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Supplements That Don’t Work as You Intended (But May for Other Reasons)
Kurtis Frank

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Go to any drug store, and you will likely find an aisle full of supplements, all promising a healthier you. You've probably seen ads and doctors telling you how secret supplement X is all you need to unlock your potential. Is there any truth to these grandiose claims? We decided to look at some, but with a twist--instead of just saying what works or doesn't, we wanted to cover supplements that do work, but not for the reasons you usually see.

Chrysin


Chrysin is a flavonoid molecule commonly found in propolis (a bee product), that upon incubation with testicular cells causes dose-dependent increases in testosterone synthesis. Based on this evidence, as well as its low cost, it was introduced into a variety of testosterone-boosting supplements.

Despite a fair bit of evidence of testosterone in chrysin, there is not much to support the testosterone-boosting claim. This seems to be related to its bioavailability -- i.e., the percentage of the drug that you ingest that actually appears in the blood. Chrysin’s bioavailability is usually less than 1 percent.

This poor absorption results in most chrysin being shuttled to the colon and then excreted in the feces. This may be the one area of the body where chrysin has benefit, however, as it appears to confer anticarcinogenic effects in colonic cancer cells and intestinal cells. Granted, the effect is small, but it is present.

Bottom line: Touted to boost testosterone, chrysin fails to do so due to poor absorption. However, it may be a colon health supplement with anti-cancer effects.

Tribulus

Tribulus is a rare supplement. Usually when it’s said that a supplement doesn’t boost testosterone, it is based on a lack of evidence to support an increase in testosterone--i.e. the studies have not been conducted. While absence of evidence is not evidence of absence, conclusions cannot be drawn when the evidence just doesn’t exist.

Tribulus, however, actually has evidence demonstrating that commonly supplemented doses do not increase testosterone in any species. It appears to remain on the market as a testosterone-booster in part due to its notoriety and in part due to its purported libido-enhancing effects (which remain largely unsupported by research). Many people confuse an increase in libido to be equivalent to an increase in testosterone, but that is not the case.

As a side note, tribulus is one of two berries called “gokshura,” with the other being the plant Pedalium murex. The latter actually has at least one rat study to support increases in testosterone, so it is possible that early researchers investigating the benefits of “gokshura” simply got the wrong herb.

Is tribulus worthless? Not completely. Although the evidence is not the best at this moment, both traditional claims and preliminary animal evidence support the usage of tribulus for urogenital health (reducing kidney stone formation, increasing urinary flow rate, possibly antibacterial like cranberries, etc.) The animal evidence also supports the aphrodisiac effects of tribulus--at least one study shows its effects as comparable to Viagra (although Viagra is more pro-erectile than libido-enhancing), and these effects occur at reasonable doses of tribulus.

Bottom line: Despite there being ample evidence to disprove a testosterone-boosting effect, tribulus may still have a role in enhancing libido and perhaps urogenital health.

Conjugated Linoleic Acid


Conjugated Linoleic Acid (CLA) is one of a few supplements to hold the dubious prestige of being a fat-burning compound that has also been associated with increasing fat gain. This may be wishful thinking, but fat burning compounds shouldn’t make you fat.

To be fair, the vast majority of the evidence is torn between “a small positive effect” and absolutely no effect. It isn’t really known what CLA does in the body or how; all we know is that for the purpose of fat loss, the effects of CLA are highly unreliable.

Ever seen a study with an average value and range of 1.00+/-5.12 pounds lost? CLA routinely has such a wide variability that despite the average being “positive,” some participants appear to have gained weight. This lack of reliability prevents CLA from being known as a good fat burner, but the fact that positive studies can be cherry-picked from the evidence is enough to prolong the life of CLA in the supplement industry.

Bottom line: A boring molecule that has no benefits beyond its potential to burn fat, due to the variability of results, it can be dubiously regarded as both a fat-burner and fat-gainer and due to this, it is inadvisable to be using CLA as a fat burning supplement

Evodia Rutaecarpa


Evodia is an interesting berry from traditional Chinese medicine. It came to fame as it was one of two traditionally known “warming” medicines; the other being Ephedra sinicus (the source of ephedrine, a proven fat burner). Due to the traditional usage, evodia was commonly put into supplements, and even now you can find supplements with the compounds evodiamine or rutaecarpine in them, which are the bioactives in evodia.

Funny story: evodia literally makes you feel warmer independent of changes in metabolic rate (perhaps secondary to reducing the ability of the body to perceive cold, also seen with hot pepper extract). This is due to activating a receptor known as TRPV1, a vanilloid receptor on neurons, and is possibly a reason why the molecules are still included in fat burners and won’t be purged from the fat-burning section of the supplement store. If it feels like you’re burning fat, you must be!

Studies looking into the true fat-burning effects of this herb are unspectacular, use high doses of evodiamine in isolation, and do not suggest much promise with the fruit.

Perhaps ironically (as they both are “fat-burning” compounds in supplements), the bioactive compound known as rutaecarpine is able to potently reduce the amount of circulating caffeine in the blood when the two are coingested. This is due to increasing the activity of the enzymes that degrade caffeine, and 80mg/kg of rutaecarpine (a decently high dose) can reduce the overall exposure of caffeine to 5 percent of what it would normally be without rutaecarpine.

Bottom line: Feeling warmer from evodia fruits may be just that, rather than a side effect of an increased metabolic rate. While there is no evidence to support the usage of evodia or its bioactives as a fat burner, sometimes feeling warmer is nice.

Evodia fruits may have a role in reducing the effects of caffeine via increasing the rate of its metabolism.

Policosanol

If conspiracy theories are your thing, then policosanol is a supplement that would be worth looking into. Policosanol is a term used to refer to lipids derived from cane sugar which supposedly have a role in reducing cholesterol. Due to notoriety gained from the research coming out a few decades ago, they have been and remain fairly popular and common.

At the time when research was most prevalent (70-80s), it appears that policosanols were touted to work only if derived from authentic Cuban cane sugar. This claim has since been disproven--Cuban cane sugar is identical to cane sugar grown in other countries.

Looking at the research, there appears to be 16 studies conducted in Havana, Cuba, all of which show that policosanol has potency similar to statin drugs for reducing cholesterol. When looking at studies excluding data from Cuba, two studies suggest weak cholesterol-reducing effects, while 12 show absolutely no benefit. The studies conducted outside of Cuba and those conducted afterwards in other countries, for the most part, have exactly the same dosing and dietary regimens, and the studies conducted outside of Cuba are published independently of pharmaceutical companies (who might have a conflict of interest with statin drugs and profit thereon).

Building off of that, cane sugar was a major export from Cuba at that time.

The probability of the huge difference in results based on location not being related to some external influence (as methodology and sourcing of products are similar) is next to nothing; some external (possibly financial) influences are much more probable.

Bottom line: The cholesterol-reducing effects of policosanol have a very high chance of literally being lies, and more reliable evidence suggests absolutely no effect rather than statin-like effects. There are possible anti-diabetic effects that seem more promising and reliable, but these require more research.

Glutamine


Glutamine is a conditionally essential amino acid that is commonly ingested as a bodybuilding supplement due to the following reasons:

• glutamine is present in very high levels in skeletal muscle;
• it augments muscle protein synthesis by leucine;
• it causes dose-dependent increases in muscle size when incubated in a muscle cell

The in vitro (in cells outside of a living system) data is astounding, but unfortunately it does not carry over to living models. Glutamine serves not only to regulate muscle protein synthesis but also to shuttle nitrogen around the body (alongside other small amino acids, such as alanine), and appears to be tightly regulated by the body. Orally ingested glutamine does not appear to cause spikes of glutamine in the muscle, and since the glutamine is not there, it cannot act on the muscle.

This is mostly due to the intestinal wall and the liver sequestering the glutamine supply, as intestinal cells divide rapidly enough to use glutamine as a source of energy, similar to how muscle cells would use carbohydrates or fatty acids, and the liver takes a large share in first-pass metabolism.

The promise that glutamine currently holds is for prolonged aerobic exercise (jogs or bicycle rides exceeding two hours or so), as glutamine levels in the blood naturally fall during such activity, and replenishing glutamine appears to preserve performance. There is also a role of glutamine in intestinal health, where provision of glutamine aids the integrity of intestinal cells and can improve the functioning of the intestines.

The role of glutamine in suppressing carbohydrate cravings (which is a surprisingly common anecdote) has not been investigated yet, but is plausible. Carbohydrate cravings (in preference of fatty acids) are associated with serotonin, and these receptors are present in the intestines to a high level.

Bottom line: rather than being a muscle-building agent, glutamine appears to be something to give to endurance athletes or persons with intestinal disorders.

Horny Goat Weed

Horny goat weed (HGW) is the common name for the herb genera known as Epimedium. This herb gets its common name due to the discovery that goats that eat it become quite horny.

It is marketed for three main purposes: testosterone boosting, libido enhancement, and improved erectile function. For testosterone boosting, there is some limited evidence that the main bioactive of HGW (Icariin) can increase testosterone in rats, but only at an incredibly high oral dose of the supplement; definitely not practical for supplemental purposes (and even then, no human evidence exists). Although a testosterone-boosting effect cannot be ruled out, it seems unlikely.

The libido aspect is surprisingly based mostly off of anecdotes, without too much investigation into the subject matter. It seems to increase libido, but not remarkably when compared to other libido-enhancing herbs.

Similar to the above two claims, limited evidence exists to support the usage of HGW as a pro-erectile. Interestingly, these mechanisms appear to be secondary to improving blood flow and thus preventing the anti-erectile effects of poor circulation.

Therein lies the benefit with epimedium. Even in traditional Chinese medicine, this herb is touted to aid cardiovascular health, which is partly due to interactions with nitric oxide metabolism and partly due to estrogenic effects (although not large enough to be of concern to males, and in fact may be cardioprotective). Secondary to the estrogen-mimicking effects, epimedium is also potentially useful for preventing menopausal bone loss. Although limited human evidence exists, there is a seemingly large amount of rat data in support of this.

Bottom line: There may be a role for increasing erections with horny goat weed, but the testosterone-boosting effects seem unlikely. Despite this, the herb may be cardioprotective and useful in menopause.


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