What Are The Best Weight Loss Supplements: What Does The Science Say?

With the overweight/obesity pandemic continuing to reach all-time highs here in the U.S., and around the world, more people than ever have become interested in finding effective ways to lose weight.  

While it’s true that nothing is more effective than diet and exercise when it comes to losing weight, many individuals still struggle to achieve the kind of weight loss outcomes they’re after through diet and exercise alone.  

Ultimately, that’s why millions of people looking to lose weight eventually become interested in weight loss supplements.  But with all the different weight loss products out there -- many of which come along with extravagant claims -- it can be difficult to tell what products and ingredients actually work.  

That’s why in this article, we’ll be evaluating the efficacy of 16 different substances commonly found in weight loss products in order to shed more light on what weight loss supplements work best.  

What Are The Best Weight Loss Supplements?

1. 5-HTP

5-Hydroxytryptophan (5-HTP) is an essential amino acid metabolite and a precursor in the body’s production of serotonin, an important hormone and neurotransmitter.  Amongst other things, serotonin is believed to have a regulatory effect on appetite, with some research showing that higher levels may help to stave off food cravings.⁽¹⁾

As such, some researchers have investigated the effects of 5-HTP supplementation on obesity, with numerous studies ultimately demonstrating significant weight loss along with reductions in things like binge eating and daily energy consumption.⁽²⁾⁽³⁾

For example, one double-blind, placebo-controlled study ultimately found that at the end of a 6 week supplementation period, where all study participants followed the same basic diet, those who were given 5-HTP, on average, lost almost 9 lbs, compared to the placebo group, who saw no changes in body weight at all.⁽⁴⁾

On top of that, the researchers also found that over the course of another 6 week period in which participants diets were not monitored, those who were given 5-HTP saw a significant reduction in their daily carbohydrate intakes and total daily energy intakes, compared to the control group, who saw no such changes. 

The researchers ultimately found that even in the absence of any kind of dietary restrictions, those who took 5-HTP still lost over 4 lbs on average.  

2. Alpha GPC Choline

Alpha GPC choline is a precursor in the body’s production of the important neurotransmitter acetylcholine.  While it plays a number of different physiological roles within the human body, some research suggests that it may help to increase hepatic fat oxidation, which, in turn, may help to improve the weight loss process.  

And indeed, there is ample evidence from animal studies that choline supplementation improves weight loss outcomes in rats and mice.  However, to date, there is only a limited amount of research involving human subjects.  With that being said, most clinical trials involving choline supplementation and weight loss have demonstrated positive results.⁽⁵⁾⁽⁶⁾

For example, one 2014 study examined the effects of choline supplementation on weight loss in judo and taekwondo athletes looking to lose weight rapidly.⁽⁷⁾ The study participants were given either a placebo or a choline supplement twice a day for 1 week.  Both groups consumed a hypocaloric diet and exercised multiple times per week.   

At the conclusion of the study, the researchers ultimately found that study participants who were given choline, on average, lost significantly more weight in comparison to the placebo group.  They also saw greater reductions in body fat percentage and body mass index (BMI). 

3. Bitter Orange Extract (Citrus Aurantium)

Bitter orange extract (BOE), which is technically known as Citrus Aurantium, is derived from the Seville orange and contains the protoalkaloid p-synephrine, which some research suggests may have beneficial effects on the weight loss process.  

In addition to functioning as a thermogenic agent -- thermogenesis is the process through which the body’s resting energy expenditure is increased through the conversion of stored energy into heat -- bitter orange extract is also believed to increase lipolysis, which is the process through which the body breaks down adipose tissue -- AKA fat stores.⁽⁸⁾

To date, there has only been a relatively small number of well-designed human studies involving bitter orange extract and weight loss.⁽⁹⁾ Of those that have been conducted, most have involved products that combine BOE with other ingredients like caffeine and green tea extract, which makes evaluating the efficacy of bitter orange extract a bit more tricky.

With that being said, one double-blind placebo-controlled study published in Current Therapeutic Research recruited overweight adults to participated in a weight-loss study involving a product containing p-synephrine (the central ingredient in bitter orange extract) along with caffeine and salicin.⁽¹⁰⁾

Half of the subjects received a daily dose of the weight loss product containing p-synephrine while the other half received only a placebo.  All subjects consumed a hypocaloric diet and exercised three days per week.  After 8 weeks, the researchers found that compared to the control group, those who received a daily dose of the weight loss product lost significantly more weight (4.5 lb vs. 7 lb).  

In another similar double-blind placebo-controlled study where participants also followed a diet and exercise plan, the research also found that compared to a placebo and control group, those who received a daily dose of a weight loss product containing bitter orange extract (along with caffeine and St John’s wort) lost significantly more weight and body fat.⁽¹¹⁾

4. Caffeine

Caffeine is a psychoactive compound naturally found in coffee and tea leaves.  In addition to helping to improve your mental energy, there is also an ample amount of evidence that caffeine may aid in the weight loss process as well.  

Numerous studies have demonstrated that caffeine helps to increase the body’s resting energy expenditure through thermogenesis and its effects on weight loss have been extremely well-researched, with that vast majority of clinical trials demonstrating significant outcomes.^(12)(13)

 For example, one 2012 study recruited moderately obese adults to participate in a 3-month study examining the effects of caffeine intake on weight loss and maintenance.⁽¹⁴⁾

The researchers ultimately found a significant difference between weight loss in people with high vs low caffeine intakes.  While both groups lost significant amounts of weight -- the average amount of weight loss across both groups was 13 lbs -- the high intake group, on average, saw greater reductions in weight, fat mass, and waist circumference in comparison to the low intake group.    

With that being said, there is some evidence that caffeine intake may hinder insulin-glucose homeostasis, potentially further contributing to insulin resistance in individuals who are overweight/obese.⁽¹⁵⁾

5. Conjugated Linoleic Acid (CLA)

Conjugated Linoleic Acid (CLA), which is a naturally occurring substance found in meat and dairy-based foods, is actually a combination of over 20 different linoleic acid isomers.  

Research suggests that CLA supplementation helps to enhance fatty acid oxidation and increase lipolysis, which again, is the process through which the body breaks down and burns up adipose tissue.⁽¹⁶⁾

And indeed, a number of different preclinical and animal trials have demonstrated significant effects on weight loss.  when it comes to human studies, however, the findings are a little different; while a number of clinical trials have demonstrated statically significant effects on weight loss, those effects were often incredibly small.  

For example, a 2012 systematic review and meta-analysis published in the European Journal of Nutrition evaluated the findings from 7 different randomized clinical trials involving CLA supplementation and weight loss.⁽¹⁷⁾

The researchers ultimately concluded that while there was a small, statistically significant difference in weight loss outcomes observed between CLA and placebo consumption, that difference was so small that the evidence did not convincingly support CLA’s clinical use as a weight-loss supplement.  

6. Forskolin

Forskolin is an extract derived from the Coleusforskohliiplant, which is part of the mint family.  Forskolin has been investigated as a potential weight loss supplement due to its precursory role in the production of hormone-sensitive lipase (HSL), which plays an important role in breaking down triglycerides into free fatty acids that can be burnt up by the body as fuel.⁽¹⁸⁾

Most studies demonstrating positive effects on the weight loss process were conducted using either animals or human tissue.  As of now, only a handful of well-designed human trials have taken place, with most of them examining the effects of forskolin on body composition rather than weight loss.  With that being said, of the studies that have been conducted, most have demonstrated positive outcomes.  

For example, one 12-week double-blind placebo-controlled study involving overweight and obese men ultimately found that those who were given a daily dose of forskolin experienced significant reductions in total body fat mass, while the placebo group experienced no such changes.⁽¹⁹⁾

Additionally, the researchers also observed a significant decrease in the forskolin group’s body fat percentage, with participants seeing an average reduction of about 4% over the course of 12 weeks.  

7. Fucoxanthin 

Fucoxanthin is a naturally occurring marine carotenoid that can be found in several different forms of macroalgae. It’s been investigated as a potential preventative and therapeutic treatment for obesity, with several pre-clinical trials demonstrating that it may help with weight loss in multiple ways.  

First, fucoxanthin appears to activate uncoupling protein-1 expression (UCP1) in white adipose tissue (WAT), which, in turn, stimulates thermogenesis -- i.e. the process through which energy is expended by the body as heat.⁽²⁰⁾ Research suggests that fucoxanthin increases the number of fatty acids that the body ultimately oxides and converts into heat, thus increase the body’s total energy expenditure.⁽²¹⁾

In mouse models, it’s also been shown to positively affect several parameters of metabolic syndrome including blood glucose levels and insulin resistance via the up-regulation of glucose transporters and the down-regulation of insulin-related adipocytokines.⁽²²⁾

While there have been a plethora of animal studies involving fucoxanthin and weight loss, there haven’t been nearly as many studies involving human subjects.  Of the few clinical trials that have been conducted, most have involved the use of fucoxanthin in combination with other substances.  With that being said, some of these trials have demonstrated positive findings.    

For example, one 2009 study ultimately found that over the course of a sixteen‐week, randomized, placebo‐controlled study, those who were given a daily dose of fucoxanthin and pomegranate seed oil on average, saw a 12-pound decrease in weight.⁽²³⁾

On top of that, the researchers also observed that in comparison to the placebo group, participants in the fucoxanthin and pomegranate seed oil group also demonstrated significant increases in resting energy expenditure and reductions in serum triglycerides and liver fat content.  

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8. Garcinia Cambogia

Garcinia Cambogia (GC) is an extract derived from the fruit of a tree sharing the same name.  Some research suggests that it may impact the weight loss process in multiple ways.  On top of potentially helping to increase satiety, some research also suggests that it may have positive effects on things like your glucose, cholesterol, and triglyceride levels as well.⁽²⁴⁾

While the effects of Garcinia Cambogia on weight loss have been well-researched in human trials, to date, there have been mixed findings.  With that being said, some research has demonstrated significant results.

For example, one 2010 review and meta-analysis examining findings from 12 different randomized clinical trials involving Garcinia Cambogia and weight loss ultimately found a small but statistically significant difference in weight loss between those given GC and those given only a placebo, with the GC group losing slightly more weight across the 12 studies included in the review.⁽²⁵⁾

However, several other reviews failed to come to the same conclusion.  For example, a 2008 review that involved 16 different randomized clinal trials ultimately found only one study that demonstrated statistically significant effects on weight loss.⁽²⁶⁾

9. Glucomannan

Glucomannan is a natural dietary fiber derived from the konjac plant as well as from elephant yams.  Some research suggests that it may aid in the weight loss process through the activation of signaling events within the body that help to induce satiety.  However, to date, findings from clinical studies are mixed when it comes to the effects of glucomannan on weight loss.    

Some research involving overweight and obese individuals has demonstrated positive effects on weight loss.  For example, a 2005 critical review published in Alternative Therapies ultimately found 7 different short-term clinical trials involving glucomannan supplementation and weight loss in which study participants lost significant amounts of weight.⁽²⁷⁾

However, several more recent clinical trials involving glucomannan supplementation ultimately failed to find any kind of positive effects on weight loss.  For instance, one 2013 study involving overweight and moderately obese individuals ultimately found that after 8 weeks of supplementation, study particpants ultimately experienced no changes in body weight, body composition or self-reported levels of satiety.⁽²⁸⁾

10. Green Coffee Bean Extract

Green coffee bean extract (GCBE) is unsurprisingly derived from green coffee beans.  In addition to containing caffeine, a known thermogenic agent, it has also been suggested that GCBE may positively impact the weight loss process by altering glucose tolerance and hormone production as well.⁽²⁹⁾

Several well-designed clinical trials have indeed demonstrated significant findings.⁽³⁰⁾ For example, one randomized, placebo-controlled study ultimately found that over the course of 22 weeks, those we received a daily supplement of green coffee bean extract lost an average of 18 lbs, even with no specific dietary modifications in place.⁽³¹⁾

Another 2010 review and meta-analysis involving 3 different randomized clinical trials ultimately found a small but significant association between green tea extract and weight loss across the included studies, leading the researchers to conclude that GCBE may be an effecting weight loss supplement, especially in the short-term.⁽³²⁾

11. Green Tea Extract 

In addition to containing caffeine, green tea extract, which is derived from the leaves of the Camellia Sinesis plant, also contains a natural compound known as epigallocatechin gallate (EGCG).   

Research has demonstrated that EGCG may help to increase your body’s resting energy expenditure through the activation of thermogenesis, which again, refers to the process through which some of the body’s energy stores are converted into heat.⁽³³⁾

And with a large number of clinical trials demonstrating positive findings, there is an ample body of evidence to suggest to green tea extract may be an effective weight loss supplement, especially in the short term.⁽³⁴⁾

For example, one randomized clinical trial examining the effects of green tea supplementation on individuals with metabolic syndrome ultimately found that those who received a daily dose of green tea extract, on average, lost 2.5kg (5.5lbs) and saw a 1.9 point reduction in BMI over the course of the 8 week study period.⁽³⁵⁾

Another 2016 study published in Clinical Nutrition demonstrated similar findings, with those who received a daily dose of green tea extract, ultimately losing an average of  2.4 lbs as well as experiencing a small but significant decrease in BMI over the course of 12 weeks.⁽³⁶⁾ The green tea group also had significantly lower total and LDL cholesterol at the end of the study.

Note: According to the NIH, excessive amounts of EGCG -- one of the main ingredients in green tea extract -- can lead to acute liver injury.⁽³⁷⁾

12. L-Carnitine

L-carnitine is a naturally occurring substance derived from the essential amino acids lysine and methionine.  It plays an important role in the body’s production of energy, helping to transport long-chain fatty acids to be oxidized in the mitochondria of your body’s cells -- the mitochondria help break down nutrients into molecules that can be used by your cells as energy.  

While there have been a number of clinical trials that have investigated the effects of l-carnitine supplementation on weight loss, there have been mixed findings, with some studies ultimately failing to demonstrate any significant outcomes. 

For example, one double-blind placebo-controlled study ultimately found no significant changes in any of the parameters included in the study, including total body weight, fat mass, or resting lipid utilization after 8 weeks of L-carnitine supplementation.  

With that being said several well-designed human studies have indeed demonstrated positive effects on weight.  For example, one 2015 study ultimately observed a 7.38% weight reduction in participants who were administered a daily dose of L-carnitine over an 8-week period.⁽³⁸⁾

A 2016 review ultimately concluded that most clinical evidence suggests that L-carnitine may be an effective weight loss supplement, however, the researchers did observe that the impact on weight loss does appear to decrease over time.⁽³⁹⁾

13. L-Tyrosine

L-tyrosine is a non-essential amino acid naturally produced in small quantities within the human body, however, it’s can also be obtained from consuming animal proteins.  

It’s been demonstrated to increase the rate at which your body produces catecholamines like norepinephrine, which research shows play an important role in regulating your appetite.⁽⁴⁰⁾ More specifically, a spike in norepinephrine production helps to set off a series of signaling events that indicated to your body that you’re satiated, thus reducing the desire to eat.⁽⁴¹⁾

On top of suppressing your appetite, norepinephrine has also been shown to play an important role in lipolysis, which again, is the process through which the body breaks down stored fat (adipose tissue) in order to be used as energy.⁽⁴²⁾ Increasing the body’s production of norepinephrine may ultimately help to mobilize more of your body’s stored fat to be burnt up as energy, especially in combination with a hypocaloric diet and/or exercise.  

While the pre-clinical findings seem promising, few if any randomized clinical trials involving l-tyrosine supplementation have directly investigated weight loss outcomes, which ultimately makes determining its effectiveness as a weight-loss supplement a bit more difficult.  

14. Orlistat (Alli)

Orlistat is an over-the-counter medication commonly sold under the brand name Alli.  It’s been shown to have a positive impact on several parameters related to metabolic syndrome and numerous randomized clinical trials have demonstrated significant effects on weight loss.^(43)(44)

For example, one such trial involving obese adults looked at the effects of orlistat intake over the course of a 2 year period.⁽⁴⁵⁾ In the first year, patients were either given a placebo of a daily dose of orlistat in conjunction with a hypocaloric diet. 

In the second year, some participants who had been previously taking orlistat were switched to a placebo, while others continued to take it.  All test subjects were switched over to a weight maintenance diet.

After the first year, the researches ultimately observed a significantly greater reduction in body weight in the orlistat group, who on average, lost nearly 10 pounds more than the placebo group (the placebo group still lost 13 lbs with just a hypocaloric diet).  

Following the second year when calorie consumption was increased, those who shifted from orlistat to a placebo, on average gained twice as much weight in comparison to those who stayed on it.  Furthermore, patients who changed from taking a placebo in the first year to orlistat in the second actually lost a couple of pounds even in the absence of a calorie restriction.  

15. Raspberry Ketones

Raspberry ketones are an aromatic substance and a central component in the flavoring of raspberries.  Research shows that they may help to decrease the accumulation of lipids and increase the oxidation of fatty acids.  

While some positive effects on weight loss have been observed in animal studies, a limited amount of clinical trials have been conducted.  With that being said, of the few studies that have been carried out, most have demonstrated positive findings.⁽⁴⁶⁾

For instance, in one 2015 study investigating the effects of raspberry ketones on weight loss, the researchers ultimately observed a 5.1% reduction in body fat in individuals who were given a daily dose of raspberry ketones over the course of 12 weeks.⁽⁴⁷⁾

While preliminary findings seem promising, more research needs to be conducted before we can really make any definitive conclusions as to the efficacy of raspberry ketones when it comes to weight loss.  

Should You Take A Weight Loss Supplement?

There are a number of different ingredients that appear to be at least moderately effective weight loss agents, however, research suggests that taking any one single ingredient may not be the best approach. 

Instead, the best strategy may be one that combines a hypocaloric diet and regular exercise with multiple agents that cumulatively help to suppress appetite, increase lipolysis, and hinder the accumulation of fat.  

However, in order to see the best results from a weight loss product containing multiple ingredients, you have to do your research.  Make sure that you’re only taking clinically proven ingredients and that you’re taking them at appropriate dosages.  Furthermore, avoid products that have not been third party tested or customer-reviewed.  

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