Synephrine: A Safe, Effective Weight-Loss Supplement


Synephrine is a molecule that is naturally occurring in certain plants as Bitter Orange, but is also produced endogenously in the human body via oxidation of Octopamine.

Chemical Structure

Synephrine is often described as “a less effective (but safe) form of Ephedrine” but that’s an oversimplification.  In terms of chemical structure, the two compounds are quite different so it’s not accurate to compare them like that.

Ephedrine Vs. Synephrine

Again, you don’t need to sit there and analyze the differences in chemical structure (unless you want to), but just take note of the fact that, while there are some similarities between Synephrine and Ephedrine, they are completely separate compounds.

How Does Synephrine Work?

Synephrine is a beta-adrenergic receptor agonist, meaning it can directly stimulate lipolysis, the breakdown of fat.

In this regard, it is quite similar to Ephedrine.

They share the exact same mechanism of action, but Synephrine is weaker (and also safer).

By increasing Lipolysis, it is able to increase the Metabolic Rate which, overtime, can lead to meaningful weight-loss.  But let’s discuss this whole Metabolic Rate thing first…

What Does The Research Say About Synephrine?

The term “Metabolic Rate” simply refers to the amount of calories you burn at rest in a given time period.  Think calories per day.  There are many factors that contribute to your Metabolic Rate (calorie consumption, level of physical activity, the temperature, etc.) but it is entirely possible to increase it through supplementation.

One of the issues with the research on Synephrine has been that some studies use it in combination with other molecules, making it difficult to gauge the effects of Synephrine alone.

Well, in a double-blind, randomized, placebo-controlled study which was published in the International Journal Of Medical Sciences, researchers pitted Synephrine by itself against several combinations of Synephrine and Citrus bioflavonoids (naturally occuring with Synephrine in Bitter Orange) Naringin and Hesperidin.

There was one placebo group and four treatment groups

  • Group 1:  Placebo (V8 Juice Only)
  • Group 2: V8 Juice containing – 50mg Synephrine
  • Group 3: V8 Juice containing – 50mg Synephrine + 600mg Naringin
  • Group 4: V8 Juice containing – 50mg Synephrine + 600mg Naringin + 100mg Hesperidin
  • Group 5: V8 Juice containing –  50mg Synephrine + 600mg Naringin +1000mg Hesperidin

The results are depicted in the following chart:


Note that the reason the Placebo group experienced a negative Metabolic Rate increase (a decrease) is because the V8 Juice used contained calories.  Therefore, when evaluating the effects of the control groups, we need to adjust accordingly.

Using the Placebo Group as baseline, these were the Metabolic Rate increases for each protocol:

  • Control 1: 65 calorie increase
  • Control 2: 129 calorie incerase
  • Control 3: 183 calorie increase
  • Control 4: 79 calorie increase

Perhaps the most intriguing aspect of these results is that Control Group 4, the group that took the most Hesperidin, experienced less of an increase than both Control Groups 2 and 3, meaning more Hesperidin isn’t better.

The most effective of the treatments was

  • 50mg Synephrine
  • 600mg Naringin
  • 100mg Hesperidin

The most notable increase in Metabolic Rate seen was 183 calories above placebo.  This may seem like a trivial amount at first, but what if, by simply taking these ingredients, you burned an additional 183 calories per day.  That’s 1261 calories a week that you burned without doing anything.

Given that you need to burn about 3500 calories to lose a pound of fat, you’d be losing about 1 pound every 3 weeks, again, without doing anything.  That matters!

Further Research On Synephrine

A recent 2016 study, published in the British Journal Of Clinical Pharmacology, found that Synephrine supplementation prior to exercise decreased carbohydrate oxidation while increasing fat oxidation, and increased maximum fat-oxidation.

Synephrine Increases Fat Oxidation

The following set of graphs depicts the effects of Synephrine supplemtation on total energy expenditure, heart rate, and fat oxidation relative to carbohydrate oxidation during exercise.

As you can see, total energy expenditure stayed the same in both groups, as did heart rate, but Synephrine supplementation caused more fat burn and less carb burn.  It’s also worth noting that Synephrine supplementation increase maximum fat-oxidation compared to the placebo.

What does this all mean?  It means Synephrine causes your body to burn more fat during exercise and is well tolerated at pretty high dose (3mg/kg).

Is Synephrine Legal?

In the United States, Synephrine is entirely legal, but it’s certainly been a topic of discussion for the FDA.

Multiple warnings letters have been sent to companies that use Methylsynephrine, an alternate form of Synephrine that the FDA claims doesn’t fit the guidelines for a dietary supplement ingredient and is therefore mislabeled when sold as such.

Concerns about products contain Bitter Orange Extract stem mostly from the fact that they can easily be adulterated, but studies have shown that non-adulterated Bitter Orange Extract and Pure Synephrine are safe.  Even the FDA had to finally admit that.

Unfortunately, Synephrine has drawn concerns from officials in other countries including:

It’s worth mentioning, however, that Health Canada recently relaxed the rules on Synephrine by now classifying 50mg/day as a Type 3 Health Risk, meaning it’s not likely to cause adverse effects.  This is the wake up scientific research which indicates, pretty clearly, that Synephrine is not dangerous.

This is good news for the millions of people who already use Synephrine as a safe, effective weight-loss supplement and are concerned about regulations taking that away from them.  There have certainly been plenty of legal disputes around it, but the science is quite clear.  Synephrine is safe and therefore should remain legal.

If you’re living in Canada, it’s actaully quite convenient that you’re permitted to take up to 50mg/day which just so happens to be a clinical dose.  That’s all you need anyway!

Does Synephrine Have Any Side Effects?

Despite what many critics say about Synephrine being related to Ephedrine and therefore dangerous, research has actually proven it to be remarkably safe.  Supplementation, even at high doses like 50mg at once, produces no noticeable changes in blood pressure and has not been shown

A recent review, published in the International Journal Of Medical Sciences, concluded that:

“p-synephrine alone or in combination with caffeine does not appear to produce significant adverse cardiovascular effects or pose a risk to human health at doses commonly ingested orally”

The researchers went on to say that no adverse effects have been directly tied to Synephrine, even in combination with other stimulants.

“The data accumulated to date do not support hypothesized concerns regarding potential adverse effects of p-synephrine”

It’s also worth noting that, in the study discussed above from the British Journal Of Clinical Pharmacology, a higher than average dose (3mg/kg) was well tolerated and had virtually no influence on heart rate.  This makes it a much safer alternative than other stimulants that are commonly used as fat-burners (such as Ephedrine).

Stacking Synephrine For Better Results

Synephrine by itself causes subtle increases in the amount of fat you burn.  It’s not miracle weight-loss supplement, but it is effective when used correctly.  Stacking it with other ingredients such as Caffeine, Naringin, and Hesperidin will amplify the effects so ideally, you should look for a supplement that contains all these at doses of:

  • Synephrine: 50mg
  • Caffeine: 100-300mg (depending on personal tolerance)
  • Naringine: 600mg
  • Hesperidin: 100mg

It’s important that this precise ratio remain intact, as research indicates more Hesperidin (1000mg) is actually less effective than 100mg.  A rare instance of “more isn’t always better”.  Definitely something to pay attention to…

Another effective way of stacking Synephrine is pairing it with an alpha-receptor antagoist, such as Rauwoslcine, which essetially functions as the inverse of Synephrine and may indeed be quite synergistic.

One stimulates Lipolysis (Synephrine) while one stops Lipolysis from stopping (Rauwolscine).  Together, these two supplements are extremely effective for inducing fat-loss in a relatively short period of time.

Rauwolscine Synephrine


Again, Synephrine by itself is not miracle but it can contribute meaningfully to your fat-loss regmien and is entirely safe.  When combined with the right additional supplements (like the one’s above) and used in a conjunction with a responsible diet and exercise program, Synephrine is a worthwhile tool to have in your fat-loss arsenal.

The Bottom Line On Synephrine

Syneprhine is a safe, effective supplement for burning fat and losing weight.  Although is has been compared to Ephedrine by some, it’s actually proven to be quite safe, even at doses of 50mg/day.

Stacking Synephrine with complementary supplements (such as Naringin, Hesperidin, Rauwolscine, etc.) is a great way to amplify the effects as well.

If fat-loss is the goal, you should be supplementing with Synephrine. exists to educate the supplement community and seperate the science from the hype.

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