sodium or more a day. he standard DASH diet limits sodium to 2,300 mg a day...A lower sodium version of DASH restricts sodium to 1,500 mg a day...The DASH diet is rich in vegetables, fruits and whole grains. It includes fat-free or low-fat dairy products, fish, poultry, beans and nuts. It limits foods that are high in saturated fat, such as fatty meats and full-fat dairy products" (Mayo Clinic 2021. DASH diet: Healthy eating to lower your blood pressure).

"Detox" or "cleansing" - the aim may be to remove the body of alleged "toxins" rather than to lose weight. The general ideas behind "detox" diets are unscientific and are discussed in the article "Chelation therapy; allergy and arthritis treatments; other miscellaneous topics" (CHELATION AND MISC). "Like other fad diets, detox regimens promise quick weight losses that are ultimately unsustainable" (Sine 2006. Detox diets: purging the myths. WebMD).

Fasting - see intermittent fasting

Fat burners - see thermogenic supplements

Food Combining - the following points were made by Jones (2021. Does food combining work? Healthline):

"Proponents of food-combining diets believe that improper food combinations can lead to disease, toxin buildup, and digestive issues. They also believe that proper combinations can actually help relieve these problems."
"Food-combining principles first appeared in the Ayurvedic medicine of ancient India, but they became more widely popularized in the mid-1800s under the term 'trophology,' or 'the science of food combining.' The principles of food combining were revived in the early 1900s by the Hay diet. Since then, food combining has become a popular practice supported by some in the health and wellness world."
"Generally, food-combining diets assign foods to different groups. These are usually broken down into carbs and starches, fruits (including sweet fruits, acidic fruits, and melons), vegetables, proteins, and fats. Alternatively, some plans classify foods as acidic, alkaline, or neutral."
"The laws of food combining can vary somewhat depending on the source, but the most common rules are: Eat fruit only on an empty stomach, especially melons. Avoid combining starches and proteins. Avoid combining starches with acidic foods. Avoid combining different types of protein. Consume dairy products only on an empty stomach, especially milk. Other rules say that protein should not be mixed with fat, sugar should only be eaten alone, and fruits and vegetables should be eaten separately."
"In fact, there is no evidence to support most of the principles of food combining. What’s more, many of the original food-combining diets were developed more than 100 years ago, when much less was known about nutrition and digestion. What we now know about basic biochemistry and nutritional science directly contradicts most of the principles of food combining."
"The term 'mixed meals' refers to meals that contain a combination of fat, carbs, and protein. The rules of food combining are largely based on the idea that the body is not equipped to digest mixed meals. However, this is not the case, as the human body evolved on a diet of whole foods, which almost always contain some combination of carbs, protein, and fat."
"Another theory behind food combining is that eating the wrong foods together can hinder digestion by creating the wrong pH for certain enzymes to function...However, eating foods that are more alkaline or acidic does not significantly change the pH of your digestive tract, and your body has several ways of keeping the pH of each part of your digestive tract within the correct range."
"One of the most common supposed effects of improper food combining is that food ferments or putrefies in your stomach. Supposedly, when a fast-digesting food is combined with a slow-digesting food, the fast-digesting food stays in your stomach so long that it begins to ferment. However, this does not happen. Fermentation and rotting occur when microorganisms start to digest your food. But... your stomach maintains such an acidic pH that almost no bacteria can survive."
"SUMMARY: There is no evidence that the practice of food combining offers any benefits. In fact, modern science directly contradicts many of its principles."

Genetically modified organisms (GMOs) - some people feel that it is important to avoid foods containing GMOs, for various reasons. Gavura (2021 May 27. Science-Based Medicine blog) wrote, "Not many individual foods are GMOs, but GMOs do end up in a lot of commercially-prepared food. The FDA has a helpful page that on GMO crops that notes that GMOs may be ingredients in many of the foods we eat, such as corn starch, corn syrup, canola oil, granulated sugar, and soybean oil. There are a small number of fruits and vegetables that can be purchased that are GMO, such as potatoes, summer squash, apples and papayas. Despite the relatively small number of GMO foods, many products are labelled 'non-GMO,' even when there has never been a GMO version available (e.g., rolled oats)...Despite statements made by manufacturers of GMO-free products, there is no credible evidence to substantiate claims that GMO foods increase the risk of bowel hypersensitivity and inflammation of the intestines. Over 1,300 regulatory assessments of GMO crops from around the world have concluded that GMO crops are as safe as their conventional counterparts. Consumers may have different reasons for not wanting to purchase GMO-free foods, but fears about the potential for negative effects of GMOs on the gastrointestinal tract are unfounded."

Gluten-free - "Gluten is a protein composite consisting of gliadins and glutenins, and is found in foods processed from wheat and related grains such as barley and rye" (Gaesser and Angadi 2012. J Acad Nutr Diet. 112(9):1330-3). Individuals with celiac disease need to be on a gluten-free diet. In addition, there is a controversial diagnosis of non–celiac gluten sensitivity, leading to these individuals also seeking gluten-free diets. However, blinded test revealed that some of them did not actually have gluten sensitivity. A study by Boyer et al. (2019. Am J Gastroenterol. 114(5):786-91) found that among naturopathic, integrative medicine, or other alternative medicine practices, a high proportion made claims concerning celiac disease, non-celiac gluten sensitivity, and gluten-free diets. 60% of the marketing claims made by these clinics "were either false or unproven."

Reilly (2016. J Pediatr. 175:206-10) made the following points:

"According to market research, consumers without CD [celiac disease] purchase the vast bulk of gluten-free products."
"According to a 2015 survey of more than 1500 American adults, 'no reason' (35%) was the most common explanation for selecting gluten-free foods, followed by 'healthier option' (26%), and 'digestive health' (19%). 'Someone in my family has a gluten sensitivity' (10%) was more common than those reporting, 'I have a gluten sensitivity,' which was the least common rationale cited (8%)."
"Parents sometimes place their children on a GFD in the belief that it relieves symptoms, can prevent CD, or is a healthy alternative without previous testing for CD or consultation with a dietitian."
"An estimated 0.5% of individuals living in the US adhere strictly to a GFD [gluten-free diet], although a far greater proportion of the population gravitates towards gluten-free foods to more variable degrees."
"The gluten-free industry enjoyed a growth of 136% from 2013 to 2015, reaching estimated sales of $11.6 billion in 20158, far outpacing CD awareness and increases in prevalence."
"For individuals who do not have CD, wheat allergy, or NCGS [nonceliac gluten sensitivity], the latter which has been described in adults but for which there is little evidence in children, there are no data supporting the presumed health benefits of a GFD."
"Gluten-free packaged foods frequently contain a greater density of fat and sugar than their gluten-containing counterparts. Increased fat and calorie intake have been identified in individuals after a GFD. Obesity, overweight, and new-onset insulin resistance and metabolic syndrome have been identified after initiation of a GFD. A GFD also may lead to deficiencies in B vitamins, folate, and iron, given a lack of nutrient fortification of many gluten-free products."
"There also are noteworthy non-nutritional implications of a GFD. Worldwide, those purchasing gluten-free products will encounter far greater food costs than gluten containing competitors. Social isolation and inconvenience have been reported by children with CD requiring a GFD, and some with CD report a deterioration in their quality of life while on a GFD, linked in many cases to the diet itself."
"There are no data to support the theory of an intrinsically toxic property of gluten for otherwise-healthy and asymptomatic adults and children, and certain studies have specifically demonstrated a lack of toxic effect."
"A minority of those with gluten related symptoms are wheat allergic...Wheat allergic individuals typically may safely consume other gluten-containing foods without issue following specific exclusion of wheat."
"There is arguably no role for a GFD for children outside of treatment of CD and wheat allergy...Certainly there is no evidence to support a GFD for asymptomatic children without CD, or for delaying gluten introduction to infants to prevent CD."

Among the points made by Gaesser and Angadi (2012. Op. cit.):

"Gluten-free diets have also been used by patients with autism spectrum disorders (ASD). However, there are no definitive data to support the use of gluten-free diets in ASD, and the American Academy of Pediatrics does not support the use of gluten-free diets as a primary treatment for individuals with ASD."
"Naturally occurring fructan-type resistant starches in wheat, such as oligofructose and inulin, are beneficial for creating a healthy composition of gut bacteria, and these diet–microbe interactions in the colon may protect the gut from some cancers, inflammatory conditions, and cardiovascular disease. By removing the major source (wheat) of fructan-type resistant starches in American diets, strict adherence to a gluten-free diet could have adverse consequences. In fact, recent evidence suggests that a gluten-free diet may lead to reductions in beneficial gut bacteria."
"Despite numerous health claims and the exploding popularity of gluten-free products, there are no published data to support a weight loss claim for a gluten-free diet...Gluten-free baked goods can be high in fat and total energy. Moreover, whole-grain intake is inversely associated with BMI, and wheat is the most widely consumed grain in America. Thus, going gluten-free for purposes of weight loss may have unintended consequences."

Fasano (2015 Dec 18. Five myths about gluten. Washington Post) wrote, "The fact that about 1 percent of the population is affected by celiac disease, while almost 100 percent of humankind is exposed to gluten-containing grains, is evidence that these grains are safe for most people. After all, our species has evolved during the past 10,000 years eating gluten-containing grains."

Hallelujah - a vegan, "biblically based" diet with natural foods and supplements. Developed by Rev. George Malkmus. Allegedly can reverse over 170 diseases. Barrett (2003. Rev. George Malkmus and his Hallelujah Diet. Quackwatch) wrote, "Although low-fat, high-fiber diets can be healthful, the Hallelujah Diet is unbalanced and can lead to serious deficiencies. The overall program is expensive because the recommended supplements cost over $2,000 a year. Reverend Malkmus’ sales pitch includes beliefs that are historically and nutritionally senseless, as well as health claims for which he lacks appropriate substantiation. Using his diet instead of appropriate medical care is very foolish."

Intermittent fasting - "IF comes in three main flavors: alternate-day fasting, when people alternate between feast days (eating normally or a little extra) and fast days with one meager meal of about 500 calories; the 5:2 plan, which means eating normally five days a week but only one scant meal the other two days; and time-restricted eating, when daily dining is confined to a window of eight hours (or, in some versions, six or 10 hours)" (Wallis 2020 Sep 1. How good a diet is intermittent fasting? Scientific American). It is thought that intermittent fasting depletes glycogen, leading to reliance on ketones for energy, which results in further metabolic changes. One of these is autophagy, in which damaged proteins are destroyed. Another proposal is that the fasting provokes beneficial stress responses. Intermittent fasting may provide some benefits of standard calorie restriction but be easier to comply with. Benefits are supported by some animal studies and some human trials. A recent trial with 139 participants found that "time-restricted eating was not more beneficial with regard to reduction in body weight, body fat, or metabolic risk factors than daily calorie restriction" (Liu et al. 2022. N Engl J Med. 386(16):1495-1504).

Ketogenic - see also low carbohydrate. "The ketogenic diet, or keto diet, emerged in popularity after a recent series of other low-carbohydrate diets, such as the Paleo and Atkins diets. The ketogenic diet is unique from other low-carbohydrate diets in that followers of the diet are encouraged to forgo nearly all carbohydrates, avoid excess protein, and consume high levels of fat (generally exceeding 70% of calories consumed), resulting in the production of ketones, giving the diet its name" (Joshi et al. 2019. JAMA Intern Med. 179(9):1163-4). "Ketones" here refers to acetoacetate and beta-hydroxybutyrate, formed from fat by the liver as a source of energy for other tissues, as well as acetone, formed by nonenzymatic breakdown of acetoacetate.

Joshi et al. (op. cit.) made the following points:

"Is the ketogenic diet more effective for weight loss than other diets? In a meta-analysis of 13 studies lasting longer than a year, researchers found that the ketogenic diet was associated with less than a kilogram of additional weight loss over high-carbohydrate, low-fat strategies. This difference, although statistically significant, may not be clinically significant. Furthermore, a meta-analysis of 32 controlled feeding studies found that energy expenditure and fat loss were greater with low-fat diets compared with ketogenic diets."
"A review of the literature on ketogenic diets for the treatment of pediatric epilepsy reveals multiple adverse effects, ranging from the relatively benign but inconvenient 'keto flu,' an induction period of fatigue, weakness, and gastrointestinal disturbances, to the less common but deadlier occurrence of cardiac arrhythmias from selenium deficiency. Other documented adverse effects include nephrolithiasis, constipation, halitosis, muscle cramps, headaches, diarrhea, restricted growth, bone fractures, pancreatitis, and multiple vitamin and mineral deficiencies."
"The greatest risk, however, of the ketogenic diet may be the one most overlooked: the opportunity cost of not eating high-fiber, unrefined carbohydrates. Whole grains, fruits, and legumes are some of the most health-promoting foods on the planet."

Ernst (2020 Sep 16. "Keto-flu" - a side-effect of a popular diet. Edzard Ernst blog) pointed out that "the diet is quite unpalatable on the long-run and soon puts people off eating. This, of course, might be one mechanism by which KD leads to weight loss."

Low carbohydrate - see also ketogenic diet. Variations include Atkins, ketogenic, Zone, 40-30-30, and South Beach diets. "There are several types of CHO[carbohydrate]-restricted diets, some of which restrict CHO to very low levels without restricting dietary protein and fat (eg, Atkins-style diet), whereas others allow moderate CHO intake with moderate protein and fat intake (eg, South Beach, Zone). Contemporary very-low-CHO diets limit protein to moderate levels to induce ketosis without restricting fat or total calories...a CHO-restricted diet is defined as CHO intake below the lower boundary of the acceptable macronutrient distribution range for healthy adults (45–65% TDE [total daily energy]). A moderate-CHO diet is defined as 26–44% TDE from CHO (130–225 grams CHO/d for a reference 2000 kcal diet), a low-CHO diet as 10–25% TDE from CHO (50–130 grams CHO/d), and a very-low-CHO diet as <10% TDE from CHO (<50 grams CHO/d)" (Kirkpatrick et al. 2019. J Clin Lipidol. 13(5):689-711).

Presumed mechanism of action:

Premises include the idea that carbohydrates cause insulin secretion, leading to storage as fat rather than use for energy; that the rapid increase in insulin causes a drop in blood glucose, leading to hunger and more eating; and that insulin causes production of "bad" eicosanoids, which lead to heart disease, cancer, diabetes, and other problems.
Weight loss could arise from restricted calories and ketosis-induced appetite suppression. There is also a rapid initial weight loss due to reduction in glycogen (and its associated water).
"Several lines of evidence suggest that the higher protein level consumed on low-carbohydrate diets is key in regulating food intake and body weight. It is generally accepted that proteins suppress food intake and are more satiating than fats or carbohydrates and by a greater percentage than can be accounted for by energy content alone...Several mechanisms may explain how protein affects satiety and overall intake. Bioactive peptides activated during protein digestion act on centers within the digestive tract that in turn signal the brain. Free amino acids activate neurochemical systems within the brain to terminate eating as well as to impact macronutrient choice. Also, the end products of protein metabolism (amino acids, ammonia, and urea) signal excess intake and probably play a role in determining meal intervals" (Levine et al. 2006. J Am Diet Assoc. 106(12):2086-94).
"These diets have also been suggested to have health benefits over low fat diets, mainly on the basis of results from short term intervention studies. These benefits include reductions in plasma triglyceride, glycated haemoglobin, and insulin concentrations as well as in systolic blood pressure" (Floegel and Pischon 2012. BMJ. 344:e3801).
Ebbeling et al. (2012. JAMA. 307(24):2627-34), discussing possible differences in energy expenditure with different diets, wrote, "Diets that aim to attenuate the increase in blood glucose levels after eating - specifically, low–glycemic index (emphasizing carbohydrate source) and very low-carbohydrate (focusing on carbohydrate restriction) diets - have been hypothesized to confer such a 'metabolic advantage.' Acutely, reducing dietary glycemic load diet may elicit hormonal changes that improve the availability of metabolic fuels in the late postprandial period, and thereby decrease hunger and voluntary food intake. Chronically, a low–glycemic load diet may attenuate the decline in resting energy expenditure (REE) that occurs during weight loss."

Possible adverse effects: inadequate nutrient intake, constipation, ketosis, kidney problems, and increased cholesterol (with risk of heart disease). Reddy et al. (2002. Am J Kidney Dis. 40(2):265-74) reported that a low carbohydrate, high protein diet for 6 weeks “delivers a marked acid load to the kidney, increases the risk for stone formation, decreases estimated calcium balance, and may increase the risk for bone loss.” "Despite the popularity of these diets, clinicians should probably advise against their use for long term control of body weight. The European Society of Cardiology recommends high intakes of fruits, vegetables, and wholegrain products and reduced fat intake, a pattern unlikely to fit low carbohydrate-high protein diets...the short term benefits of low carbohydrate-high protein diets for weight loss that have made these diets appealing seem irrelevant in the face of increasing evidence of higher morbidity and mortality from cardiovascular diseases in the long term" (Floegel and Pischon 2012. Op. cit.).

Reviews and major trials (see also "Reviews of Multiple Diets" above):

Halton et al. 2006. N Engl J Med. 355(19):1991-2002 [Nurses' Health Study]: "Our findings suggest that diets lower in carbohydrate and higher in protein and fat are not associated with increased risk of coronary heart disease in women. When vegetable sources of fat and protein are chosen, these diets may moderately reduce the risk of coronary heart disease."
Lagiou et al. 2012. BMJ. 344:e4026 [trial with 43,000 Swedish women]: "Low carbohydrate-high protein diets, used on a regular basis and without consideration of the nature of carbohydrates or the source of proteins, are associated with increased risk of cardiovascular disease."
Atallah et al. 2014. Circ Cardiovasc Qual Outcomes. 7(6):815-27: " Head-to-head RCTs [randomized controlled trials], providing the most robust evidence available, demonstrated that Atkins, WW, and Zone achieved modest and similar long-term weight loss. Despite millions of dollars spent on popular commercial diets, data are conflicting and insufficient to identify one popular diet as being more beneficial than the others."
Kirkpatrick et al. 2019. Op. cit.: "Based on the evidence reviewed, low-CHO and very-low-CHO diets are not superior to other dietary approaches for weight loss. These diets may have advantages related to appetite control, triglyceride reduction, and reduction in the use of medication in T2D [type 2 diabetes] management. The evidence reviewed showed mixed effects on low-density lipoprotein cholesterol levels with some studies showing an increase. There was no clear evidence for advantages regarding effects on other cardiometabolic risk markers. Minimal data are available regarding long-term (>2 years) efficacy and safety."

Notes:

A review of insulin and fat metabolism (Schwartz 2000. Science. 289(5487):2066-7) noted: "The pervasive notion that insulin causes obesity...has hindered acceptance of insulin as a signal to the brain that limits weight gain. Although the concept that insulin triggers weight gain has little scientific merit, it remains a key selling point for advocates of diets that are low in carbohydrate and high in protein and fat. It is true that obesity is strongly associated with increased circulating insulin levels (hyperinsulinemia), but this relation is most likely due to obesity-induced insulin resistance, rather than to obesity-promoting effects of insulin, because increased insulin secretion actually protects against subsequent weight gain in obese humans. If hyperinsulinemia has adverse consequences, obesity does not appear to be among them."
The American Heart Association Nutritional Committee issued an advisory (2001. Circulation. 104(15):1869-74) that high protein diets are not supported by evidence of effectiveness, and pose health risks.
In early 2004, the Atkins organization reduced the recommended percentage of fat in the diet to 60% of calories and the amount of saturated fat to 20%. (Some feel that this was in response to the increasingly popular South Beach Diet, which has some similarities to Atkins in the initial two weeks, but then adds back more healthy carbohydrates.)
In a 2004 review, Astrup et al. (2004. Lancet. 364(9437):897-9) wrote, “The success of the low-carbohydrate diet might be due to the restriction of the variety of food choices - the monotony and simplicity of the diet could inhibit appetite and food intake. Also, protein induces a stronger satiating effect than fat and carbohydrate, which would decrease ad-libitum food intake and bodyweight.” However, since the long-term safety has not been demonstrated, they concluded that “low-carbohydrate diets cannot be recommended.”
"Atkins advocated his diet for more than 30 years and stated that more than 60,000 patients treated at his center had used his diet as their primary protocol. However, he never published any study in which people who used his program were monitored over a period of several years. It would not have been difficult for him to compile simple data, but I have seen no evidence that did so" (Barrett 2008. Low-carbohydrate diets. Quackwatch).
"The popularity of low-carbohydrate diets has encouraged food companies to market low-carbohydrate foods for people who want to 'watch their carbs.' Most of these foods are much higher in fat than the foods they are designed to replace. I believe that 'low-carb' advertising is encouraging both dieters and nondieters to eat high-fat foods, which is exactly the opposite of what medical and nutrition authorities have been urging for decades" (Ibid.).
"In a 2018 survey of Americans between 18 and 80 years of age (n = 1009), 16% reported following some type of low-CHO eating pattern in the past year" (Kirkpatrick et al. 2019. Op. cit.).
"Results from meta-analyses indicate that low-CHO and very-low-CHO diets may elicit improvements in TG [triglyceride] and HDL-C [high-density lipoprotein cholesterol] levels, glycemic control, and reductions in diabetes medications, but have variable effects on LDL-C [low-density lipoprotein cholesterol] levels; however, by approximately 2 years, there are no differences for most cardiometabolic risk markers. Moreover, three separate observational studies, including a large prospective cohort study with long-term follow-up, have shown that a very-low-CHO intake is associated with increased all-cause mortality. Evidence also demonstrates that adherence to the severe CHO restriction of very-low-CHO diets is challenging and has the potential to cause adverse side effects. In addition, VLCHF diets challenge the nutrition recommendations of various professional organizations, severely restrict or eliminate foods associated with cardioprotective benefits, and encourage a high intake of foods known to increase ASCVD [atherosclerotic cardiovascular disease] risk (eg, processed meats, foods rich in SFAs [saturated fatty acids]). Long-term studies on the potential impact of ASCVD outcomes are lacking" (Ibid.).

Reviews comparing multiple types of diets (low carbohydrate and others) found similar long-term weight losses, with the intake of calories and adherence to the diets being the major factors.

Macrobiotic - "A macrobiotic diet (or macrobiotics) is a fad diet based on ideas about types of food drawn from Zen Buddhism. The diet tries to balance the supposed yin and yang elements of food and cookware. Major principles of macrobiotic diets are to reduce animal products, eat locally grown foods that are in season, and consume meals in moderation. There is no high-quality clinical evidence that a macrobiotic diet is helpful for people with cancer or other diseases, and it may be harmful. Neither the American Cancer Society nor Cancer Research UK recommends adopting the diet" (Wikipedia 2022. Macrobiotic diet)."The macrobiotic diet is a predominantly vegetarian, whole-foods diet that has been shown to improve serum glucose and lipid levels, and thus reduce total body fat and body mass. Some research indicates the macrobiotic diet may produce favorable changes in immunologic parameters and decrease inflammation in the body" (Leung et al. 2018. Nutr Health. 24(1):11-8). "If you’re looking for a healthy eating plan, the macrobiotic diet is a good choice. It’s rich in nutrient-packed foods that are also low in calories. While there’s no absolute proof, medical research suggests diets that are mostly vegetables, fruits, and whole grains may lower the risk of several diseases, including heart disease and cancer. Either way, you’ll reap plenty of health benefits with this diet. If your goal is to lose weight, the macrobiotic diet will likely do the trick too, but don’t get caught in the carb trap. Many people replace meat with carbs. Starchy carbs, like potatoes, rice, and pasta, are easy to overeat, packing on the calories and the pounds. Instead, reach for veggies in place of meat" (Rogers 2022. Macrobiotic diet. WebMD).

McDougall Program - starch-based diet promoted by John McDougall, MD. Principles are: "1. Follow a diet centered around starches with the addition of fresh or frozen fruits and vegetables. 2. Give up meats, fish, poultry, dairy products, eggs, oils, refined foods, alcohol, and caffeine (except for rare special occasions). Limit fat, sugar, and salt. 3. Exercise every day" (Hall 2020 Oct. 20. The McDougall Diet. Science-Based Medicine blog). Critics find his ideas (such as that dairy food is responsible for numerous disease) to be preposterous. "Some of McDougall’s recommendations are in line with mainstream advice, but there is reason to fear that strict adherence to his whole Program might result in nutritional deficits that could do more harm than good" (Ibid.).

Mediterranean - "The Mediterranean diet is a diet inspired by the eating habits of people who live near the Mediterranean Sea. When initially formulated in the 1960s, it drew on the cuisines of Greece, Italy, France and Spain. In decades since, it has also incorporated other Mediterranean cuisines, such as those in the Balkans, the Middle East, North Africa and Portugal. The principal aspects of this diet include proportionally high consumption of olive oil, legumes, unrefined cereals, fruits, and vegetables, moderate to high consumption of fish, moderate consumption of dairy products (mostly as cheese and yogurt), moderate wine consumption, and low consumption of non-fish meat products. Olive oil has been studied as a potential health factor for reducing all-cause mortality and the risk of chronic diseases. The Mediterranean diet is associated with a reduction in all-cause mortality in observational studies. There is some evidence that the Mediterranean diet lowers the risk of heart disease and early death, although a 2019 review determined that the evidence had low quality and was uncertain. The American Heart Association and American Diabetes Association recommend the Mediterranean diet as a healthy dietary pattern that may reduce the risk of cardiovascular diseases and type 2 diabetes, respectively. The Mediterranean diet may help with weight loss in obese people. The Mediterranean diet is one of three healthy diets recommended in the 2015-2020 Dietary Guidelines for Americans, along with the DASH diet and vegetarian diet" (Wikipedia 2022. Mediterranean diet).

Reviews:

Dinu et al. 2018. Eur J Clin Nutr. 72(1):30-43: "A robust evidence...for a greater adherence to the Mediterranean diet and a reduced the risk of overall mortality, cardiovascular diseases, coronary heart disease, myocardial infarction, overall cancer incidence, neurodegenerative diseases and diabetes was found."
Rees et al. 2019. Cochrane Database Syst Rev. CD009825: "Despite the relatively large number of studies included in this review, there is still some uncertainty regarding the effects of a Mediterranean-style diet on clinical endpoints and CVD [cardiovascular disease] risk factors for both primary and secondary prevention. The quality of evidence for the modest benefits on CVD risk factors in primary prevention is low or moderate, with a small number of studies reporting minimal harms. There is a paucity of evidence for secondary prevention."

NutriMost Fat Loss System - developed by Ray Wisniewski, D.D. "He began franchising it in 2014 and, by January 2016, the program was available through more than 160 clinics, most of which were operated by chiropractors" (Barrett 2022. A close look at the NutriMost Fat Loss System. Chirobase). In the original version, customers purchased a scan using an unscientific device (ZYTO) that allegedly identified the person's top "organ stressors," allowing the formulation of an individualized diet plan. They were then prescribed an extremely low-calorie diet (about 500 calories per day). In 2016-2019 the FTC and several states took action against marketers for making claims that were "deceptive and not supported by scientific evidence."

Barrett (Ibid.) provided an update: "In 2017, NutriMost redesigned its approach along more standard lines, raised the caloric content of its diet program, abandoned use of the ZYTO device, advised clinic operators to stop using abusive contracts, and promised the FTC that any future weight loss and health claims would be supported with competent and reliable scientific evidence. NutriMost’s current program begins with an analysis called 'NutriMost Intelligence,' in which the client receives diet and supplement recommendations based on the answers to questions in an iPad app. A NutriMost official told me that the company plans to conduct an appropriate study of its revised program, but I do not know the details of the program or the proposed study. Whether NutriMost can demonstrate that its program is effective and worth its high cost remains to be seen."

Nutritarian - "Joel Fuhrman, MD is a celebrity doctor, entrepreneur, and best-selling author whose latest book, Eat for Life, advocates his 'Nutritarian' or micronutrient-rich diet" (Hall 2022 Jan 4. Eat for Life: Joel Fuhrman's Nutritarian diet. Science-Based Medicine blog). The diet supposedly "will increase longevity and prevent or treat most chronic diseases...His Nutritarian diet is essentially a new and improved vegan diet...A Nutritarian diet requires a lot of time invested in shopping and chopping and it’s very restrictive. I don’t think most people would find it palatable or would be able follow it long term" (Ibid.).

Ornish - Developed by Dr. Dean Ornish. "The Ornish diet is lacto-ovo vegetarian as it includes non-fat dairy products and egg whites in moderation. On the Ornish diet all meat, fish, poultry, fat dairy products, coconuts, margarine, nuts, seeds, avocadoes, olives, and cooking oils (apart from canola oil) are forbidden. The diet is very low in fat with 10 percent of fat from total calories and low in cholesterol. The Ornish diet emphasises consumption of fruits, legumes, vegetables and whole grains. The diet also recommends the use of fish oil supplements...Critics have stated that Ornish has not provided sufficient clinical evidence to support his claims and his studies have not been replicated. Nutritionists have described the Ornish diet as a high-carbohydrate low-fat fad diet. The Ornish diet can lower blood cholesterol but a criticism is that it restricts fish, nuts and olive oil which may protect against heart disease. Nutritionist Fredrick J. Stare commented that the Ornish diet is too low in fat for most people to follow and it may result in deficiencies of essential fatty acids. Stare noted that although the diet has been shown to stop the progression of arterial blockage in persons with cardiac disease, the diet is unbalanced and too extreme for most people to stick with long-term. Because of the restricted nature of the Ornish diet it has a high discontinuation rate; the American Heart Association and the U.S. Department of Health have not recommended the diet" (Wikipedia 2020. Dean Ornish).

According to Davidson (2008. Dean Ornish's Eat More, Weigh Less. In Longe (ed.). The Gale Encyclopedia of Diets: A Guide to Health and Nutrition. Vol. I. pp. 252–255, as cited by Wikipedia), "Dr. Ornish’s diet is very low in fat and limits meat and animal product intake to little or none. Many important vitamins and minerals such as zinc and vitamin B12 are acquired from these sources in a normal diet. Without these sources there is a significant possibility of deficiency. Also, because of the very low fat allowance of the diet there is some concern that people on this diet may not get enough vitamin E, which is found mainly in nuts and oil...Dr. Ornish often recommends taking supplements while following his diet, and taking a complete multivitamin may help reduce the risk of a deficiency."

"In the US, the Ornish and Pritikin diets are covered under Medicare but only if prescribed for cardiac rehabilitation...The Ornish program has been purported to reverse the progression of conditions such as heart disease, diabetes, and hypertension" (Leung et al. 2018. Nutr Health. 24(1):11-8).

Paleo - "The Paleolithic diet, Paleo diet, caveman diet, or stone-age diet is a modern fad diet consisting of foods thought by its proponents to mirror those eaten by humans during the Paleolithic era. The diet avoids processed food and typically includes vegetables, fruits, nuts, roots, and meat and excludes dairy products, grains, sugar, legumes, processed oils, salt, alcohol, and coffee. Historians can trace the ideas behind the diet to 'primitive' diets advocated in 19th century. In the 1970s Walter L. Voegtlin popularized a meat-centric 'Stone Age' diet; in the 21st century the best-selling books of Loren Cordain popularized the Paleo diet. As of 2019 the paleo-diet industry was worth approximately US$500 million. In the 21st century, the sequencing of the human genome and DNA analysis of the remains of early humans have found evidence that humans evolved rapidly in response to changing diet. This evidence undermines a core premise of the paleolithic diet - that human digestion has remained essentially unchanged over time. Anthropological science has found that human diets in paleolithic times were more varied and less meat-centric than had previously been assumed.

"Advocates promote the paleolithic diet as a way of improving health. There is some evidence that following it may lead to improvements in body composition and metabolism compared with the typical Western diet or compared with diets recommended by some European nutritional guidelines. On the other hand, following the diet can lead to nutritional deficiencies such as an inadequate calcium intake, and side effects can include weakness, diarrhea, and headaches" (Wikipedia 2022. Paleolithic diet).

"This diet can put you at risk for deficiencies in calcium and vitamin D, which are critical to bone health. At the same time, you may consume saturated fat and protein far above recommended levels due to eating so much meat. This can cause an increased risk of kidney and heart disease and certain cancers" (Nella 2022. Paleo diet: What it is and why it's not for everyone. Good Food is Good Medicine blog. UC Davis Health).

An article in WebMD (2021. All about the paleo diet) made the following points:

"In general, you'll try to stick to local, organic, non-GMO products like fruits, vegetables, nuts, and seeds, plus fish and grass-fed beef. This adds up to a diet that's high in protein and fiber, contains an average amount of fat, and is low in carbs."
"A paleo diet may be a lot different than how you eat now. For instance, the meat, fish, and produce you eat should be fresh rather than frozen or canned. Some other foods that are OK are eggs, coconut oil, avocado, olives, and a few root vegetables that are high in nutrients, like sweet potatoes. Small amounts of honey are also allowed."
"You need to stay away from dairy products and cereal grains like wheat and oats. But that's not all. You must steer clear of potatoes and legumes like beans, peanuts, and peas. Also off-limits: refined sugar, salt, and highly processed foods."
"A diet with a lot of fruits and vegetables may lower your chances of getting heart disease, including heart attack and stroke. It's can be a good source of fiber, which can help cut your chances of becoming obese or getting type 2 diabetes. You also get more vitamin A, C, and E."
"Go paleo and you may find it easier to drop extra pounds. The types of food you eat will fill you up and make you feel less hungry throughout the day. More studies are needed to see how the paleo diet stacks up against others in the long run."
"Salt is a no-no on the paleo diet. Studies show that cutting back on sodium can lower blood pressure. Plus, when you give up refined carbs, you also help protect your heart in the long run."
"A paleo diet could help prevent diabetes. If you already have it, the types of foods you'll eat may better control your blood sugar and improve how your body responds to insulin. Some research shows that it helps more than a low-salt, low-fat dairy diet that includes whole grains and legumes."
"The paleo diet favors protein, most of which comes from animal products. If you don't stick to lean cuts of meat, you could take in too much saturated fat. That can lead to heart problems. If you have a health issue like kidney disease and need to watch how much protein you have, a paleo diet may not be safe."
"A paleo diet restricts your carbs to around 23% of your total diet, compared to the 45% to 65% that experts suggest. If you lead an active lifestyle, this extreme decrease in carbs may make you tired."
"Some people find it hard to stick with it for a long time. Many common foods like birthday cake, pizza, or even a peanut butter sandwich aren't allowed...And some foods that are heart-healthy, like whole grains, are off-limits."

Pritikin - "The Pritikin diet is a low-fat, high-fibre diet which forms part of the 'Pritikin Program for Diet and Exercise,' a lifestyle regimen originally created by Nathan Pritikin. The 1979 book describing the diet became a best-seller. The diet is based around low-fat, high-fibre food and limiting red meat, alcohol, and processed food. When it was launched, the diet was considered radical, but its precepts are now considered largely in alignment with mainstream nutritional advice. The Pritikin Diet has been categorized as a fad diet with possible disadvantages including a boring food choice, flatulence, and the risk of feeling too hungry. Gastroenterologist David Hershel Alpers and colleagues described the Pritikin diet as 'nutritionally adequate, but the low fat content makes it unpalatable, and the likelihood of compliance is low'" (Wikipedia 2022. Pritikin diet). "The recommended foods are fruits, vegetables, low-fat dairy, legumes, lean protein, and fish. Items to minimize include oils, refined sugars, salt, and refined grains. The plan recommends avoiding processed meats, foods high in saturated fat and those made with trans fat, organ meats, processed meats, and high-cholesterol foods like eggs" (Pagán 2021. Pritikin diet. WebMD). "In the US, the Ornish and Pritikin diets are covered under Medicare but only if prescribed for cardiac rehabilitation" (Leung et al. 2018. Nutr Health. 24(1):11-8).

"The diet’s emphasis on whole, unprocessed foods, daily exercise, and stress management are all scientifically backed ways to help you lose weight in a safe, slow, and healthy manner. However, it’s very low in fat and restricts a long list of foods, which may be hard to sustain long term and not provide your body with enough fat or protein to function properly...The Pritikin Program is one of the few branded diets with research to back its benefits. Still, most research studies were published between the 1970s and 1990s. However, a few modern research studies are available....Despite these results, all studies took place at the Pritikin Longevity Center, which calls into question whether the Pritikin Program is as effective without access to the health specialists and wellness retreats the center offers" (Healthline 2020. Pritikin diet review: benefits, downsides, and more).

South Beach - "The South Beach Diet is a popular fad diet developed by Arthur Agatston and promoted in a best-selling 2003 book. It emphasizes eating food with a low glycemic index, and categorizes carbohydrates and fats as 'good' or 'bad.' Like other fad diets, it may have elements which are generally recognized as sensible, but it promises benefits not backed by supporting evidence or sound science" (Wikipedia 2022. South Beach Diet).

The Wikipedia article also makes the following points:

"The diet has three stages and gradually increases the proportion of carbohydrate consumed as it progresses while simultaneously decreasing the proportions of fat and protein. It includes a number of recommended foods such as lean meats and vegetables and has a concept of 'good' (mostly monounsaturated) fats. It makes no restriction on calorie intake, includes an exercise program, and is based around taking three main meals and two snacks per day."
"The first stage of the diet aims for rapid weight loss (13 lbs in two weeks). According to the UK's National Health Service (NHS), the severity of the first stage of the diet may result in the loss of some vitamins, minerals and fiber. The NHS reports that dietary restrictions during stage one may cause side effects including 'bad breath, a dry mouth, tiredness, dizziness, insomnia, nausea, and constipation.' Such symptoms would be rectified once the less extreme phases of the diet then began."
"Like other fad diets, the South Beach Diet has been marketed with bold claims that are not supported by evidence and with an unrealistic promise of easy weight loss...Nevertheless, some aspects of the diet correspond with dietary advice which is recognized as sensible: its last two stages are sufficiently nutritious to be considered healthy. Like other high-fat diets, its short-term safety has been established, but its long-term safety has not."
"The diet is promoted as improving risk factors associated with cardiovascular disease, but the effectiveness for improving these risk factors is unclear because no evidence on its effects is available. A trial found no change in weight loss compared to usual care."
"South Beach Diet and other low carbohydrate diets lack dietary fiber. Fiber is generally considered to aid weight loss and to help prevent obesity."
"While the South Beach diet does prohibit foods rich in simple carbohydrates such as white bread, white potatoes and white rice, it does not require dieters to forgo carbohydrates entirely or even measure their intake. Instead, it focuses on the 'glycemic impact' (short term change in blood glucose) of foods."

Time-restricted eating - see intermittent fasting

Zone - see also low carbohydrate. "The Zone diet is a fad diet emphasizing low-carbohydrate consumption. It was created by Barry Sears, an American biochemist...The diet is meant to promote weight loss via reduction in calories consumed and avoid spikes in insulin release, thus supporting the maintenance of insulin sensitivity...The Zone diet proposes that a relatively narrow distribution in the ratio of proteins to carbohydrates, centered at 0.75, is essential to 'balance the insulin to glucagon ratio, which purportedly affects eicosanoid metabolism and ultimately produces a cascade of biological events leading to a reduction in chronic disease risk, enhanced immunity, maximal physical and mental performance, increased longevity and permanent weight loss'" (Wikipedia 2022. Zone diet).

The Wikipedia article also makes the following points:

"The diet advocates eating five times a day, with 3 meals and 2 snacks, and includes eating proteins, carbohydrates – those with a lower glycemic index are considered more favorable, and fats (monounsaturated fats are considered healthier) in a caloric ratio of 30%-40%-30% (fat-carb-pro)."
"The diet falls about midway in the continuum between the USDA-recommended food pyramid which advocates eating grains, vegetables, and fruit and reducing fat, and the high-fat Atkins Diet."
"Like other low-carb diets, the ideas underlying the Zone diet are unproven. As of 2013, there were 'no cross-sectional or longitudinal studies examining the potential health merit of adopting a Zone Diet per se, [and] closely related peer-reviewed findings from scientific research cast strong doubt over the purported benefits of this diet. When properly evaluated, the ideas and arguments of popular low carbohydrate diet books like the Zone rely on poorly controlled, non-peer-reviewed studies, anecdotes and non-science rhetoric'."

"The Zone Diet claims to reduce the inflammation in your body. Dr. Sears proposed inflammation was the reason people gain weight, become sick and age faster. Proponents of the diet claim that once you reduce inflammation, you will lose fat at the fastest rate possible, slow down aging, reduce your risk of chronic disease and improve your performance...Although some research shows the diet may improve your blood values, more research is needed before researchers can say this significantly reduces inflammation in the body. There is also little evidence that supports the Zone Diet’s 40% carb, 30% protein and 30% fat ratio as the optimal ratio for fat loss and health benefits" (Healthline 2017. The Zone Diet: a complete overview).

40-30-30 - a diet with 40% of calories from carbohydrates, 30% from fat, and 30% from protein. See Zone diet.

SUPPLEMENTS FOR WEIGHT LOSS

SOME COMPONENTS OF DIET PRODUCTS

(other than macronutrients) (see also individual items below)

"Currently available food supplements feature several purported mechanisms of action, such as improvement of carbohydrate metabolism, increased lipolysis or energy expenditure, and reduced hunger" (Watanabe et al. 2020. Nutrients. 12(9):2873).

Sun et al. (2016. Molecules. 21(10):1351) described and commented on these categories:

Increase in energy expenditure: "Most anti-obesity products usually regulate body weight through an increase of obligatory energy expenditure. In the human body, the function of brown adipose tissue is to transfer energy from food into heat. Uncoupling protein 1 (also known as thermogenin) in brown adipose tissue plays a key role in thermogenic effect. Therefore, a material capable of upregulating uncoupling protein 1 gene expression could be a potential strategy for achieving an anti-obesity effect by increasing energy expenditure."
Appetite suppressant effect: "There has been a rise in satiety-enhancing products on sale in the food supplement marketplace. The biological mechanisms of appetite and satiety are regulated by a complex interaction of neurological and hormonal signals. Many studies have revealed that some food ingredients could provide satiety enhancing effects and be beneficial for weight control. The mechanism underlying the enhanced satiety includes an increase of noradrenaline level and subsequent activation of sympathetic nervous system activity, leading to an increase in satiety and energy expenditure, suppression of hunger, and also elevation in fat oxidation. A line of evidence indicates that neural signal peptides like serotonin, histamine, dopamine, and their associated receptor activities are associated with satiety regulation."
Lipase inhibitory effect: "One of the promising strategies for treating obesity is to interfere with fat absorption along the gastrointestinal tract directly (without altering the central nervous system)...Pancreatic lipase activity is therefore widely considered as one of the most important indicators for the determination of the anti-obesity potential of natural products. As a key enzyme in dietary triglyceride absorption, pancreatic lipase hydrolyzes triglyceride to monoglyceride and fatty acids."
Regulatory effect on adipocyte differentiation: "Adipocytes play a central role in the maintenance of lipid homeostasis and energy balance. They have a particular large capacity to store triglycerides as well as to release free fatty acids in response to changing energy demands. As adipocyte tissue growth is associated with both the hyperplasia and hypertrophy of adipocytes, this has led to the development of natural products in anti-obesity therapy that specifically target adipogenesis inhibition. Some research has also suggested that adipocyte differentiation could be inhibited by the blockade of several transcription factors such as C/EBPβ (CCAAT/enhancer binding protein beta) and PPARγ (peroxisome proliferator-activated receptor gamma)."
Regulatory effect on lipid metabolism: "An increase in the rate of lipolysis stimulates triglyceride hydrolysis and hence diminishes fat storage and combats obesity. The key points to enhance lipolysis have been discussed in many studies. For instance, activation of β-adrenergic receptor initiatively triggered lipolysis in white adipocytes and non-shivering thermogenesis in brown fat. An activation of adenosine monophosphate-activated protein kinase (AMPK) leading to the increase of fatty acid oxidation and glucose transport in skeletal muscle was another example. Hence, transcription factors that can simulate lipolysis become an important feature in the development of anti-obesity products."

"Following the restriction of ephedra use, similar chemical analogs such as synephrine from bitter orange extract became widely accepted replacements. β2-adrenergic receptor agonists work to increase cAMP biosynthesis, while caffeine inhibits the breakdown of cAMP by PDE [phosphodiesterase]. Additionally, salicylates inhibit prostaglandins further allowing the accumulation of cAMP. Taken together, caffeine, β2-adrenergic receptor agonists and salicylates function to synergistically increase cAMP accumulation and metabolic rate" (Vaughan et al. 2014. ISRN Nutr. 2014:650264).

REVIEWS OF MULTIPLE PRODUCTS

Watanabe et al. (2020. Nutrients. 12(9):2873 Op. cit.): "None of the selected dietary supplements were considered to be supported by high-quality evidence, eight of them (green tea, white kidney bean, caffeine, bitter orange, diacylglycerol, resveratrol, grapefruit, chromium) were considered to be supported by moderate-quality evidence, while the other thirteen were considered of low-quality evidence."
Maunder et al. 2020. Diabetes Obes Metab. 22(6):891-903 [herbal medicines]: "As a single agent, only Phaseolus vulgaris resulted in a statistically significant weight loss compared to placebo, although this was not considered clinically significant. No effect was seen for Camellia sinensis or Garcinia cambogia...There is currently insufficient evidence to recommend any of the herbal medicines for weight loss included in the present review."
Bessell et al. 2021. Int J Obes.45(8):1631-43: "Statistically significant weight differences compared to placebo were observed for chitosan...glucomannan...and conjugated linoleic acid...None met our threshold for clinical significance (≥2.5 kg). There was no statistically significant effect on weight for fructans compared to placebo (p = 0.24)...Conclusions: While some dietary supplements containing isolated organic compounds warrant further investigation to determine efficacy and safety, there is currently insufficient evidence to recommend any of these dietary supplements for weight loss."
Lua et al. 2021. J Evid Based Integr Med. 26:2515690X211043738: “Their results suggested that spirulina, chitosan, probiotic, EPA + DHA, vitamin D, fiber, and herbal extract supplementation may all provide small reductions in body weight (ranging from 1-10 kg)...Nonetheless, the evidence is still relatively limited and not encouraging to provide a definitive conclusion due to the methodological shortcomings and the presence of adverse events in chitosan and fiber supplementation.”

CRITIQUES OF WEIGHT LOSS SUPPLEMENTS

"Surprisingly, many dietary supplements advertise one or multiple nonbiased studies illustrating efficacy of their product; however often times these studies have not been systematically peer-reviewed or readily shared with the scientific community making the original research difficult to locate. In addition, identification and tracking of adverse events with the majority of studies would not meet requirements for similar pharmaceutical agents" (Vaughan et al. 2014. ISRN Nutr. 2014:650264).

"Despite significant increases in resting energy expenditure, it is doubtful that commercially available thermogenic products stimulate metabolism more than consumption of food products containing equivocal content of caffeine/stimulants and/or polyphenols. Moreover, it should be mentioned that increases in metabolism induced by food or dietary supplement are small, contributing only subtly to metabolic rate" (Ibid.).

“To make it easier to spot false weight loss representations - the ‘gut check’ claims - the FTC has compiled a list of seven statements in ads that experts say simply can’t be true. If you spot one of these claims in an ad a marketer wants to run in your media outlet, it’s likely to be a tip-off to deception” (FTC 2014. Gut check: A reference guide for media on spotting false weight loss claims). The following are the points made in this document:

“CLAIM #1: Causes weight loss of two pounds or more a week for a month or more without dieting or exercise. Gut check. Meaningful weight loss requires taking in fewer calories than you use. It’s that simple. But it’s also that difficult for people trying to shed pounds. That means ads promising substantial weight loss without diet or exercise are false. And ads suggesting that users can lose weight fast without changing their lifestyles – even without mentioning a specific amount of weight or length of time – are false, too. Some ads might try a subtler approach, say, by referring to change in dress size or lost inches, but the effect is the same.”
“CLAIM #2: Causes substantial weight loss no matter what or how much the consumer eats. Gut check. It’s impossible to eat unlimited amounts of food – any kind of food – and still lose weight. It’s a matter of science: To lose weight, you have to burn more calories than you take in. To achieve success, dieters have to put the brakes on at the dinner table. If an ad says users can eat any amount of any kind of food they want and still lose weight, the claim is false.”
“CLAIM #3: Causes permanent weight loss even after the consumer stops using product. Gut check. Without long-term lifestyle changes – like continuing to make sensible food choices and upping the activity level – weight loss won’t last once consumers stop using the product. Even if dieters succeed in dropping pounds, maintaining weight loss requires lifelong effort.”
“CLAIM #4: Blocks the absorption of fat or calories to enable consumers to lose substantial weight. Gut check. Without lifestyle changes, no over-the-counter product can block enough fat or calories to cause the loss of lots of weight. To work, even legitimate ‘fat blockers’ must be used with a reduced-calorie diet.”
“CLAIM #5: Safely enables consumers to lose more than three pounds per week for more than four weeks. Gut check. Medical experts agree: Losing more than three pounds a week over multiple weeks can result in gallstones and other health complications. So if an ad says dieters can safely and quickly lose a dramatic amount of weight on their own, it’s false.”
“CLAIM #6: Causes substantial weight loss for all users. Gut check. People’s metabolisms and lifestyles are different. So is how they’ll respond to any particular weight loss product. The upshot: No product will cause every user to drop a substantial amount of weight.”
“CLAIM #7: Causes substantial weight loss by wearing a product on the body or rubbing it into the skin. Gut check. Weight loss is an internal metabolic process. Nothing you wear or apply to the skin can cause substantial weight loss. So weight loss claims for patches, creams, lotions, wraps, body belts, earrings, and the like are false. There’s simply no way products like that can live up to what the ads say.”

Sharpe et al. (2006. J Am Diet Assoc. 106(12):2045-51) examined weight loss supplements for sale in 73 stores in South Carolina. They identified 402 products containing 4053 separate ingredients, with an average of 10 ingredients per product.

ADVERSE EFFECTS

Philips and Augustine (2018. J Clin Exp Hepatol. 8(4):471-3) wrote, concerning liver injury due to weight loss supplements, that in most cases it "was found to be due to an active metabolite of the disclosed main ingredient where as in other cases, it was related to undisclosed extracts, adulterants, heavy metals, bacterial contaminants and chemical toxins."

Eichner et al. (2016. J Am Pharm Assoc. 56(5):538-43) obtained 51 weight loss supplement products near Denver, CO. " At least one banned ingredient was found to be listed on the product labels in 17 of the 51 studied supplements (33%). At least one discouraged-use ingredient was found in 46 of the 51 products (90%)." They made the following points concerning banned and dangerous ingredients:

"Although these ingredients have been banned because of cardiovascular, nervous system, and psychiatric issues, many supplements containing these substances are still on the market today. Additionally, there are many other dangerous ingredients that are not banned yet are worthy of caution and education before consumption. Dangerous ingredients include those that are structurally similar to, and produce stimulant effects mimicking, illegal substances such as methamphetamine or highly controlled pharmaceutical amphetamines...These effects, in combination with other stimulants commonly found in weight loss supplements, can act synergistically and amplify an already dangerous response. Additionally, the concern multiplies when combining comorbidities and prescription medications with weight loss dietary supplements."
"A prime example is when picking up many prescription medications, patients are often counseled to avoid grapefruit juice owing to the inhibitory effects on the metabolism of medication. This interaction is common for drugs and ingredients metabolized by enzymes of the cytochrome P450 family, including amphetamines, cyclosporine, and some calcium channel blockers. This effect is caused by the natural component of grapefruit, 6,7-dihydroxybergamottin. This ingredient has been intentionally added to weight loss supplements to amplify the stimulant effect responsible for weight loss. When combined with prescription medications, 6,7-dihydroxybergamottin can result in dangerous side effects potentiated by toxic drug levels."
"Combining ephedra with other ingredients that may contribute to cardiovascular effects can greatly increase the risk of serious adverse events and mortality. These ingredients include synephrine, yohimbine, phenylethylamine (PEA), BMPEA, caffeine, guarana, and DMAA, all of which are readily found in weight loss dietary supplements."
"It is prudent to consider the events that may occur when combining weight loss dietary supplements with prescription medications or common chronic diseases, including heart disease, diabetes, preexisting arrhythmias, and other comorbidities. Consumers may think that they are benefiting their health by using these supplements to lose weight, but in reality they could be disturbing an already serious health condition."
"It is important for consumers to recognize dangerous ingredients in weight loss supplements. Unfortunately, this can be difficult when manufacturers use various names for the same ingredients in an attempt to camouflage the easily recognized substances. Caffeine, for example, is also known by its scientific name 1,3,7-trimethylxanthine, which is often seen on product labels to replace its easily identified name. This is deceiving to consumers who may think that they are purchasing a caffeine-free supplement. In addition, Acacia rigidula extract is often seen on product labels instead of listing the presence of PEA...Because of the small amount of PEA found in naturally occurring A. rigidula, it is almost impossible to achieve the high concentrations of BMPEA and PEA found in these weight loss supplements if only this extract is used."

Mullin (2015. Nutr Clin Pract. 30(3):446-9) wrote, "Ephedra is probably the most effective supplement for weight loss that should never be taken under any circumstances. There's almost no question it will help you lose weight. Of all the supplements my colleagues and I recently examined in a systematic review of the existing weight loss supplements on the market, ephedra had the strongest evidence for efficacy. There's only one problem, and it's a big one: This supplement may kill you...taking ephedra led to a 200%–400% increase in psychiatric, autonomic, and gastrointestinal (GI) problems, as well as heart palpitations. The U.S. Food and Drug Administration (FDA) outlawed the sale of ephedra in 2004."

Mathon et al. (2014. Food Addit Contam Part A Chem Anal Control Expo Risk Assess. 31(1):15-20) surveyed 52 weight loss supplements found on the Internet, and found that half were adulterated with sibutramine, an unsafe drug withdrawn in the U.S. and Europe in 2010.

ALPHABETICAL LISTING OF INDIVIDUAL WEIGHT LOSS SUPPLEMENTS

Abbreviations:

AMPK = AMP-activated protein kinase

BMI = body mass index

BP = blood pressure

CVD = cardiovascular disease

FBG = fasting blood glucose

FTC = Federal Trade Commission

GLP-1 = glucagon-like peptide-1

GLUT4 = glucose transporter 4 (insulin-regulated)

HbA1c = hemoglobin A1c

HDL = high-density lipoprotein

5-HT2c receptor = 5-hydroxytryptamine (serotonin) receptor type 2c

LDL = low-density lipoprotein

MetS = metabolic syndrome

PFM = percentage of fat mass

PI3K = phosphoinositide 3-kinase

PPARα/PGC-1a = peroxisome proliferator activated receptor-alpha/PPAR-gamma coactivator-1α

PPAR-γ = peroxisome proliferator-activated receptor gamma

PYY = peptide YY

RCT = randomized controlled trial

SCFAs = short-chain fatty acids

SIRT-1 = sirtuin 1

SNS = sympathetic nervous system

TAG = triacylglycerol

T2D = type 2 diabetes

UCP-1, UCP-2 = uncoupling protein 1, uncoupling protein 2

WC = waist circumference

WHR = waist-hip ratio

WW = Weight Watchers

Acai - acai berry is the fruit of the acai palm tree.

Notes: "There's no definitive scientific evidence based on studies in people to support the use of acai for any health-related purpose. No independent studies have been published in peer-reviewed journals that substantiate claims that acai alone promotes rapid weight loss. When investigating the safety profile of an acai-fortified juice in rats, researchers found no differences in body weight changes between animals given the juice and animals not given the juice...The Federal Trade Commission has taken action against companies that marketed acai weight-loss products in allegedly deceptive ways" (National Center for Complementary and Integrative Health 2020. Acai).

Agar - "a gelatinous substance extracted from a type of red algae, agarophytes; it is a fiber-rich mixture of natural polysaccharides, mainly agarose and agaropectin" (Watanabe et al. 2020. Nutrients. 12:2873).

Presumed mechanism of action: delayed gastric emptying and increased sense of satiety

Notes: "Overall, the quality of evidence supporting the use of agar for weight loss is low, given the absence of well-designed studies in normoglycaemic obese patients and the paucity of data regarding weight loss in patients with alterations in glucose metabolism. Although current evidence is consistent with other studies that analyzed weight loss with soluble fiber rich diets, suggesting a possible positive effect of agar on weight reduction, there is not enough evidence to recommend its use for this purpose" (Watanabe et al. 2020. Nutrients. 12:2873).

Akavar 20/50

Presumed mechanism of action: "Akavar 20/50 allegedly works in two ways: by delaying the gastric emptying process, and altering levels of 'ghrelin,' the so-called hunger hormone" (Gibb 2007 Jun 25. Akavar 20/50: If it's so good, where's the proof? LawyersandSettlements.com).

Notes: "It contains a long list of ingredients, including large amounts of caffeine from yerba mate, guarana, green tea, and kola nut extracts. It also contains damiana, ginger, schisandra, scutellaria, vitamin B6, magnesium, and other ingredients. Some research suggests that a few of these ingredients might help for weight loss, but this is preliminary. There is no proof that this specific combination of ingredients is effective. Product advertising says, ‘Eat all you want and still lose weight…’ Remind patients that if it sounds too good to be true, it probably is" (Natural Medicines Comprehensive Database newsletter, as quoted by Hall 2008 Jan 22. Science-Based Medicine blog).

Aloe vera

Presumed mechanism of action: "In human studies, A. Vera supplementation was able to decrease serum triglycerides, total cholesterol, LDL, and fasting blood glucose level, as well as reducing HbA1c and insulin levels. These effects on glucose metabolism are thought to be ascribable to acemannan, a mucopolysaccharide contained in A. Vera leaves, which is degraded by the intestinal microbiota to form oligosaccharides capable of inhibiting intestinal glucose absorption; other properties of this plant, seen in animal studies, that may contribute to its positive effect on the lipid and glucose profile are represented by its ability to reduce oxidative stress, activate PPAR transcription, stimulate hepatic lipoprotein activity, and finally also activate hormone-sensitive lipase. Furthermore, many active compounds present in this plant, such as acemannan and polyphenols, may increase the gut microbiota SCFAs production and stimulate gut anorexigenic hormones release, with the effect of reducing food intake and inducing weight loss" (Watanabe et al. 2020. Nutrients. 12:2873).

Possible adverse effects: intestinal cramps, diarrhea. May lower blood glucose so caution is needed for individuals with diabetes. May lower potassium.

Notes: "A. vera has been shown to exert positive effects on glucose and lipid metabolism in both diabetic and nondiabetic patients. Evidence supporting its ability to induce weight loss, however, is limited and of low quality, so its consumption cannot be recommended for this purpose" (Ibid.).

Alpha lipoic acid - see lipoic acid

Artificial sweeteners - "The most common artificial sweeteners fall into three categories:

Non-nutritive natural sweeteners, such as stevia or monk fruit.
Non-nutritive artificial sweeteners, such as saccharin, aspartame, ace K, sucralose, etc.
Sugar alcohols, such as erythritol, xylitol, etc." (Solokas (2021 May 21. Artificial sweeteners - a free lunch, or an obesogenic carcinogen? What 80+ studies say (part 1). Science-Based Medicine blog).

Solokas (Ibid.) made the following points:

"While mis-interpretation of observational studies casts artificial sweeteners in an unfavorable light, to date, there are ZERO well controlled, experimental studies that show a causal link between artificial sweeteners and weight gain."
"...the observational links between artificial sweetener intake and weight gain that the media loves to promote can largely be explained by mistaking correlation for causation and the failure to recognize reverse causality. In other words, people who are gaining weight or already heavy may be consuming artificial sweeteners in an effort to reduce calorie consumption."
"Because artificial sweeteners taste sweet but do not contain calories, it has been postulated that they ‘trick’ the brain into seeking out high-sugar, calorically dense foods in order to compensate for the lack of energy provided by the sweeteners...However, multiple studies support that consumption of artificial sweeteners either decrease or have no effect on subsequent energy intake or feelings of hunger."
"Because repeated exposure does train flavor preference, it certainly follows that consumption of artificial sweeteners could lead to increased sugar consumption. This may result in increased consumption of calorically dense foods and lead to excess energy intake. In short, the effect of artificial sweeteners on appetite and food preference is complicated. Though artificial sweetener consumption may decrease sensitivity to sweetness and increase sugar cravings for some, it appears that the exact opposite is true for others. At this point, it is unlikely that artificial sweetener intake directly increases appetite or energy intake in healthy humans and one’s behavioral response (i.e. higher or lower appetite, more or less cravings, etc.) seems to be dependent on the context and the individual."

In a later article (2021 June 4. Artificial sweeteners - a free lunch, or an obesogenic carcinogen? What 80+ studies say (part 2). Science-Based Medicine blog), Solokas dealt with proposed adverse effects:

"... there is no human evidence that shows AS consumption increases one’s risk of developing metabolic syndrome or diabetes."
"Most of the information regarding the effect of AS consumption on the gut microbiota is speculation derived from observational research and studies performed on rodents or petri dishes. There is a significant need for more well-designed studies in humans to assess this topic and, until that time, it is advised to proceed with caution. Consume AS in moderation or not at all if you have concerns about the health of your gut microbiota"
"You can rest assured that artificial sweetener intake has NOT been shown to cause cancer."

Beta glucans - "β-Glucans are natural bioactive fibers or polysaccharides composed of D-glucose monomers, linked by 1,3, 1,4, or 1,6 β-glycosidic bonds. They are naturally occuring in the cell wall of bacteria, fungi, algae, and higher crops, such as cereals and can be taken orally as a food supplement or as part of a daily diet" (Watanabe et al. 2020. Nutrients. 12:2873).

Presumed mechanism of action: inhibition of carbohydrate and lipid absorption

Review: Bessell et al. 2021. Int J Obes.45(8):1631-43: "One RCT reported a statistically and clinically significant weight change of -2.6 kg compared to placebo, while the other two RCTs reported a statistically but not clinically significant effect on weight compared to placebo (-1 kg and -1.8 kg, respectively)."

Notes: "While evidence supporting the use of β-Glucans 5–9 g/day as anti-diabetic and lipid-lowering dietary supplement are promising, data investigating their effects on body weight are lacking and uncertain, so no recommendation can be made regarding their use as weight loss supplements" (Watanabe et al. 2020. Op. cit.).

Bitter orange (Citrus aurantium) and p-synephrine

Presumed mechanism of action: Bitter orange "is rich in p-synephrine, a primary protoalkaloid which has been widely used for weight-loss management as suppressor of appetite and stimulator of energy expenditure and lipolysis" (Watanabe et al. 2020. Nutrients. 12:2873). "...the amount of p-synephrine can be artificially increased by concentrating the extract of natural products, and p-synephrine may be in a concentration of up to 19% in some commercially available dietary supplements. This allows the intake of moderate amounts of p-synephrine in one capsule or scoop of dietary supplements without the need of ingesting a large amount of fruit" (Ruiz-Moreno et al. 2021. Nutrients. 13(1):233).

Possible adverse effects: "Evidence for adverse reactions is not lacking, with C. aurantium being associated with diarrhoea, cardiovascular disease, hypertension, nausea/vomiting, migraines, insomnia, upper respiratory problems, skin damage, anxiety and cramping" (Farrington et al. 2019. J Integr Med. 17(2):87-92). “The NIH’s National Center for Complementary and Alternative Medicine says there ‘have been reports of fainting, heart attack and stroke in healthy people after taking bitter orange supplements alone or combined with caffeine.’ It adds, ‘there is currently little evidence that bitter orange is safer to use than ephedra’” (Healy. 2009 May 25. Here’s what’s really in those bottles. Los Angeles Times). On the other hand, Stohs (2017. Phytother Res. 31(10):1463-74) wrote, "This review, as well as several other assessments published in recent years, has concluded that bitter orange extract and p-synephrine are safe for use in dietary supplements and foods at the commonly used doses."

Review: Stohs et al. 2012. Int J Med Sci. 9(7):527-38: "p-Synephrine alone as well as in combination products were shown to increase resting metabolic rate and energy expenditure, and modest increases in weight loss were observed with bitter orange extract/p-synephrine-containing products when given for six to 12 weeks."

Notes: "Recent reviews of C. aurantium alone conclude that there is minimal objective evidence that consumption either reduces appetite or causes weight loss in humans" (Farrington et al. 2019. J Integr Med. 17(2):87-92). "At the moment, bitter orange should not be recommended for the treatment of obesity as the quality of evidence supporting its application for this purpose is low" (Watanabe et al. 2020. Nutrients. 12:2873). “With properties similar to ephedra, there are some serious health concerns that go along with Citrus aurantium. It is not recommended” (Mullin 2014. Nutr Clin Pract. 29(6):842-3). "...p-Synephrine became popular as an active ingredient for thermogenics and weight-loss supplements due to the ban of Ephedra species by the U.S. Food and Drug Administration in 2004. Several dietary supplements companies substituted Ephedra with Citrus aurantium or p-synephrine because they purportedly have the capacity to increase the metabolic rate at rest and enhance lipolysis" (Ruiz-Moreno et al. 2021. Op. cit.).

Caffeine

Presumed mechanism of action: "hunger suppression; energy expenditure stimulation; increased fat oxidation and brown adipose tissue activation" (Watanabe et al. 2020. Nutrients. 12:2873). "Despite some conflicting data, it is generally accepted that caffeine effectively stimulates the central nervous system and increases metabolic rate in humans. Caffeine functions through inhibition of phosphodiesterase (PDE) and through stimulation of adenosine receptors, leading to accumulation of intracellular 3,5-cyclic-adenosine monophosphate (cAMP) which is metabolically excitatory for cells" (Vaughan et al. 2014. ISRN Nutr. 2014:650264).

Possible adverse effects: “Caffeine is possibly unsafe when used for a long time or in doses over 400 mg daily. Caffeine can cause insomnia, nervousness, restlessness, nausea, increased heart rate, and other side effects. Larger doses might cause headache, anxiety, and chest pain. Caffeine is likely unsafe when used in very high doses. It can cause irregular heartbeat and even death. Products with very concentrated or pure caffeine have a high risk of being used in doses that are too high. Avoid using these products” (WebMD 2018. Caffeine - uses, side effects, and more).

Review: Tabrizi et al. 2019. Crit Rev Food Sci Nutr. 59(16):2688-96: "Overall, the current meta-analysis demonstrated that caffeine intake might promote weight, BMI and body fat reduction."

Notes: "Overall, moderate-quality evidence suggests that black and green coffee, and both caffeine and CGA [chlorogenic acid], may potentially induce weight loss, and they should be considered as a tool for the treatment of obesity. However, further studies are needed to better evaluate the effects of the single components on body weight" (Watanabe et al. 2020. Op. cit.). “In studies, high doses of caffeine have been shown to decrease appetite, but the effect doesn’t last long. The chemical also acts as a diuretic, prompting the release of retained water, which leads to short-term weight loss. ‘There is some evidence’ that caffeine can contribute to temporary weight loss, says Barbara Corkey, an obesity researcher...‘What caffeine can do is stimulate lipolysis, the breakdown of lipids, and that should, in theory, have a beneficial effect. But in practice it’s useless: The body is very smart about compensating for that...so it’s not a long-lasting, permanent effect’” (Healy 2009 May 25. Here’s what’s really in those bottles. Los Angeles Times).

Calcium

Presumed mechanism of action: “Joint supplementation of calcium and vitamin D is proposed to regulate adipocyte lipid metabolism and triglyceride storage, improving metabolic health and reducing body weight” (Batsis et al. 2021. Obesity. 29(7):1102-13).

Review: Batsis et al. 2021. Op. cit.: “Of the 22 studies, 8 did not report changes between arms over time; 3 studies (9%) demonstrated significant findings of decreased weight over time. Of the five articles with low bias (23%), none demonstrated significant differences in weight change between groups.”

Calorad - “Calorad Classic is a liquid dietary supplement composed primarily of 3,000 mg (3 grams) of Type II hydrolyzed collagen (hydrolysate) from either beef (bovine) or tuna (marine) sources and 8 mg of aloe vera, both of which are listed as active ingredients. The supplement label states that Calorad is fat-free and carbohydrate-free and that 1 serving (1/2 ounce) provides 3 grams of protein and 10 calories...The primary claim made for the product is that regular use causes weight loss without loss of lean muscle mass. While weight loss and body fat reduction may be achieved simply by following the labeled instruction to avoid eating within three hours prior to sleep as that can result in eating fewer calories per day, most individuals fasting for 3-hours prior to bed-time alone are not successful in accomplishing long-term weight loss” (Wikipedia 2022. Calorad).

Capsaicin - "Capsaicin is an active compound of chili peppers and a component of the capsaicinoids family...Capsinoids, also present in chili peppers, are structurally similar to capsaicinoids and bind to the same receptor, but they do not have the same characteristic pungency because they cannot reach mouth receptors due to their structural difference" (Watanabe et al. 2020. Nutrients. 12:2873).

Presumed mechanism of action: "Capsaicin effects are ascribable to the activation of transient receptor potential channel vanilloid type-1 (TRPV1), causing an influx of Ca2+, and subsequent release of neurotransmitters, such as substance P and catecholamines, and other substances like GLP-1. In animal models, capsaicin has also been shown to suppress ghrelin release, increase adiponectin mRNA expression in the adipose tissue and PPARα/PGC-1α mRNA in the liver, enhance AMPK and regulate gluconeogenesis and glycogen synthesis genes, thus reducing obesity-induced insulin resistance. Other studies have demonstrated that capsaicin and capsaicinoids are able to induce thermogenesis, activating UCP-1 and 2, increase fat oxidation, SNS activity, and energy expenditure via GI TRPV1 activation [170] and promote SIRT-1 expression, inducing browning of white adipose tissue" (Watanabe et al. 2020. Op. cit.).

Reviews:

Whiting et al. 2014. Appetite. 73:183-8: "Meta-analysis findings suggest that daily consumption of capsaicinoids may contribute to weight management through reductions in energy intake. Subsequently, there may be potential for capsaicinoids to be used as long-term, natural weight-loss aids."
Zsiborás et al. 2018. Crit Rev Food Sci Nutr. 58(9):1419-27: "Our data clearly suggest that capsaicin or capsiate could be a new therapeutic approach in obesity promoting a negative energy balance and increased fat oxidation."

Notes: "The body of evidence shows that Capsaicinoids and capsaicin are effective in promoting a negative energy balance short term via thermogenesis enhancement and energy intake reduction, especially in overweight and obese subjects. However, whether this translates in sustained weight loss is still unclear and the quality of evidence supporting its application for obesity treatment is low. Studies conducted in the past showed that the ability to influence energy balance is not always successful in obesity management. Furthermore, long term studies analyzing capsaicinoids effect on energy expenditure failed to demonstrate a beneficial effect consistently, and higher quality studies are therefore needed to elucidate their potential on weight management. Despite the quality of evidence being classified as low, the strength of preclinical evidence and the promising results from human studies, together with the good safety profile, may support the use of capsaicinoids and capsaicin for the treatment of obesity" (Watanabe et al. 2020. Op. cit.).

Caralluma - "Caralluma Fimbriata is an edible succulent plant belonging to the Asclepiadaceae family. It is found in Africa, India, Arabia, and Southern Europe" (Watanabe et al. 2020. Nutrients. 12:2873).

Presumed mechanism of action: "Pregnane glycosides, the main bioactive compounds, are thought to be the ones responsible for the reported appetite-suppressant and weight loss inducing properties of caralluma. This seems to be obtained through citrate lyase and malonyl coenzyme A inhibition that in turn leads to inhibition of fatty acid synthesis and enhanced fatty acid oxidation. Furthermore, caralluma glycosides also seem to reduce appetite by acting on the hypothalamus through the amplification of energy sensing function signalling or through the inhibition of ghrelin/neuropeptide Y expression" (Ibid..).

Notes: "Given the scarcity of data and the low-quality of the evidence on the anti-obesogenic effect of caralluma in human subjects, it is not possible at this time to recommend its use despite it being reasonably devoid of side effects" (Ibid.).

Carnitine - part of normal human metabolism but not required in diet.

Presumed mechanism of action: "increased energy expenditure and fat oxidation; improved insulin resistance; modulation of regulators of lipid catabolism or adipogenesis ; induction of satiety" (Watanabe et al. 2020. Nutrients. 12:2873).

Reviews:

Pooyandjoo et al. 2016. Obes Rev. 17(10):970-6: "Results from meta-analysis of eligible trials revealed that subjects who received carnitine lost significantly more weight...and showed a decrease in body mass index...compared with the control group. The results of meta-regression analysis of duration of consumption revealed that the magnitude of weight loss resulted by carnitine supplementation significantly decreased over time (p = 0.002). We conclude that receiving the carnitine resulted in weight loss."
Askarpour et al. 2020. Pharmacol Res. 151:104554: "Our study revealed that l-carnitine supplementation might have a positive effects in achieving an improved body weight and BMI especially in overweight and obese subjects."

Notes: "Evidence supporting the use of L-C as drug for weight loss in adults is still of low quality, but given the strength of preclinical evidence and the promising results from human studies, together with the good safety profile, this supplement could be considered as a treatment of obesity" (Watanabe et al. 2020. Op. cit.).

Cellasene - mixture of herbs and other ingredients claimed to reduce cellulite.

Notes: Claims seem dubious, and no published research in support. In July 2000 the FTC filed charges against the distributors for making unsupported claims. “The amount of fat in the body is determined by the individual’s eating and exercise habits, but the distribution of fat in the body is determined by heredity. In most cases reduction of a particular part can be accomplished only as part of an overall weight-reduction program” (Barrett 2000. “Cellulite” removers. Quackwatch).

Chitosan - chitin is a polymer of N-acetylglucosamine, found in some animal shells. Chitosan is deacetylated form. Polyglucosamine "is a low-molecular-weight chitosan acquired through marine sources and obtained after deacetylation of chitin with deacetylation degree (DD) of >70%" (Perna et al. 2020. Nutrients. 12(8):2365).

Presumed mechanism of action: binds fat and carries it through the digestive system. "Chitosan forms hydrophobic bonds with dietary cholesterol, therefore interfering with its emulsification and absorption" (Watanabe et al. 2020. Nutrients. 12:2873). "The potential anti-obesity effects of chitosan in vivo may include the modulation of adipokines, suggesting a second possible endocrine mechanism of action..." (Walsh et al. 2013. PLoS One. 8(1):e53828).

Possible adverse effects: people allergic to shellfish may suffer allergic reactions; however, chitosan derived from fungi is an alternative that would avoid this problem. Other possible adverse effects include heavy metal contamination, loss of fat-soluble vitamins, and intestinal bloating.

Reviews:

Moraru et al. 2018. Medicina (Kaunas). 54(6):109: "Based on the meta-analysis realized with 14 RCT we concluded that the usage of chitosan as a dietary supplement can lead to a slight short- and medium-term effect on weight loss and to the improvement of serum lipid profile and cardiovascular factors."
Perna et al. 2020. Op. cit.: "In conclusion, the use of polyglucosamine supplementation in conjunction with lifestyle behavioral therapies can be effective for weight reduction."
Bessell et al. 2021. Int J Obes.45(8):1631-43: "The meta-analysis found a statistically, but not clinically, significant difference in weight in those taking chitosan compared to placebo (p = 0.002) with considerable variability in the observed effect sizes."

Notes: "Given the low-quality evidence and the poor clinical importance of its consumption, but considering the mild if any adverse events, chitosan consumption cannot be encouraged nor discouraged as obesity treatment at this time" (Watanabe et al. 2020. Nutrients. 12:2873). The FTC took action against unsupported claims in 2005.

Chocolate and cocoa

Presumed mechanism of action: “Cocoa contains significant amounts of bioactive compounds, including antioxidant polyphenols and methylxanthines (caffeine and theobromine), which might promote weight loss by browning white adipocytes and improving lipid catabolic metabolism insulin resistance, endothelial function, and oxidative stress” (Batsis et al. 2021. Obesity. 29(7):1102-13).

Review: Batsis et al. 2021. Op. cit.: Of six trials carried out between 2008 and 2015, “One study demonstrated significant differences between arms at follow-up; the remaining were nonsignificant or did not report these values. The study with a low risk of bias did not show any significant changes in weight.”

Chromium - often sold as the picolinate salt

Presumed mechanism of action: "The exact mechanism of Cr is not well understood, however, salt forms, such as Cr nicotinate, Cr chloride, and Cr picolinate, are believed to be associated with an increase in the activity of insulin. Cr may also contribute to weight loss by suppressing appetite and by stimulating human thermogenesis, through sensitization of insulin-sensitive glucoreceptors in the brain, thus increasing energy expenditure" (Watanabe et al. 2020. Nutrients. 12:2873). “It may directly enhance serotonin activity and/or impact potential downstream effects on dopaminergic signaling on central insulin receptors. By altering these neurotransmitters, chromium is thought to affect several pathways involved in the central control of food intake, satiety, and energy hemostasis” (Batsis et al. 2021. Obesity. 29(7):1102-13).

Possible adverse effects: "Diarrhea, vertigo, headache, urticaria...studies have reported concerns regarding the safety of Cr picolinate supplementation which could be responsible for renal and hepatic impairment" (Watanabe et al. 2020. Op. cit.). Interactions with some medications.

Reviews:

Onakpoya et al. 2013. Obes Rev. 14(6):496-507: "The evidence from available RCTs shows that chromium supplementation generates statistically significant reductions in body weight. The magnitude of the effect is small, and the clinical relevance is uncertain."
Tian et al. 2013. Cochrane Database Syst Rev. CD010063: "We found no current, reliable evidence to inform firm decisions about the efficacy and safety of CrP [chromium picolinate] supplements in overweight or obese adults."
Tsang et al. 2019. Clin Obes. 9(4):e12313: "Chromium supplementation was associated with some improvements in body composition in subjects with obesity/overweight. The effect size was medium and the clinical relevance of chromium as a weight loss aid remains uncertain."
Batsis et al. 2021. Op. cit.: "Of the six trials [between 1996 and 2016], one did not report differences between groups, and of those that reported results, only two reported a significant weight loss. Of the three studies with low bias, only one demonstrated a significant reduction in weight (-1.4 ± 2.9 kg) with 400 µg of chromium over 72 days.”

Notes: "In conclusion, the evidence supporting the use of Cr for weight loss is moderate, although clinical relevance remains uncertain, possibly because of the presence of different forms of supplementation; further investigation through larger studies is necessary. However, given the less favorable safety profile compared to other food supplements, its use cannot be recommended nor discouraged at his time" (Watanabe et al. 2020. Op. cit.).

Cinnamon

Presumed mechanism of action: “Cinnamon is said to increase insulin sensitivity and decrease blood sugar - both key components for losing weight and controlling type 2 diabetes. Cinnamon is also thought to boost metabolism because your body uses more energy to process the spice than it does for other foods. It’s full of fiber, a nutrient that’s essential for achieving that ‘full’ feeling and signaling to your body that mealtime is over” (Lillien 2020. Does cinnamon help you lose weight? Verywell Fit).

Possible adverse effects: "Use in larger amounts or for long periods of time is sometimes associated with side effects, most commonly gastrointestinal problems or allergic reactions. Cassia cinnamon contains a chemical called coumarin, which can be harmful to the liver. Some cassia cinnamon products contain high levels of this substance...prolonged use of cassia cinnamon could be an issue for sensitive people, such as those with liver disease" (Zhu et al. 2020. Complement Ther Med. 53:102517).

Reviews:

Yazdanpanah et al. 2020. Phytother Res. 34(3):448-63: "Cinnamon supplementation significantly reduces body weight, BMI, and WHR. Future high-quality long-term RCTs are recommended to confirm these results."
Mousavi et al. 2020. Clin Nutr. 39(1):123-33: "Cinnamon supplementation significantly affects obesity measures. It could be recommended as a weight-reducing supplement in obesity management."

Notes: “When it comes to being a metabolism booster, hard data is minimal. And while it is well documented that fiber helps you feel full and that a high-fiber diet can be helpful for weight loss, it's unlikely you'll get much fiber from cinnamon alone. One can only consume so much cinnamon in a day” (Lillien 2020. Op. cit.).

Citrus aurantium - see bitter orange

Cocoa - see chocolate

Coleus forskohlii

Presumed mechanism of action: "Forskolin is a labdane diterpene isolated from the roots of C. forskohlii, which acts directly on adenylate cyclase to produce the second messenger, cAMP, which then stimulates the breakdown of fat in human and animal fat cells. This stimulation of fat breakdown could lead to weight loss" (Farrington et al. 2019. J Integr Med. 17(2):87-92).

Notes: "Despite promotion as a weight loss supplement, there is little evidence to support this" (Ibid.).

Conjugated linoleic acid - a group of isomers of linoleic acid. "CLA is formed naturally via the biohydrogenation of fats by bacteria in the gastrointestinal tract of ruminants. This involves changing the position and configuration of the double bonds of poly-unsaturated fats, producing, for example, trans-10, cis-12 (t10-c12) or cis-9, trans-11 (c9-t11), which are the CLA isomers of greatest biological activity" (Bessell et al. 2021. Int J Obes.45(8):1631-43).

Presumed mechanism of action: "Several possible mechanisms have been suggested possibly aiding weight loss in animal models and human subjects. First, supplementation with CLA was shown to decrease the size of adipocytes, alter adipocyte differentiation, stimulate apoptotic pathways, and regulate lipid metabolism. Moreover, some works suggested greater activation of PPAR-γ receptors and pro-inflammatory cytokines, fatty acids oxidation, and the browning of white adipose tissue as a mechanism of fat mobilization. Finally, adding CLA to the diet could also alter the gut microbiota composition and associated gut metabolites" (Watanabe et al. 2020. Nutrients. 12:2873).

Possible adverse effects: gastrointestinal discomfort. "Researchers have found that it can increase blood levels of C-reactive protein, lipoprotein, and leptin - all of which can heighten the risk of heart disease. There is also some evidence that taking CLA daily increases insulin resistance, a sign of impending Type 2 diabetes" (O'Connor 2007 May 29. The claim: C.L.A. supplements can help you lose weight. New York Times).

Reviews:

Namazi et al. 2019. Crit Rev Food Sci Nutr. 59(17):2720-33: "Supplementation with CLA can slightly reduce body weight and FM and increase LBM in overweight and obese subjects. However, its efficacy was not clinically considerable."
Bessell et al. 2021. Op. cit.: After excluding two studies for incomplete data, "In the eight remaining RCTs (568 participants) which were included in our meta-analysis, the weight difference in groups using CLA compared to placebo was statistically but not clinically significant."
Batsis et al. 2021. Obesity. 29(7):1102-13: Of 31 trials published between 2001 and 2016, only five had low degree of bias. Of these, "only one demonstrated a statistically significant weight loss."

Notes: "In conclusion, the literature to date suggests that CLA, and primarily the 10,12 CLA isomer, promotes weight and fat loss in human subjects. Although its effectiveness seems to be clinically limited and the quality of evidence low, CLA could be considered as a treatment of obesity in addition to a dietary program given the strong preclinical evidence, the minor weight loss effect, and the very good safety profile" (Watanabe et al. 2020. Op. cit.).

CortiSlim and similar products to control cortisol

Presumed mechanism of action: control cortisol levels; it also contains ingredients that are alleged to be thermogenic and to control blood glucose. They “are widely marketed as weight-loss aids on the argument that stress - which causes the release of the hormone cortisol - can lead to weight gain and, particularly, to the accumulation of belly fat” (Healy 2009 May 25. Here’s what’s really in those bottles. Los Angeles Times).

Notes: “In 2007, the Federal Trade Commission charged the marketers of two products - CortiSlim and CortiStress, with making false and unsubstantiated claims about their product's weight-loss properties, leading to a multimillion dollar settlement...There is no evidence that blocking cortisol causes weight loss, or that herbal remedies lower cortisol levels, according to the Mayo Clinic’s Katherine Zeratsky, a dietitian. In fact, the accumulation of fat due to high levels of cortisol appears to happen only in cases where there is an underlying medical issue, such as Cushing’s disease, or as a side effect of certain drugs” (Healy 2009. Op. cit.).

Curcumin - "Curcumin is a bioactive polyphenol component derived from turmeric, a rhizomatous herbaceous perennial plant (Curcuma longa)" (Watanabe et al. 2020. Nutrients. 12:2873).

Presumed mechanism of action: "adipogenesis inhibition; insulin-sensitizing and anti-inflammatory properties" (Ibid.).

Possible adverse effects: "Curcumin supplementation is considered safe and no adverse side effects have been reported at low doses, while mild side effects such as digestive issues, headaches, nausea, or skin rashes have been rarely reported at higher doses (0.5–12g)" (Ibid.).

Notes: "Overall, evidence supporting the use of curcumin for weight loss are low in quality. Therefore, treatment with curcumin for weight loss purposes should be proposed only when a favorable cost-to-benefit ratio has been found and side effects should be looked for, especially when higher dosages are being proposed" (Ibid.).

Diacylglycerol - "Diacylglycerol (DAG) is a natural component of several edible oils such as rapeseed and cottonseed oil, and is therefore easily added to foods" (Watanabe et al. 2020. Nutrients. 12:2873).

Presumed mechanism of action: "DAG enhances fat oxidation and decreases the re-synthesis of chylomicrons in animal models, and its peculiar structural and metabolic characteristics seem to be responsible for the suppression of body fat accumulation, body weight loss and lower postprandial serum TG levels found upon the consumption of DAG-rich oils" (Ibid.).

Possible adverse effects: Generally recognized as safe by FDA.

Review: Xu et al. 2008. Asia Pac J Clin Nutr. 17(3):415-21: "In conclusion, this meta-analysis suggested that DAG was efficacious for reducing body weight compared with TAG and this effect was influenced by the daily dose."

Notes: "Overall, moderate-quality evidence suggests that DAG at a dosage of 1.1–1.2 g/day is effective in reducing body weight in both healthy and diabetic subjects compared to TAG, leading to a reduction in cardiovascular risk, with no adverse events being reported, and its use as a weight loss supplement could therefore be recommended" (Watanabe et al. 2020. Op. cit.).

2,4-Dinitrophenol - an uncoupler of oxidative phosphorylation. Thus, it can increase cellular respiration and consumption of calories without exercise. However, it is extremely toxic, leading to serious side effects (including death).

Enviga - a carbonated beverage containing green tea extract, caffeine, and other ingredients. The green tea extract is said to be high in epigallocatechin gallate (EGCG) (see discussion of green tea below). Scientists from the Center for Science in the Public Interest "have concluded that 'Enviga is just a highly caffeinated and overpriced diet soda, and is exactly the kind of faddy, phony diet aid it claims not to be'" (Barrett 2007. Claims for Enviga challenged. Quackwatch). In 2009 the manufacturers reached a settlement concerning unsubstantiated weight loss claims; a lawsuit had been brought by 26 states plus the District of Columbia.

Epigallocatechin gallate (EGCG) - see green tea

Fenugreek

Notes: "No studies to date have shown that fenugreek induces weight loss. This is a supplement that I may recommend for blood sugar control issues, but leave it off the list of supplements that help with weight loss (Mullin 2015. Nutr Clin Pract. 30(3):446-9).

Fish oil, omega 3 fatty acids

Presumed mechanism of action: "Animal studies have consistently shown that fish oil may increase resting energy expenditure; increase fat burning; suppress appetite; turn on genes involved in fat oxidation in the liver, heart, intestine, and skeletal muscles; turn off genes that cause new fat cells to be created in adipose tissue; and lead to more lean muscle mass. Unfortunately, little research has been done to corroborate these effects in humans, and the studies to date are relatively small" (Mullin 2015. Nutr Clin Pract. 30(3):446-9).

Notes: "Some evidence—not enough for a strong recommendation for weight loss specifically" (Ibid.).

Flaxseed - "Flaxseed is a functional food sourced from the flax plant; it is rich in a-linolenic acid (ALA), dietary fiber and lignans (phytoestrogen)" (Watanabe et al. 2020. Nutrients. 12:2873).

Presumed mechanism of action: "Many flaxseed components may have positive effects on weight management: lignans are reported to reduce visceral fat and increase fat oxidation and adiponectin levels in mice...; soluble fiber...may induce a feeling of fullness, delay gastric emptying and increase SCFA concentration in the gut, inducing satiety and promoting weight loss via GI hormones release. Furthermore, ALA has been shown to increase adipose leptin expression in animal models and flaxseed polysaccharides have been able to induce satiety improving leptin resistance together with enhancing lipolysis and suppressing lipogenesis through the AMPK signaling pathway. Lastly, ALA metabolism products, eicosapentaenoic acid and docosahexaenoic acid, were able to induce adipocytes apoptosis, suppress appetite and enhance fat oxidation and energy expenditure in animal models" (Ibid.).

Review: Mohammadi-Sartang et al. 2017. Obes Rev. 18(9):1096-107: "Whole flaxseed is a good choice for weight management particularly for weight reduction in overweight and obese participants."

Notes: The above review (Mohammadi-Sartang et al. 2017. Op. cit.) found that "only whole flaxseed was able to reduce body weight, BMI, and waist circumference, while flaxseed oil and lignans extracts did not show any benefit. Furthermore, a significant weight loss was observed only in subjects with BMI >27, eating more than 30 gr of flaxseed per day and in trials longer than 12 weeks. These findings suggest that the high fiber content or other compounds present in whole flaxseed are responsible for the higher weight loss. These results may also indicate that flaxseed supplementation has a cumulative and time dependent effect, probably because ALA, lignans or other flaxseed components build up their concentration in tissues over time or because of gut microbiota adaptations happening over a longer period...Overall, flaxseed showed promising weight reduction properties, backed by numerous health benefits, although the quality of the evidence supporting its application for this purpose is still low; however, considering the absence of side effects, its consumption may be considered for the treatment of obesity" (Watanabe et al. 2020. Op. cit.).

Fructans - short and long-chain polymers of fructose

Possible adverse effects: High doses have produced severe gastrointestinal side effects.

Review: Bessell et al. 2021. Int J Obes.45(8):1631-43: "The meta-analysis of the 261 participants available at the end of intervention in these four RCTs reported no statistically significant difference between fructans and placebo (p = 0.24), with considerable heterogeneity between RCTs."

Garcinia cambogia - (Garcinia gummi-gutta, Malabar tamarind) "is native to Southeastern Asia. The fruit rind is commonly used as a food preservative, flavouring agent or food-bulking agent, and as a traditional remedy...in many Asian countries" (Semwal et al. 2015. Fitoterapia. 102:134-48). The major component is hydroxycitric acid (HCA) (hydroxycitrate).

Presumed mechanism of action: HCA is an inhibitor of an enzyme (ATP citrate lyase) needed for formation of malonyl CoA. Since malonyl CoA inhibits fatty acid oxidation, hydroxycitrate could therefore increase fatty acid oxidation. Reduction of appetite (by increasing serotonin) is also proposed. "Pre-clinical studies also demonstrated that GC extracts attenuated fat accumulation through regulation of lipolysis genes expression via the adiponectin-AMPK signaling pathway" (Watanabe et al. 2020. Nutrients. 12:2873).

Possible adverse effects: Hepatotoxicity and diarrhea. "Although in short term trials GC has been proven as generally safe, it is noteworthy to underline that FDA urged consumers to avoid Hydroxycut, a natural product for weight loss containing GC and a variety of other ingredients, because of the report of twenty-three cases of hepatotoxicity associated with its use in 2009. Moreover, several hepatoxicity cases have been associated also with the use of pure GC extracts (Watanabe et al. 2020. Op. cit.).

Reviews:

Onakpoya et al. 2011. J Obes. 2011:509038: " It is concluded that the RCTs suggest that Garcinia extracts/HCA can cause short-term weight loss. The magnitude of the effect is small, and the clinical relevance is uncertain. Future trials should be more rigorous and better reported."
Golzarand et al. 2020. Complement Ther Med. 52:102451: "Our results suggested that Garcinia cambogia supplement had a significant effect on the body weight, BMI, PFA [sic; should be PFM], and WC as compared with the placebo."

Notes:

"Thus, there is evidence that G. cambogia may act as a weight loss agent in the short term. As human trials have been short, with small sample sizes, it is unclear how effective G. cambogia would be for weight control over a longer period" (Farrington et al. 2019. J Integr Med. 17(2):87-92).
"Overall, the use of GC supplements as treatment for weight excess is to discourage considering the uncertainty of its clinical efficacy and the safety concerns" (Watanabe et al. 2020. Op. cit.).
Hydroxycut, a popular weight loss supplement, originally contained hydroxycitrate, ephedra, and other ingredients; after FDA actions due to toxicity (see above) it was reformulated and no longer contains hydroxycitrate and ephedra.
The prospects for HCA "were considered sufficiently promising that pharmaceutical giant Hoffman-LaRoche in the 1960s committed significant funds to develop it as a possible weight-loss pill. The company dropped it, however, when rat studies showed that, at doses that appeared effective at reducing fat deposits, hydroxycitrate caused 'potent testicular atrophy and toxicity'" (Healy 2009 May 25. Here’s what’s really in those bottles. Los Angeles Times).

Ginger

Presumed mechanism of action: "Many studies show that ginger may influence body weight reduction by increasing thermogenesis, release of catecholamines...and lipolysis in white adipose tissue...The mechanism by which ginger can control appetite seems to be through serotonin modulation and binding to 5-HT2c receptors, which regulate satiety..." (Tramontin et al. 2020. Phytother Res. 34(6):1282-90).

Possible adverse effects: heartburn, abdominal discomfort. May interact with blood thinners.

Review: Maharlouei et al. 2019. Crit Rev Food Sci Nutr. 2019;59(11):1753-66: “The results indicated that the supplementation with ginger significantly decreased body weight...”

Ginseng - see detailed discussion in HERBS article.

Presumed mechanism of action: "Ginseng is supposed to contribute to weight loss through its elevated content of saponins which can delay the intestinal absorption of dietary fat by inhibiting pancreatic lipase activity. Moreover, ginseng intake may affect serum levels of leptin, adiponectin, and ghrelin" (Watanabe et al. 2020. Nutrients. 12:2873).

Possible adverse effects: nervousness, excitation, headache, insomnia, palpitations, hypoglycemia, nausea, diarrhea, itching; estrogenic effects, vaginal bleeding. Reduces effects of warfarin and some other drugs.

Notes: "In conclusion, the clinical relevance of ginseng as a weight loss aid remains uncertain, as the evidence quality supporting its use is low and the dose range very high (100 mg–18 g/day)" (Ibid.).

Glucomannan - "a polysaccharide composed of β-1,4–linked D-mannose and D-glucose monomers which comes from the tuber Amorphophallus konjac. It is a soluble fiber which is present naturally and abundantly in several products, such as softwoods, roots, tubers, and many plant bulbs" (Watanabe et al. 2020. Nutrients. 12:2873).

Presumed mechanism of action: "It has been suggested that the ingestion of glucomannan could determine the prolongation of gastric emptying time, thus resulting in increased satiety and decreased post-prandial glucose concentration. Moreover, glucomannan is able to absorb up to 50 times its weight in water and cannot be digested by human salivary and pancreatic amylase so that it passes relatively unchanged into the colon, where it is fermented by the gut microbiota" (Ibid.).

Possible adverse effects: gastrointestinal disturbances

Reviews:

Sood et al. 2008. Am J Clin Nutr. 88(4):1167-75: "Glucomannan appears to beneficially affect total cholesterol, LDL cholesterol, triglycerides, body weight, and FBG, but not HDL cholesterol or BP."
Onakpoya et al. 2014. J Am Coll Nutr. 33(1):70-8: "The evidence from available RCTs does not show that glucomannan intake generates statistically significant weight loss."
Bessell et al. 2021. Int J Obes.45(8):1631-43: "In the meta-analysis of these seven RCTs using glucomannan, with end-point data from 539 participants, a statistically, but not clinically, significant difference in weight compared to placebo was found."

Notes: "The clinical relevance of glucomannan as a weight loss aid remains uncertain and the quality low. Further investigation through larger studies is necessary. At the moment, the consumption of glucomannan for the treatment of obesity should not be encouraged nor recommended against" (Watanabe et al. 2020. Op. cit.). "Glucomannan may facilitate weight loss, but the evidence is weak—more studies are needed" (Mullin 2015. Nutr Clin Pract. 30(3):446-9).

Grapefruit

Presumed mechanism of action: "Among its polyphenols, naringin and hesperidin have demonstrated antioxidant, lipid lowering and antihypertensive properties in animal models as well as human clinical trials. Naringin and hesperidin are also able to improve glycemic control, enhancing insulin secretion and inhibiting gluconeogenesis; like many other polyphenols, naringin has also been reported to stimulate the AMPK pathway, thus enhancing fatty acid oxidation and inhibiting lipogenesis. Cells and animal studies demonstrated lipolytic effects of grapefruit extract and polyphenols through the inhibition of cAMP-phosphodiesterase and activation of hepatic peroxisome proliferator-activated receptor γ and α" (Watanabe et al. 2020. Nutrients. 12:2873).

Possible adverse effects: interactions with some drugs

Review: Onakpoya et al. 2017.Crit Rev Food Sci Nutr. 57(3):602-12: "A meta-analysis for change in body weight failed to reveal a significant difference between grapefruits and controls...Paucity in the number of RCTs, short durations of interventions, and lack of an established minimum effective dose limit the conclusions that can be drawn about the effects of grapefruit on body weight and metabolic parameters."

Notes: "Overall, low-quality evidence supports grapefruit or grapefruit juice as a weight loss agent. Moreover, grapefruit may alter the metabolism of several drugs through cytochrome P450 interactions. This aspect should be therefore be kept in mind in those on a daily pharmacological treatment, and the consumption of high amounts of grapefruit should be therefore discouraged in these subjects. Altogether, its use cannot be recommended at this time" (Watanabe et al. 2020. Op. cit.).

Green coffee extract - coffee beans are extracted before roasting, which preserves some chemicals that are destroyed by heating.

Presumed mechanism of action: effects could be due to chlorogenic acid and/or caffeine. Studies in mice "showed that the mechanism of action involved downregulation of genes that turn on fat cell formation and inflammation. And in a corroborating study, scientists demonstrated that decaffeinated GCBE liberates free fatty acids from fat cells, while yet another study showed that it decreases pancreatic fat-digesting enzyme activity, leaving intestinal fat potentially less digestible" (Mullin 2015. Nutr Clin Pract. 30(2):311-2). Another proposed mechanism is inhibition of glucose absorption.

Reviews:

Gorji et al. 2019. Phytomedicine. 63:153018: "The results of current meta-analysis study support the use of GCE supplementation for the improvement of obesity indices, with sub-group analysis highlighting greater improvements in individuals with a starting BMI ≥25 kg/m2."
Asbaghi et al. 2020. Complement Ther Med. 51:102424: "We found that GCE supplementation had a beneficial effect on body weight, BMI and WC. It provides a cost-effective and safe alternative for the treatment of obesity. Additional well-designed studies are required to further confirm our findings."

Notes: Sales exploded in 2012 after publicity on the Dr. Oz show and other television programs. However, the small study cited in support was fraudulent and was later retracted. The FTC took action against major marketers in 2014 and 2015 for their deceptive claims.

Green tea - see detailed discussion under "tea" in HERBS article.

Presumed mechanism of action: "lipase, amylase, glucosidase inhibition; gut microbiota modification" (Watanabe et al. 2020. Nutrients. 12:2873) ;thermogenic effects. An important ingredient is epigallocatechin gallate (EGCG).

"The mechanism of action of green tea can be outlined as influencing the sympathetic nervous system, thereby increasing energy consumption and triggering the oxidation of fat. Reduced nutrient absorption, appetite prevention, and up-regulation of enzymes responsible for hepatic fat oxidation may also be enumerated as alternative mechanisms" (Esteghamati et al. 2015. Int J Endocrinol Metab. 13(2):e19678).
"Other teas such as black tea, thearubigins, and theaflavins share similar effects to those found in green tea. Green tea extract appears to offer some thermogenic effect when coupled with caffeine resulting in increased energy expenditure. In contrast, isolated green tea polyphenol ingestion independent of caffeine does not appear to increase metabolic rate; however it does increase indicators of fat metabolism in some populations. Green tea is purported to function by inhibiting the degradation of β2-adrenergic receptor agonists such as norepinephrine by the enzyme catechol O-methyltransferase (COMT), thereby increasing intracellular cAMP...In addition to COMT inhibition, it is theorized that effects of green tea extract are also a function of metabolic gene activation. Specifically, green tea may function to inhibit adipogenic genes such as peroxisome proliferator- activated receptor (PPARγ) and sterol regulatory element binding protein-1c (SREBP-1c) and increase the expression of genes that increase energy expenditure and mitochondrial biogenesis including nuclear respiratory factors (NRF), mitochondrial uncoupling protein-3 (UCP3), peroxisome proliferator-activated receptor (PPARα), and peroxisome proliferator-activated receptor γ coactivator-1a (PGC-1α), leading to increased oxidative and metabolic capacities" (Vaughan et al. 2014. ISRN Nutr. 2014:650264).
"Catechins may attenuate lipid emulsification...However, catechins may also inhibit the activity of gastric and pancreatic lipases. Therefore, impeding both lipid emulsification and lipid digestion may cause a decrease in dietary fat absorption" (Janssens et al. 2015. J Nutr. 145(5):864-70).

Possible adverse effects: EGCG, as an extract, can cause liver damage. "Case reports of green tea extract hepatotoxicity are linked to higher concentrations of EGCG, which exerts its toxic effects through generation of reactive oxygen species, mitochondrial damage, and depletion of glutathione in hepatocytes. In animal models, consumption of EGCG while fasting leads to greater morbidity due to higher plasma concentrations, a troubling fact since many weight loss supplements are taken with a low-calorie diet" (Whitsett et al. 2014. ACG Case Rep J. 1(4):220-2).

Reviews:

Jurgens et al. 2012. Cochrane Database Syst Rev. CD008650: "Green tea preparations appear to induce a small, statistically non-significant weight loss in overweight or obese adults. Because the amount of weight loss is small, it is not likely to be clinically important. Green tea had no significant effect on the maintenance of weight loss."
Pilou et al. 2016. Physiol Behav. 162:83-7: "a mixture of green tea catechins and caffeine has a beneficial effect on body-weight management, especially by sustained energy expenditure, fat oxidation, and preservation of fat free body-mass, after energy restriction induced body-weight loss, when taking the limitations into account."
Vázquez Cisneros et al. 2017. Nutr Hosp. 34(3):731-7: "Research has been very varied, however, daily consumption of green tea with doses of EGCG between 100 and 460 mg/day has shown greater effectiveness on body fat and body weight reduction in intervention periods of 12 weeks or more."
van Baak and Mariman 2019. Nutrients. 11(8):1916: "Studies investigate increased protein intake..., lower dietary glycemic index..., green tea (three studies), conjugated linoleic acid..., higher fibre intake..., and other miscellaneous interventions... The meta-analysis shows a significant beneficial effect of higher protein intake on the prevention of weight regain...No significant effect of the other strategies is detected."
Batsis et al. 2021. Obesity. 29(7):1102-13: of 16 trials published between 2005 and 2017 and having low risk of bias, only two showed statistically significant improvements in weight.

Notes: According to NCCIH (2016. Green tea), "Green tea extracts haven’t been shown to produce a meaningful weight loss in overweight or obese adults. They also haven’t been shown to help people maintain a weight loss." Watanabe et al. 2020. Op. cit.) wrote, "The effectiveness of GT in reducing body weight and fat is widely discussed in the literature. GT derived EGCG in variable quantities (100–460 mg/day) exhibits measurable weight-loss properties in a large majority of studies according to a recent review and one meta-analysis, especially for trial durations of three or more months...In conclusion, GT, alone or in association with other weight loss interventions, seems a possibly useful tool for the treatment of obesity with close to no side effects, and evidence supporting its consumption is of moderate quality. The exact reason behind the presence of controversial results is yet to be elucidated: it has been hypothesized that one possible motivation might be the use of relatively low doses of EGCG (i.e., 200 mg/daily), but some studies investigating the effect of low amounts still reported positive outcomes." Mullin (2015. Nutr Clin Pract. 30(3):446-9) wrote: EGCG "works not only to help you lose weight but to keep it off. But it works in tea, not as a supplement." EGCG supplements are not recommended due to its potential for liver damage.

Guar gum - "Guar gum, also known as 'guaran,' is a fiber derived from the seed of Cyamopsis tetragonolobus, an Indian leguminous plant. From a molecular point of view, guar gum is a complex polysaccharide called galactomannan, which is a polymer of D-galactose and D-mannose. It is widely used as an additive in food, in the form of guar gum powder. Guar gum can be also found in several types of food such as dairy products, cereals, sauces, pudding, kefir, and baked goods" (Watanabe et al. 2020. Nutrients. 12:2873).

Presumed mechanism of action: "It has been suggested that guar gum may contribute to lower body weight by increasing the viscosity of the bowel content and the feeling of postprandial fullness, thus reducing appetite and food intake" (Ibid.).

Possible adverse effects: gastrointestinal discomfort

Review: Pittler and Ernst 2001. Am J Med. 110(9):724-30: "This meta-analysis suggests that guar gum is not efficacious for reducing body weight. Considering the adverse events associated with its use, the risks of taking guar gum outweigh its benefits for this indication. Therefore, guar gum cannot be recommended as a treatment for lowering body weight."

Notes: "These results suggest that, although guar gum can lower cholesterol levels and improve insulin sensitivity compared with placebo, it seems not to be effective in lowering body weight and it should therefore be administered together with appropriate dietary manipulation" (Watanabe et al. 2020. Op. cit.). "Not recommended. While the theoretical basis for this supplement is sound, the data do not show that it provides the hoped-for benefits. Stick with psyllium as a fiber supplement" (Mullin 2015. Nutr Clin Pract. 30(3):446-9).

Guarana

Presumed mechanism of action: "Its fruit and seed are rich in catechins and methylxantines, that inhibit adipogenesis, promote browning in animal models, and stimulate energy expenditure in humans...its combination with other supplements is reported to delay gastric emptying leading to increased satiety and significant weight loss" (Watanabe et al. 2020. Nutrients. 12:2873).

Possible adverse effects: "A number of adverse events have been reported with guarana, including irritability, heart palpitations, anxiety, and other central nervous system events" (Medscape 2008. The skinny on weight loss supplements: fact or fantasy?).

Notes: "Despite the promising preclinical evidence, the paucity of data and the low-quality evidence regarding the effects of guarana consumption on weight loss in human subjects makes its potential application as therapeutic agent to treat obesity uncertain, so its consumption should be not encouraged to induce weight loss" (Watanabe et al. 2020. Op. cit.).

HCG (human chorionic gonadotropin) - a hormone produced during pregnancy

Presumed mechanism of action: "Products marketed for weight loss that claim to contain HCG are typically marketed in connection with a very low-calorie diet, usually one that limits calories to 500 per day. Many of these popular HCG products claim to 'reset your metabolism,' change 'abnormal eating patterns,' and shave 20 to 30 pounds in 30 to 40 days" (FDA 2020. Avoid dangerous HCG diet products).

Possible adverse effects: "Living on 500 calories a day is not only unhealthy but also dangerous. People on such restrictive diets are at increased risk for side effects, including gallstone formation, an imbalance of the electrolytes that keep the body’s muscles and nerves functioning properly, and an irregular heartbeat. Such restrictive diets can be dangerous, even potentially fatal...Without medical oversight, people on very low-calorie diets may not be getting enough vitamins, minerals and - most important - protein" (Ibid.).

Notes: "'These products are marketed with incredible claims, and people think that if they're losing weight, HCG must be working,' said Carolyn Becker, director of the Office of Unapproved Drugs and Labeling Compliance in the FDA’s Center for Drug Evaluation and Research. 'But the data simply do not support this; any loss is from severe calorie restriction. Not from the HCG.' The FDA has approved HCG as a prescription drug for the treatment of female infertility and for other medical conditions. HCG is not approved for use without a prescription for any purpose. It is not approved for weight loss" (Ibid.). Harvard's Dr. Pieter Cohen, an expert on dietary supplements, said "the use of hCG as a diet tool was 'manipulating people to give them the sense that they're receiving something that's powerful and potent and effective, and in fact they're receiving something that's nothing better than a placebo.' But unlike other popular diet supplements, hCG...has acquired an aura of respectability because the injections are available only by prescription" (Hartocollis 2011 Mar. 7. Diet plan with hormone has fans and skeptics. New York Times). In addition, products claiming to be homeopathic HCG (and therefore containing no actual active ingredients) have been marketed as over-the-counter supplements. The FDA took action against these in 2011.

Hoodia gordonii - southern African plant, said to suppress appetite.

Presumed mechanism of action: "The active compound, steroidal glycoside p57, is associated with altering neuropeptide-mediated pathways of the central nervous system and inhibiting appetite by affecting hypothalamic neurons and the hypothalamus" (Farrington et al. 2019. J Integr Med. 17(2):87-92).

Possible adverse effects: "Little is known about the safety of hoodia. However, the one completed study in people raises concerns. In that study, participants taking hoodia had more side effects than those taking placebos, including nausea, vomiting, dizziness, and odd skin sensations. Of concern, hoodia significantly affected some clinical and safety parameters, such as blood pressure, bilirubin, and electrocardiogram (heart function) measures. Little is known about whether it’s safe to use hoodia during pregnancy or while breastfeeding" (NCCIH 2020. Hoodia).

Notes: "Despite its popularity as a weight loss product, there are limited scientifically based studies on clinical relevance, bioactivity or the in vivo biopharmaceutical behaviour of H. gordonii" (Farrington et al. Op. cit.). "We know very little about hoodia because only one study of this herb has been done in people...The one small study of hoodia in people involved women who were overweight. Those who took hoodia for 15 days didn't lose more weight than those who took a placebo" (NCCIH 2020. Hoodia). In 2009 the FTC charged marketers of Hoodia products with deceptive advertising.

Hydroxycitrate - see Garcinia cambogia.

Inulin - "Inulin is a polysaccharide produced by many plants and extracted principally from chicory. It is part of the inulin-type fructans (ITFs) family which covers all β (2←1) linear fructose polymers, such as native inulin, oligofructose and fructo-olysaccharides (FOS). These compounds are resistant to digestion and undergo a selective fermentation, thus acting as dietary fiber and bifidogenic prebiotic. Inulin is also used as a fat and sugar replacement and texture modifier in many bakery, dairy and meat products" (Watanabe et al. 2020. Nutrients. 12:2873).

Presumed mechanism of action: "ITFs have been shown to be capable of regulating GI hormones release in both animals and humans: inulin and FOS supplementation are able to increase Gucagon like petide -1 [sic] (GLP-1) and PYY release and suppress ghrelin secretion; furthermore, the prebiotic properties of ITFs may modulate the gut microbiota, favoring the growth of beneficial bacteria such as short-chain fatty-acids (SCFA) producers, thus improving satiety and weight loss and reducing systemic inflammation. Whether these proposed mechanisms of action are able in turn to suppress appetite and promote weight loss is a matter of debate..." (Watanabe et al. 2020. Op. cit.).

Possible adverse effects: “Inulin is likely safe for most people in the amounts found in foods. It is possibly safe in adults when taken as a supplement, short-term. Doses of 8-18 grams daily have been used safely for up to 24 weeks. The most common side effects include gas, bloating, diarrhea, constipation, and cramps. These side effects are more severe with high doses of inulin (more than 30 grams)” (WebMD 2020. Inulin - uses, side effects, and more).

Review: Liber et al. 2013. Ann Nutr Metab. 63(1-2):42-54: "Limited data suggest that long-term administration of ITF may contribute to weight reduction."

Notes: "Overall, most evidence shows that inulin and ITFs supplementation has a positive effect in subjects with T2D regarding weight loss, appetite suppression, glucose metabolism and systemic inflammation parameters, while such effects have not been described consistently in those with obesity but no diagnosis of T2D. Noteworthy, the quality of evidence supporting the application of inulin for weight loss is low...At this time, inulin should be not recommended for the treatment of obesity, although it may be considered in obese patients suffering from T2D" (Watanabe et al. 2020. Op. cit.).

Konjac root - see glucomannan

Licorice - from the root of Glycyrrhiza glabra.

Presumed mechanism of action: "reduced serum lipids; improved hepatic steatosis through beta-oxidation induction" (Watanabe et al. 2020. Nutrients. 12:2873).

Possible adverse effects: numerous potentially serious side effects due to mineralocorticoid action. High blood pressure, low potassium levels.

Reviews:

Luís et al. 2018. Phytomedicine. 39:17-24: "The present meta-analysis demonstrated the positive effects of licorice consumption on the reduction of body weight and BMI of patients. However, the results also show the increase in blood pressure of patients associated with the hypernatremia caused by licorice. Consequently, licorice consumption should be avoided by hypertensive patients."
Bessell et al. 2021. Int J Obes.45(8):1631-43 (reviewing two trials of Kaneka Glavonoid, a licorice flavonoid oil product): "One of the RCTs reported a statistically significant weight difference of -0.7 kg in the treatment compared to placebo, while the other RCT reported a statistically significant weight difference of -1.0 kg with the highest dose of LFO compared to placebo. These weight losses were below our threshold of clinical significance."

Notes: "Overall, evidence supporting the use of licorice or licorice extract for weight loss is conflicting and of low-quality. Given the negative effects of licorice on blood pressure, and being hypertension a common complication in patients with weight excess, the use of this dietary supplement should be discouraged at this time" (Watanabe et al. 2020. Op. cit.).

Lipoic acid (alpha lipoic acid) - part of normal human metabolism, not required in the diet

Presumed mechanism of action: "improved glucose metabolism; appetite suppression; increase of lipolysis and reduction of lipogenesis...LA seems to lead to increased GLUT4 expression on the cell membrane of skeletal muscle and adipocyte cells, through a PI3K-dependent mechanism that involves the insulin signaling cascade" (Watanabe et al. 2020. Nutrients. 12:2873).

Possible adverse effects: "Gastrointestinal disconfort [sic], urticaria, hypoglycemia" (Ibid.). Cases of insulin autoimmune syndrome have been reported.

Review: Kucukgoncu et al. 2017. Obes Rev. 18(5):594-601: "Alpha-lipoic acid treatment showed small, yet significant short-term weight loss compared with placebo."

Notes: "Altogether, LA seems to have a clinically relevant glucose lowering effect, but evidence supporting its use towards weight loss are still of low-quality. Its supplementation may be considered for the treatment of obesity, especially when T2D coexists, under the supervision of experienced health professionals, given the possible side effects that have been reported" (Watanabe et al. 2020. Op. cit.).

Litramine - "a commercially available proprietary product containing a natural fibre complex derived from prickly pear cactus (Opuntia ficus-indica) with added soluble fibre from Acacia species, co-processed with cyclodextrin" (Bessell et al. 2021. Int J Obes.45(8):1631-43).

Review: Bessell et al. 2021. Op. cit.: "The two RCTs reported statistically significant weight changes (-2.4 kg and -2.24 kg) compared to placebo, however, these mean differences were below our benchmark of -2.5 kg weight loss for clinical significance."

Mangosteen (Garcinia mangostana)

Presumed mechanism of action: "The main compounds are mangostins and isoprenylated xanthones...In vitro studies have shown that alpha-mangostin acts as a strong inhibitor of pancreatic lipase, not different from the weight loss medication orlistat. This compound was also reported to induce apoptosis of preadipocytes and enhance lipolysis through the inhibition of fatty acid synthase. In rodent models, mangosteen supplementation led to a glucose lowering effect that could likely be due to hyperplasia of pancreatic beta cells and alpha glucosidase activity. Moreover, alpha-mangostin treated diet induced obesity mice experienced weight loss, improved glucose and lipid profile and reduced liver fat accumulation through a Peroxisome proliferator-activated receptor gamma and SIRT-1-AMPK pathway" (Watanabe et al. 2020. Nutrients. 12:2873).

Possible adverse effects: “Mangosteen is possibly safe when taken for up to 12 weeks. It might cause constipation, bloating, nausea, vomiting, and tiredness” (WebMD 2020. Mangosteen - uses, side effects, and more).

Notes: "Considering the promising but scanty and low-quality evidence, mangosteen should not be encouraged nor recommended against as a treatment of obesity and its complications such as insulin resistance..." (Watanabe et al. 2020. Op. cit.).

N-Oleoyl phosphatidylcholine (NOPE) - "a naturally occurring phospholipid found in many foods of plant and animal origin, including soy and eggs. In the human digestive tract, it is metabolised into the fatty acid oleoylethanolamide (OEA)" (Bessell et al. 2021. Int J Obes.45(8):1631-43). A commercial product, PhosphLEAN, contains NOPE plus epigallocatechin gallate (EGCG), a component of green tea.

Review: Bessell et al. 2021. Op. cit.: "The two RCTs of NOPE/EGCG reported no statistically significant weight difference between the treatment and placebo groups, while the RCT of OEA reported a statistically but not clinically significant weight loss."

Okinawan Flat Belly Tonic - contains EGCG, piperine, inulin, Hibiscus sabdariffa, antioxidant fruits, abonia berry, acai berry, mulberry, and Momordica charantia. "It also contains a vitamin and mineral blend (with over 80 minerals), a metabolic boosting blend with Shilajit extract (an Ayurvedic substance found in Himalayan rocks), a polyphenol blend with 25 potent antioxidants and plant extracts, and a digestive support blend with probiotics and prebiotics" (Hall 2021 May 25. Okinawan Flat Belly Tonic. Science-Based Medicine blog).

Presumed mechanism of action: "It allegedly targets the root cause of weight gain: elevated levels of inflammatory molecules known as C-reactive protein (CRP). When CRP goes up, the fat-burning hormone adiponectin is blocked. The product is claimed to expel CRP and to have many benefits besides weight loss: fewer food cravings, lower stress levels, lower bad cholesterol levels, improved mental clarity, increased energy and vitality levels, improved self-esteem, hormonal equilibrium, and even increased libido" (Ibid.).

Notes: "They claim to have scientific studies to support their claims, but it consists of sparse pickings for some of the individual ingredients. The product itself has never been scientifically tested. The rationale for taking the tonic before 10 AM is never explained" (Ibid.).

Phaseolus vulgaris - see white kidney bean

Phenylpropanolamine - “In the United States, PPA is no longer sold due to an increased risk of haemorrhagic stroke” (Wikipedia 2022. Phenylpropanolamine). In some other countries it is available over the counter or by prescription.

Presumed mechanism of action: "Phenylpropylamine is similar in structure to amphetamine and ephedrine and may act as an appetite suppressant to induce weight loss. It is believed to act via the alpha-1 adrenergic receptor" (Batsis et al. 2021. Obesity. 29(7):1102-13).

Possible adverse effects: “Dizziness, headache, loss of appetite, nausea, dry mouth, restlessness, or trouble sleeping may occur... irregular heartbeat, vision problems, rash, nervousness, increased nasal congestion” (MedicineNet 2022. Phenylpropanolamine - oral, Accutrim, Dexatrim). Other more serious side effects are also possible, including hemorrhagic stroke.

Review: Batsis et al. 2021. Op. cit.: "Five RCTs (published between 1982 and 1999) investigated it. Only one trial was categorized as having a low degree of bias for all categories...Only one study did not report the differences at follow-up between both arms. Three studies demonstrated significant differences between arms, and the remaining did not report on significance. The one high-quality study (low risk of bias) did not demonstrate significant changes in weight between groups at follow-up."

Polyglucosamine - see chitosan

Probiotics - live microorganisms ingested for health benefits. See SUPPLEMENTS PART 2 for uses other than for obesity.

Presumed mechanism of action: alterations in the intestinal microbiota may play a contributing factor in several metabolic problems, including obesity; thus, the intent is to create a healthier distribution of intestinal bacteria.

Possible adverse effects: “Side effects of probiotics are usually minor and consist of self-limited gastrointestinal symptoms, such as gas. In a few cases, mainly involving individuals who were severely ill or immunocompromised, the use of probiotics has been linked to bacteremia, fungemia (fungi in the blood), or infections that result in severe illness" (NIH Office of Dietary Supplements 2020. Probiotics).

Review: Pontes et al. 2021. Clin Nutr. 40(8):4915-31: "The present meta-analysis suggests that probiotics consumption may be helpful for improving body weight, body adiposity and some CVD risk markers in individuals with overweight and obesity."

Psyllium - "a water-soluble fiber derived from the husks of seeds from Plantago ovata" (Watanabe et al. 2020. Nutrients. 12:2873).

Presumed mechanism of action: "A soluble fiber has the ability to dissolve in water, forming a viscous gel that may decrease appetite by occupying the stomach and it may interfere with the absorption of carbohydrates, lipids and bile acids. Some evidence suggests that psyllium may be capable of lowering serum lipids, delaying gastric emptying, improving glycemic control, and promoting satiety inhibition of carbohydrate absorption, delayed gastric emptying, induction of satiety" (Ibid.).

Possible adverse effects: gastrointestinal discomfort, allergic reactions. Can interfere with absorption of some drugs and nutrients.

Reviews:

Jane et al. 2019. Nutrition. 57:84-91: "The results show that the addition of a soluble fiber product, most notably psyllium, improves blood lipid profiles, particularly total and low-density lipoprotein cholesterol, as well as glycemic response, and increases satiety, and by thus improving MetS and CVD risk factors, may augment the processes initiated by weight reduction diets."
Wharton et al. 2020. Crit Rev Food Sci Nutr. 60(10):1614-30: "There was insufficient evidence to suggest that the natural supplements examined [which included psyllium] contribute to significant weight loss, with the exception of perhaps glucomannan..."
Xiao et al. 2020. Phytother Res. 34(6):1237-47 [diabetic patients]: "There was no significant change in high-density lipoprotein, body mass index, cholesterol, and weight."
Darooghegi Mofrad et al. 2020. Crit Rev Food Sci Nutr. 60(5):859-72: "Psyllium supplementation does not reduce body weight, BMI, and WC significantly."
Bessell et al. 2021. Int J Obes.45(8):1631-43: Two randomized controlled trials were identified; "Neither RCT reported a statistically significant weight change compared to placebo."

Notes: "Overall, the quality of evidence in literature evaluating the effects of psyllium consumption on weight loss is low and limited by the great heterogeneity between different studies in terms of duration, design, type of intervention, and dose utilized. Therefore, the use of psyllium supplementation for inducing weight loss cannot be recommended at the moment" (Watanabe et al. 2020. Op. cit.).

Pyruvate - part of normal human metabolism, not required in the diet.

Presumed mechanism of action: "Its mechanism of action is unclear and only partially studied. It has been proposed that pyruvate may induce the shift in substrate utilization from predominantly carbohydrate to predominantly fat following pyruvate consumption, which may in turn contribute to increase fat oxidation, a mechanism to which both lower insulin levels and higher acetylCoA concentrations may contribute to” (Watanabe et al. 2020. Nutrients. 12:2873). "Pyruvate has been proposed to aid with lipid metabolism through reversible conversion to phosphoenolpyruvate and to increase glucose uptake by skeletal muscles, providing a potential for weight loss" (Batsis et al. 2021. Obesity. 29(7):1102-13).

Possible adverse effects: “Side effects such as stomach upset, gas, bloating, and diarrhea can occur when large amounts are taken” (WebMD 2020. Pyruvate - uses, side effects, and more).

Reviews:

Onakpoya et al. 2014. Crit Rev Food Sci Nutr. 54(1):17-23: "The evidence from randomized clinical trials does not convincingly show that pyruvate is efficacious in reducing body weight."
Batsis et al. 2021. Op. cit.: "There were seven RCTs published between 1992 and 2009, none of which were categorized as having an overall low degree of bias...Two studies did not report differences between arms, whereas the authors considered four studies to be statistically significant."

Notes: "Given the lack of recent data and the low-quality of evidence in literature, pyruvate consumption should not be encouraged as a tool for inducing weight loss" (Watanabe et al. 2020. Op. cit.).

Raspberry ketone - "Raspberry ketone (4-(4-hydroxyphenyl)-2-butanone) is the key flavour of raspberries and has for a long time been widely used by the food industry as flavouring substance and for other purposes in perfumery and cosmetics. In the last few years, raspberry ketone has been sold as an ingredient in food supplements where it has been claimed to have a slimming effect" (Bredsdorff et al. 2015. Regul Toxicol Pharmacol. 73(1):196-200).

Presumed mechanism of action: "Raspberry ketones affect the metabolism through two mechanisms by increasing the levels of two hormones, norepinephrine and adiponectin. Increasing the norepinephrine causes the body's temperature to rise, causing the body to burn more fat. 'Raspberry ketones also increase levels of adiponectin, which is a hormone that helps with lowering glucose levels,' explains Dr. Sarah G. Khan, DietsInReview.com's resident pharmacist. 'The less circulating glucose, the less likely it will be converted into a stored energy source like glycogen. Adiponectin is found least frequently in obese people and may have a possible role to play in insulin resistance and diabetes. In other words, raspberry ketone is a stimulant, like so many other weight loss supplements'" (Badore 2012 Feb 13. Dr. Oz sparks debate about raspberry ketone supplements. Yahoo).

Possible adverse effects: In the amounts contained in raspberries and food flavorings, raspberry ketone is generally recognized as safe. However, the much larger amounts in weight loss supplements raise safety concerns. "It may increase heart rate and affect blood pressure. As well, Dr. Khan cautions of the raspberry ketone side effects that could impact the thyroid. Other common side effects of stimulants include difficulty sleeping and agitation. Additionally, Dr. Khan says that the supplement may interact with a number of different medications, and would not recommend the supplement to anyone with diabetes, high blood pressure, asthma or who is taking antidepressants: (Badore 2012. Op. cit.). "Investigations of raspberry ketone in quantitative structure-activity relationship (QSAR) models indicated potential cardiotoxic effects and potential effects on reproduction/development" (Bredsdorff et al. 2015. Op. cit.).

Notes: "The research behind the claims that raspberry ketones help with weight loss is scant. There have been two small studies showing laboratory mice are less likely to gain weight when adding raspberry ketones to their diet. However, there have been no placebo-controlled studies of humans" (Badore 2012. Op. cit.).

Resveratrol - a compound found in grapes and some other plants. See SUPPLEMENTS PART 2 for a detailed discussion.

Presumed mechanism of action: "Resveratrol has been found to be one of the strongest activators of SIRT-1 through an AMPK mediated mechanism...In preclinical studies, resveratrol was found to protect against metabolic disease and weight gain in diet induced obesity models. Moreover, its supplementation led to decreased adipogenesis and viability in preadipocytes and increased lipolysis and reduced lipogenesis in mature adipocytes" (Watanabe et al. 2020. Nutrients. 12:2873).

Possible adverse effects: possible allergic reactions if allergic to grapes or wine; interactions with some drugs

Review: Tabrizi et al. 2020. Crit Rev Food Sci Nutr. 60(3):375-90: "Overall, the current meta-analysis demonstrated that resveratrol intake significantly reduced weight, BMI, WC and fat mass, and significantly increased lean mass, but did not affect leptin and adiponectin levels."

Notes: "Altogether, studies supporting the use of Resveratrol as an anti-obesity drug are of low-quality, and the clinical relevance of its effects is uncertain. It could be however taken into consideration when associated to other weight loss interventions, given the strong preclinical evidence, the virtual absence of reported side effects and its small effect in weight reduction" (Watanabe et al. 2020. Op. cit.).

Spirulina ("blue-green algae") - "Blue-green algae" are not actually algae but are cyanobacteria. "Spirulina" is both the name of a genus of cyanobacteria (later divided into Spirulina and Arthrospira), as well as a term used to refer to the dried biomass of two species, A. platensis and A. maxima. See also discussion in SUPPLEMENTS PART 2.

Presumed mechanism of action: "The role of spirulina on body weight control is not fully elucidated yet. In murine models, spirulina extracts administration showed anti-obesity and lipids-lowering effects, mediated by different mechanisms, such as adipogenesis suppression, browning of white adipose tissue, and modification in brain and liver genes expression. In humans, it proved effective in decreasing appetite" (Watanabe et al. 2020. Nutrients. 12:2873).

Possible adverse effects: "Blue-green algae products that are free of contaminants, such as liver-damaging substances called microcystins, toxic metals, and harmful bacteria, are POSSIBLY SAFE for most people when used short-term...But blue-green algae products that are contaminated are POSSIBLY UNSAFE. Contaminated blue-green algae can cause liver damage, stomach pain, nausea, vomiting, weakness, thirst, rapid heartbeat, shock, and death. Don't use any blue-green algae product that hasn't been tested and found to be free of microcystins and other contamination...Blue-green algae are POSSIBLY UNSAFE for children. Children are more sensitive to contaminated blue-green algae products than adults" (MedlinePlus 2021. Blue-green algae). Contamination with insect parts is possible. May slow blood clotting and affect blood glucose levels. There are interactions with some medications.

Reviews:

Moradi et al. 2019. Complement Ther Med. 47:102211: "Spirulina supplementation significantly reduces body weight, especially in obese individuals."
Zarezadeh et al. 2021. Phytother Res. 35(2):577-86: "Spirulina supplementation exerts beneficial effects on weight and waist circumference."

Notes: "Overall, despite its promising effects described in animal models, evidence supporting the use of Spirulina for weight loss purposes in humans is scarce, controversial and of low quality. Its supplementation should therefore not be recommended as a treatment for obesity at this time" (Watanabe et al. 2020. Op. cit.).

Starch blockers - see also white kidney bean

Presumed mechanism of action: inhibitors of amylase, which digests starch.

Possible adverse effects: "In some early studies, ingesting CHO blockers led to gas and bloating. However, Boivin reported that this could be ameliorated with proper dosing" (Preuss 2009. J Am Coll Nutr. 28(3):266-76).

Synephrine - see bitter orange

Thermogenic supplements (fat burners) - claim to increase body's metabolism and consume calories apart from the need to do muscular work. Since energy is conserved, calories used without producing work are released as heat, so the compounds would be "thermogenic." "Overall, these pills have utilized active ingredients that were almost always sympathomimetic in chemical signature. Early on the predominant active substance in the supplements stemmed from ephedra alkaloids (EA), followed by a combination of EA with caffeine, while more recently active substances have included synephrine, caffeine, caffeine anhydride (CA), ephedra extracts that are alkaloid free, chlorogenic acid or Epigallocatechin gallate (EGCG) alone or some combination of various active ingredients" (Clark and Welch 2021. Nutr Health. 27(4):445-59).

Presumed mechanism of action: "The purported benefit metabolically may be through sympathomimetic induction of greater lipolysis and possible upregulation of uncoupling proteins to induce a thermogenic effect" (Ibid.).

Possible adverse effects: "We must also draw attention to the ever-growing reports of adverse effects and negative outcomes from the use of purported fat burner dietary supplements. This list of adverse and negative outcomes includes reports related to issues of Rhabdomyolysis, ischemic stroke, and sudden cardiac death stemming from the use of this type of dietary supplement in conjunction with diet and exercise. Additionally, and previously noted, are the reports of hepatic and renal issues that are associated with the use of sympathomimetic dietary supplements. More troubling are the various reports of psychiatric, cognitive, and sleep disturbances associated with the use of thermogenic and fat-burner substances...Tolerance [see below] necessitates possibly ever-increasing dosages of the pharmacological agent and given that supplements are poorly regulated substances, there is an increased risk of adverse events. This issue is compounded based on the common adage used by consumers of most dietary supplements: if some is of benefit, more must be better" (Ibid.).

Review: Clark and Welch 2021. Op. cit.: "Chi-square comparison to exercise, or combination of diet and exercise, indicates that responses induced from weight-loss supplements were less effective than what is obtained from utilizing exercise, or diet and exercise, without additional weight-loss supplements. Conclusion: There appears to be limited benefit that may be derived from the inclusion of thermogenic dietary supplements to reduce body mass and improve cardiometabolic health for individuals who are overfat."

Notes: Clark and Welch (2021. Op. cit.) made the following points:

"Most studies associated with such substances examine solely acute responses to an exercise session, whereas the time necessary to induce weight loss and improve health status requires prolonged alteration to lifestyle, i.e. significant changes in both diet and addition of exercise to activities of daily living, that goes well beyond the time for many of the acute studies. There is also the means by which having an effect is confused with level of effectiveness. Where single study reports may indicate that treatment induced a change that would be significant from the baseline measures, when compared relative to the population norms (i.e. standard deviation), the determined effect size does not support that indication of significance."
"Moreover, there is also a need to stipulate that pharmacologically speaking, extended use of sympathomimetic supplements, as with any medicinal substance, may wane in responsiveness and benefits with prolonged use. This reduced effectiveness is most likely due to alteration of receptors on cells where the drug is interacting. A large portion of this argument goes well beyond what has been analyzed here. Nonetheless, it must be made, especially in light of the intended question about long-duration use of such supplements for achieving weight loss for individuals who are overfat, an issue that to date unfortunately cannot be addressed, as few studies examine dose responses for use of these substances over a duration greater than 8 weeks."
"Alarmingly, the action of the dietary supplements should allow for an increased metabolic rate, yet chronic use appears to induce a reduced metabolic rate."

Usnic acid - a chemical produced by lichens

Presumed mechanism of action: uncoupler of oxidative phosphorylation, leading to calories being consumed without exercise.

Possible adverse effects: liver damage has been reported. "At least 21 incident reports of severe liver toxicity related to the intake of the dietary supplement LipoKinetix, containing sodium usniate, were received by the US Food and Drug Administration (US FDA) between 2001 and 2005. These cases included one death, one liver transplant, seven liver failures, ten chemical-induced hepatitides, and several cases of mild hepatic toxicities" (Kwong and Wang 2020. Environ Toxicol Pharmacol. 80:103493).

Notes: “There are no adequate or well-controlled trials to substantiate any claims of effectiveness in humans for any indication” (Yellapu et al. 2011. Can J Gastroenterol. 25(3):157-60).

Whey protein - "Whey protein (WP) is the water-soluble part of milk and it is considered to be a high biological value protein, including all essential 22 amino acids" (Watanabe et al. 2020. Nutrients. 12:2873).

Presumed mechanism of action: "Consumption of WP has been shown to increase circulating concentrations of satiety hormones of the lower gut, including GLP-1 and PYY thus suppressing appetite more than other proteins, such as casein, soy, and egg albumin. Moreover, WP may promote fat mass reduction through its oxidation, with concomitant preservation of lean mass" (Ibid.).

Possible adverse effects: problems if allergic to dairy products; interactions with some drugs

Review: Miller et al. 2014. J Am Coll Nutr. 33(2):163-75: "The current body of literature supports the use of WP, either as a supplement combined with resistance exercise or as part of a weight loss or weight maintenance diet, to improve body composition parameters."

Notes: "In conclusion, evidence supporting the use of WP 100–600 g/week, either as a supplement combined with resistance exercise or as part of a dietary restriction program in order to improve body composition parameters, is of moderate quality, but further dose/response trials should be performed. Overall, WP supplementation may be recommended for the treatment of obesity" (Watanabe et al. 2020. Op. cit.).

White kidney bean (Phaseolus vulgaris)

Presumed mechanism of action: amylase inhibition

Possible adverse effects: toxicity of lectin (extracts may be safe)

Reviews:

Udani et al. 2018. Foods. 7(4):63: "This meta-analysis found statistically significant effects of Phaseolus vulgaris supplementation on body weight and body fat."
Batsis et al. 2021. Obesity. 29(7):1102-13: "Seven RCTs identified it between 2007 and 2014. However, none of these studies fulfilled criteria for low risk of bias across each category...Three studies reported significant weight loss compared with placebo, whereas three did not report such statistical changes."

Notes: "The evidence supporting the use of PVE [Phaseolus vulgaris extracts] 1 to 3 g/day for weight loss, and especially that of Phase 2® products, is of moderate quality, and its efficacy was demonstrated of sufficient clinical importance. PVE supplementation could be encouraged as a tool for weight loss" (Watanabe et al. 2020. Nutrients. 12:2873)."

Zantrex-3

Presumed mechanism of action: contains caffeine, green tea, and several herbs that act as stimulants.

Possible adverse effects: see adverse effects of caffeine above. High levels of caffeine taken before exercise may be dangerous for some people.

OTHER APPROACHES

Acupuncture - see Eastern Part 1 for a discussion of acupuncture. In general, acupuncture shows little or no benefit compared to sham acupuncture, indicating benefits are placebo effects. Moreover, most studies originate from China, and cannot be considered reliable (almost every study originating in China reports positive results). Concerning acupuncture for weight loss, Esteghamati et al. (2015. Int J Endocrinol Metab. 13(2):e19678) wrote, "Studies on animals and humans indicate a number of possible mechanisms, by which acupuncture contributes to weight reduction. First, it is suggested that acupuncture can regulate obesity-related neuropeptides in the central nervous system, as well as fat depot derived adipokines. Second, acupuncture may be involved in the regulation of hypothalamus-pituitary-adrenal cortex and sympathetic-adrenal cortex axis. Third, a number of studies have observed a reduction in triglycerides, LDL, and total cholesterol with acupuncture and thereby might exert lipid lowering effects. Fourth, since high levels of bacteroides have been observed in obese patients, one of the weight loss mechanisms of abdominal acupuncture may involve the reduction of bacteroides...In summary, the shortcomings observed in the available literature on acupuncture are manifold. To begin, several studies draw their conclusions from uncontrolled trials. Additionally, studies with controlled trial designs are riddled with flaws, as they suffer from methodological weaknesses, such as limited durations of follow up, absence of placebo control groups, loosely observed protocols, and arbitrary selection of acupoints..." Batsis et al. (2021. Obesity. 29(7):1102-13) noted that “The two studies demonstrating a low risk of bias either did not report the differences between the arms or were not significant.”

Body wraps - cause temporary weight loss through sweat. “The majority of evidence that exists comes directly from the companies that market these wraps. There’s very little - if any - unbiased research or studies about the effectiveness of body wraps for weight loss” (Healthline 2018. Will using a body wrap help me lose weight?). There is danger of dehydration and overheating.

Diet patches containing homeopathic medicines - see Holistic Part 1 for a discussion of homeopathy. Any product that is truly homeopathic contains no molecules of active ingredients and therefore cannot have any effects.

Ear stapling - insertion of staples at acupuncture points in the ear. These are left in place for days or even months. It is based on alleged effects of stimulating acupuncture points on hunger. Acupuncture is discussed in Eastern Part 1. In general, the premises of acupuncture are unscientific, and there is no good evidence that acupuncture provides benefits beyond placebo for any condition.

Electrical muscle stimulation (EMS) - has a legitimate medical use (physical therapy, prevention of muscle atrophy, etc.), but there is no evidence that it can help weight loss. FTC took action against some marketers in 2005.

Lipodissolve - "involves several injections that supposedly dissolve and remove small pockets of fat from areas of the body. Lipodissolve is also known as mesotherapy, lipozap, lipotherapy, or injection lipolysis. The drugs most often used are combinations of phosphatidylcholine and deoxycholate. Sometimes other ingredients such as vitamins, minerals and herbal extracts are added into the mix..." (Reinberg 2010 Apr 17. FDA issues warning on "fat-melting" spa injections. HealthDay). The FDA issued warnings in 2010, stating that the claims were unsubstantiated and there were reported side effects, including permanent scarring.

Mesotherapy - see lipodissolve

Mind-body medicine - "Mind-body interventions that were evaluated for weight loss efficacy included behavioral therapies (e.g., mindfulness, stress management), hypnosis, meditation, and massage. In general, these strategies are designed to target maladaptive food behaviors such as cravings and hedonic eating. Of the 22 RCTs conducted between 1980 and 2017, only 2 (9%) were classified as having a low risk of bias. Only six (27%) studies reported significant findings for greater weight loss compared with control. Two studies with a low risk of bias did not report pre/post intragroup differences in weight change" (Batsis et al. 2021. Obesity. 29(7):1102-13).

Non-invasive body contouring - "Invasive body-contouring refers to the surgical removal of localized areas of adiposity from under the skin. Liposuction is the most common cosmetic plastic surgery procedure used around the world. However, this popular method still raises serious concerns about the safety of its invasive nature. Possible complications, resulting from the invasive procedure, range in severity from prolonged swelling, bruising, and numbness, to thrombophlebitis and pulmonary embolism. A pressing need for safer procedures, with faster recovery time, as well as smaller number of side effects, therefore, makes non-invasive body contouring techniques perhaps several of the most appealing and fastest growing extents of esthetic surgery today" (Esteghamati et al. 2015. Int J Endocrinol Metab. 13(2):e19678). Among these techniques are (quotes from Esteghamati et al. 2015. Op. cit.):

High intensity focused ultrasound - "used for the ablation of subcutaneous fat tissue. Mechanisms by which HIFU affects the fat depot include hyperthermia, whereby a coagulative necrosis of certain areas is brought about with no harm to adjacent areas, and cavitation formation, which exerts high degrees of heat and pressure in the microenvironment, therefore subjecting the adipose tissue to mechanical damage."
Low level laser therapy - "Low Level Laser Therapy (LLLT) is another non-invasive body contouring method, which has yielded successful results in fat reduction of localized areas, such as the hips, waist, thighs, and upper arms. The mechanism of action of LLLT is open to investigation. According to one narrative, by forming temporary pores in the adipocytes’ membrane, LLLT triggers the release of intracellular lipid for additional metabolization...Despite these preliminary findings, suggestive of the efficacy of the method, further research into LLLT is required to fully appreciate its cellular and systemic effects, and to ascertain treatment protocols, which allow the highest degree of safety and effectiveness possible."
Cryolipolysis - " an emergent technology which targets fat selectively through controlled cooling...a 2009 review of four clinical studies concluded that there was sufficient evidence to support the efficacy and safety of cryolipolysis, as a noninvasive fat reduction procedure, even though its mechanism of action is yet to be explained."
Radiofrequency - "The mechanism of action of RF is based on thermal alteration of the dermal/hypodermal layers. Increasing tissue temperature raises vascular perfusion, resulting in lipid turnover secondary to the increased oxygen content. Increased lipid turnover eventually leads to fat cell shrinkage, and circumferential reduction...there are many articles to support the clinical efficacy and safety of using RF."

"Non-invasive body contouring techniques are generally regarded as safe. By far, the most critical issue concerning these methods is patient dissatisfaction. Non-invasive body contouring only results in moderate reductions of 2 to 4 cm in limb or waist circumference. Therefore, their efficacy in morbidly obese patients is fairly limited. At present, there are no systematic evaluations of the non-invasive methods used in body contouring or subcutaneous fat reduction, in terms of efficacy, safety, and patient satisfaction. Carrying out more sophisticated outcome studies, in the form of systematic reviews and meta-analyses, is essential to offer proof of the value of non-invasive body contouring" (Ibid.).

Whole body vibration - "'Whole-body vibration (WBV) is a form of physical training in which very quick vertical oscillations are applied to the whole body, generally by standing on a WBV platform,' reports Patrick Jacobs, PhD, exercise scientist" (Pritzker 2022 Jan 24. Will a vibration machine help me lose weight? Verywell Fit). Use for purposes other than weight loss is discussed in the article on chelation therapy and other miscellaneous approaches.

"When it comes to weight loss and WBV, the evidence is inconclusive. More research is needed with larger participant numbers to identify the relationship between WBV and weight loss. While so many other physical benefits come from WBV training, one study determined that the results of 6 to 24 weeks of WBV training had no significant effect on percent body fat. On the other hand, another review [Alavinia et al. 2021. Disabil Rehabil. 43(14):1935-47] found benefits for reducing body fat in patients with obesity, especially when combined with traditional measures for weight loss. They determined that using WBV therapy alongside conventional weight management strategies could increase reductions in fat mass" (Ibid.).

REFERENCES

See also references for review articles in the text.

Diets and weight loss - general

Berg FM. 1995. Health risks of weight loss (pdf file of 167 page book)

St Jeor ST, Howard BV, Prewitt TE, Bovee V, Bazzarre T, Eckel RH; Nutrition Committee of the Council on Nutrition, Physical Activity, and Metabolism of the American Heart Association. 2001. Dietary protein and weight reduction: a statement for healthcare professionals from the Nutrition Committee of the Council on Nutrition, Physical Activity, and Metabolism of the American Heart Association. Circulation. 104(15):1869-74

Barrett S. 2003. Impossible weight-loss claims: summary of an FTC report. Quackwatch

Esteghamati A, Mazaheri T, Vahidi Rad M, Noshad S. 2015. Complementary and alternative medicine for the treatment of obesity: a critical review. Int J Endocrinol Metab. 13(2):e19678

Ernst E. 2020 Apr 13. Dangerous nutritional advice in 100 best-selling books. Edzard Ernst [see next item]

Marton, RM, Wang, X, Barabási, AL, Ioannidis JPA. 2020. Science, advocacy, and quackery in nutritional books: an analysis of conflicting advice and purported claims of nutritional best-sellers. Palgrave Commun 6:43

Hall H. 2021 Apr 13. Lose weight without diet or exercise? Where's the proof? Science-Based Medicine

Hale J. 2021 Sep 15. Examining common obesity myths. Center for Inquiry

Tiller N. 2021 Nov 18. Diets, detox, and other delusions. Skeptical Inquirer

Hale J. 2022 Jan 10. Don't fall for New Year's fitness and health myths. Center for Inquiry

Diets - multiple

Leung B, Lauche R, Leach M, Zhang Y, Cramer H, Sibbritt D. 2018. Special diets in modern America: analysis of the 2012 National Health Interview Survey data. Nutr Health. 24(1):11-8 [abstract]

Johnston BC, Kanters S, Bandayrel K, Wu P, Naji F et al. 2014. Comparison of weight loss among named diet programs in overweight and obese adults: a meta-analysis. JAMA. 312(9):923-33

WebMD. Weight loss & diet plans A-Z

Diets - specific

Mayo Clinic Staff. 2022 May 12. Atkins Diet: What's behind the claims? Mayo Clinic

Reshanov 2014 Jan 20. Still no evidence for blood-type diet. EarthSky [see next item]

Wang J, García-Bailo B, Nielsen DE, El-Sohemy A. 2014. ABO genotype, 'blood-type' diet and cardiometabolic risk factors. PLoS One. 9(1):e84749

Hall H. 2021 Oct 12. Blue Zones Diet: speculation based on misinformation. Science-Based Medicine

Mayo Clinic Staff. 2021 June 25. DASH diet: Healthy eating to lower your blood pressure. Mayo Clinic

Jones T. 2021 14 Oct. Does food combining work? Healthline

Gavura S. 2021 May 27. Can GMOs cause gastrointestinal sensitivity and inflammation? Science-Based Medicine

Gaesser GA, Angadi SS. 2012. Gluten-free diet: imprudent dietary advice for the general population? J Acad Nutr Diet. 112(9):1330-3

Anon. 2015 Feb 27. Wheat Belly arguments are based on shaky science, critics say. CBC News

Reilly NR. 2016. The gluten-free diet: recognizing fact, fiction, and fad. J Pediatr. 175:206-10

Novella S. 2019 Aug 28. Gluten update. Science-Based Medicine

Boyer G, Caulfield T, Green PHR, Lebwohl B. 2019. Promotion of testing for celiac disease and the gluten-free diet among complementary and alternative medicine practitioners. Am J Gastroenterol. 114(5):786-791 [abstract]

Hall H. 2020 Aug 18. The Hallelujah Diet. Science-Based Medicine

Wallis C. 2020 Sep 1. How good a diet is intermittent fasting? Scientific American

Joshi S, Ostfeld RJ, McMacken M. 2019. The ketogenic diet for obesity and diabetes - enthusiasm outpaces evidence. JAMA Intern Med. 179(9):1163-4 [first paragraph]

Ernst E. 2020 Sep 16. "Keto-flu" - a side-effect of a popular diet. Edzard Ernst

Campbell TC and Campbell T. 2017 Aug 23. "The Plant Paradox" by Steven Gundry MD - a commentary. T. Colin Campbell Center for Nutrition Studies [lectins]

Astrup A, Meinert Larsen T, Harper A. 2004. Atkins and other low-carbohydrate diets: hoax or an effective tool for weight loss? Lancet. 364(9437):897-9 [abstract]

Barrett S. 2008. Low-carbohydrate diets. Quackwatch

Neale T. 2012 Jun 27. Low carb-high protein diets may put heart at risk. MedPage Today

Kirkpatrick CF, Bolick JP, Kris-Etherton PM, Sikand G, Aspry KE et al. 2019. Review of current evidence and clinical recommendations on the effects of low-carbohydrate and very-low-carbohydrate (including ketogenic) diets for the management of body weight and other cardiometabolic risk factors: A scientific statement from the National Lipid Association Nutrition and Lifestyle Task Force. J Clin Lipidol. 13(5):689-711

Rogers MK. 2022. Macrobiotic diet. WebMD

Hall H. 2020 Oct 20. The McDougall Diet. Science-Based Medicine

Barrett S. 2022. A close look at the NutriMost Fat Loss System. Chirobase

Hall H. 2022 Jan 4. Eat for Life: Joel Fuhrman's Nutritarian Diet. Science-Based Medicine

Nella A. 2022 Apr 27. Paleo diet: What it is and why it's not for everyone. Good Food is Good Medicine

Zelman KM (ed). 2021. All about the paleo diet. WebMD

Pagán CN. 2021. Pritikin diet. WebMD

Anon. 2020. Pritikin diet review: benefits, downsides, and more. Healthline

Gorski D. 2015 Jul 15. Penn Jillette interviews water fast guru Dr. Michael Klaper. Woo ensures. Respectful Insolence

Anon. 2017. The Zone Diet: a complete overview. Healthline

Weight loss supplement: adverse effects (see also individual products below)

Yellapu RK, Mittal V, Grewal P, Fiel M, Schiano T. 2011. Acute liver failure caused by “fat burners” and dietary supplements: a case report and literature review. Can J Gastroenterol. 25(3):157-60

Eichner S, Maguire M, Shea LA, Fete MG. 2016. Banned and discouraged-use ingredients found in weight loss supplements. J Am Pharm Assoc. 56(5):538-43

Kaplan S. 2016 Apr 4. Popular weight loss supplements contain controversial stimulant, FDA warns. STAT

Multiple supplements

Pittler MH, Ernst E. 2004. Dietary supplements for body-weight reduction: a systematic review. Am J Clin Nutr. 79(4):529-36

Belluz J, Hoffman SJ. 2013 Jan 1. Dr. Oz’s miracle diet advice is malarkey. Slate

Federal Trade Commission 2014. Gut check: A reference guide for media on spotting false weight loss claims

Vaughan RA, Conn CA, Mermier CM. 2014. Effects of commercially available dietary supplements on resting energy expenditure: a brief report. ISRN Nutr. 2014:650264

Sun NN, Wu TY, Chau CF. 2016. Natural dietary and herbal products in anti-obesity treatment. Molecules. 21(10):1351

Farrington R, Musgrave IF, Byard RW. 2019. Evidence for the efficacy and safety of herbal weight loss preparations. J Integr Med. 17(2):87-92 [abstract and excerpts]

Watanabe M, Risi R, Masi D, Caputi A, Balena A, et al. 2020. Current evidence to propose different food supplements for weight loss: a comprehensive review. Nutrients. 12(9):2873

Bessell E, Maunder A, Lauche R, Adams J, Sainsbury A, Fuller NR. 2021. Efficacy of dietary supplements containing isolated organic compounds for weight loss: a systematic review and meta-analysis of randomised placebo-controlled trials. Int J Obes (Lond). 45(8):1631-43 [abstract]

Batsis JA, Apolzan JW, Bagley PJ, Blunt HB, Divan V et al. 2021. A systematic review of dietary supplements and alternative therapies for weight loss. Obesity.29(7):1102-13

Specific supplements

Center for Science in the Public Interest 2009 Mar 23. CSPI warns consumers about web-based açai scams

Hall H. 2008 Jan 22. Akavar 20/50 and truth in advertising. Science-Based Medicine

Solokas J. 2021 May 21 and Jun 4. Artificial sweeteners - a free lunch, or an obesogenic carcinogen? What 80+ studies say. Science-Based Medicine. Part 1 Part 2

Fugh-Berman A, Myers A. 2004. Citrus aurantium, an ingredient of dietary supplements marketed for weight loss: current status of clinical and basic research. Exp Biol Med (Maywood). 229(8):698-704 [abstract] [bitter orange]

Barrett S. 2000. "Cellulite" removers. Quackwatch

Grundlingh J, Dargan PI, El-Zanfaly M, Wood DM. 2011. 2,4-dinitrophenol (DNP): a weight loss agent with significant acute toxicity and risk of death. J Med Toxicol. 7(3):205-12

Barrett S. 2007. Claims for Enviga challenged. Quackwatch

Hall H. 2013 Dec 24. Garcinia probably works but is far from a weight-loss miracle. Science-Based Medicine

Barrett S. 2004. Stay away from FiberWeigh. Quackwatch [glucomannan]

Gavura S. 2014 Oct 23. Lessons from the dubious rise and inevitable fall of green coffee beans. Science-Based Medicine

Gorski D. 2015 Jan 28. Dr. Oz’s “green coffee bean extract” scammer guest must repay $9 million. Respectful Insolence

Pittler MH, Ernst E. 2001. Guar gum for body weight reduction: meta-analysis of randomized trials. Am J Med. 110(9):724-30 [abstract]

Salahi L. 2011 Dec. 6. FDA, FTC crack down on illegal HCG weight loss products. ABC News [homeopathic HCG products]

Food and Drug Administration. 2020 Jul 13. Avoid dangerous HCG diet products

National Center for Complementary and Integrative Health. 2020. Hoodia

Hall H. 2021 May 25. Okinawan Flat Belly Tonic. Science-Based Medicine

Badore M. 2012 Feb 13. Dr. Oz sparks debate about raspberry ketone supplements. Yahoo

de Ligt M, Timmers S, Schrauwen P. 2015. Resveratrol and obesity: Can resveratrol relieve metabolic disturbances? Biochim Biophys Acta. 1852(6):1137-44

Other approaches

Healthline 2018. Will using a body wrap help me lose weight?

Ernst E. 2018 Dec 18. Laser Lipo: a solution for the obesity epidemic? Edzard Ernst

Pritzker S. 2022 Jan 24. Will a vibration machine help me lose weight? Verywell Fit