3 Supplement Combinations That Are Actually Synergistic

Supplement Synergy

The term “Synergy” is often misused in the context of dietary supplements, probably because the easiest way for greedy supplement companies to get away with under-dosing is to tell you (the consumer) that the ingredients in a particular supplement “synergistically enhance” the effects of each other.

Every supplement company acts like it has the magic formula that you’ve been looking for and no competitor even comes close to what they’re offering.  In reality, the supplement industry is so saturated these days that for every solid formula–whether it be a pre-workout, a protein supplement, or a fat-burner–there are a bunch of other pretty solid formulas that are extremely similar and just as effective.

So, it comes as no surprise that supplement companies rely heavily on marketing to sell their otherwise easily matched products.  Sure marketing is important, but there always comes a point where the lingo starts to become misleading.  One of the most misleading terms I’ve seen regularly while researching various supplements is the term “synergy”, but rarely is it justified.

While there are many ingredients which are hypothesized to act in synergy, only a handful of ingredient combinations have been studied to the point where we can actually conclude there is indeed synergy.

First, What Is Synergy?

If you look up the term “synergy” in the English Dictionary you’ll likely find something along the lines of:

“the interaction of elements that when combined produce a total effect that is greater than the sum of the individual elements”

Elaborating on this definition, we can conclude that two (or more) molecules are Synergistic when their combined effects are greater than the sum of each individual molecule on it’s own.

When it comes to supplements, there are three basic ways to describe the relationship between two or more ingredients:

  • Antagonistic – The ingredients make each other less effective
  • Additive – The ingredients produce effects which are equal to the sum of their individual effects
  • Synergistic – The ingredients products effects which are greater than the sum of their individual effects

If you like to think about things numerically, look at it like this…

  • Antagonistic is when 1 + 1 = < 2
  • Additive is when 1 + 1 = 2
  • Synergistic is when 1 + 1 = > 2

You see, it’s incorrect and incredibly misleading when companies refer to ingredients as “synergistic” when there isn’t any scientific evidence to support those claims, yet it’s become commonplace in the marketing of supplements.

Much of the time, when a supplement company claims the ingredients in their formulas are “synergistic” or one ingredient is “synergistically enhanced” by another, what they really mean are that two (or more) ingredients produce an additve effect.

For example, Beta-Alanine and Creatine both enhance exercise performance.  This is well documented by dozens of well-designed, placebo-controlled studies so there’s no denying these substances are effective.

However, the mechanisms by which they work are entirely different.  Research indicates that a combination of Creatine and Beta-Alanine produces the effects of both substances, but the magnitude of these effects are not greater than the magnitude of their individual effects.  In other words, Creatine and Beta-Alanine are additive, but not synergistic.

Now that we’ve established the difference between an additive effect and a synergistic one, let’s talk specifics.  Here are three examples of proven synergy between supplement ingredients…

Theanine + Caffeine

Theanine and Caffeine are both found in Green Tea where they have long been believed to interact with each other in a unique, possibly synergistic manner.

Since Green Tea is the only known plant in which both of these molecules are present in high enough doses to be biologically active, it makes sense that the notion that Caffeine and Theanine are perhaps synergistic came from the observation that Green Tea—despite containing Caffeine—is more of a relaxation drink than an energy drink.

Sure enough, several studies have been conducted to test the hypothesis that Theanine and Caffeine are synergistic and the results are quite encouraging.

Theanine has been shown to enhance the mental effects of Caffeine (alertness, focus, etc.) while reducing the negative side effects (jitters, anxiety, etc.) which commonly occur with Caffeine alone.

Several randomized, double-blind, placebo-controlled studies (the holy grail of study structures) have confirmed these findings so at this point it’s undeniable.  Theanine and Caffeine are indeed synergistic!

If you use Caffeine, for any reason, you should also use Theanine.  It increases the beneficial effects and reduces the negative effects.  There’s just no reason NOT to use them together…other than the fact that Caffeine is cheap and Theanine is a little on the expensive side.

That’s why most supplement companies either don’t use Theanine in their Caffeine-based products, or just don’t use enough.


Several different doses of Caffeine and Theanine have been used through various studies, in different ratios as  well.  It’s more about finding you’re ideal range of both ingredients, but a good place to start is atleast 50-100mg of Theanine and say, 100mg of Caffeine.  If you drink a lot of Caffeine, then you’ll need more Theanine.  Matching them appears to be a pretty reliable way to go.

Synephrine + Hesperidin + Naringin

Synephrine, Hesperidin, and Naringin are all naturally occurring molecules in certain Citrus fruits such as Bitter Orange.  Bitter Orange, while not commonly eaten (due to its bitter taste) is commonly processed into an extract and sold as a dietary supplement for weight-loss.

Needless to say, this has piqued the interest of researchers which has led to extensive research on Bitter Orange and its constituents, especially Synephrine.

Synephrine is a beta-receptor agonist, meaning it stimulates the receptors (beta-receptors) which induce Lipolysis (fat-breakdown).  This is the same basic mechanism as Ephedrine (now banned).

Naringin and Hesperidin are both flavonoids which have been studied individually and have each been shown to increase Adiponectin, a protein which is responsible for regulating glucose uptake and fatty acid breakdown.

Since these molecules are often found alongside each other naturally, it makes sense that researchers would want to investigate them together.

A combination of Synephrine (50mg), Naringin (600mg), and Hesperidin (100)mg has been shown to increase Resting Metabolic Rate by approximately 180 calories, compared to placebo.

Interestingly, the same study that observed these results tested varying doses of Hesperidin and found that 1000mg of Hesperidin was actually worse than 100mg.

Further research indicates that this combination is well-tolerated, even over a 60 day period of consistent use, so there’s no reason to consider Syneprhine–or it’s combination with Naringin and Hesperidin–dangerous.

So, not only are Synephrine, Naringin, and Hesperidin synergistic in that they enhance the total RMR increase induced by Syneprhine, but the ratio matters.  Usually, we assume more is better, but this is one of those rare situations where less is more.


Combine these ingredients or find a supplement which contains these ingredients in the following doses:

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

It is possible that, upon further study, researchers will find an even more ideal combination, but for now this is the precise combination that will produce the largest increase in RMR and ultimately induce weight-loss the quickest.

Curcumin + Piperine

Curcumin is the chief molecule belonging to the group of molecules known as Curcuminoids, commonly extracted from plants like Turmeric (a relative of Ginger).

Curcumin itself possesses potent anti-inflammatory properties which s why it appears in many joint support formulas and is commonly used as a treatment for Osteoarthritis.

Unfortunately, Curcumin by itself has a relatively low bioavailability, meaning even doses of 10 grams (yes grams) and up (not realistic via supplementation) would be needed.  This also means that any joint support supplement that only contains Curcumin by itself, with no way of enhancing absorption, doesn’t really work well.

Fortunately, Piperine, a molecule found in Black Pepper which has long been thought to increase the absorption of other compounds, has been studied in conjunction with Curcumin.

Research has confirmed that Piperine (from Black Pepper) can increase the bioavailability of Curcumin by up to 2000%.  That’s not a typo.  We’re talking about the difference between something that flat out doesn’t work and something that is actually quite effective, just because of a little Piperine.  That’s synergy!

If you’re using Curcumin for anything, especially joint support, you should be pairing it with Piperine to make sure you’re actually gettin something out of it.


Curcumin is usually dosed around 100-500mg, depending on what it’s being used for.  Piperine is dosed around 5-10mg.  It’s pretty simple.

The Bottom Line On Supplement Synergy

It’s a shame that so many supplement companies use the term “synergy” when they really mean additve.  In fact, it’s downright unethical if you ask me.  True synergy is rare, but can make all the difference when it comes to product formulation.  There are naturally occuring synergies between molecules and taking advantage of these synergies is important when it comes to maximizing the benefits that can be obtained from any given supplement.

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