Dietary Supplements and Bioavailability: Looking for Some Action?

Imagine a shopper in the supplements aisle debating buying brand A over brand B. Brand A says, “More bioavailable!” Brand B does not. To most consumers, the choice seems obvious. But is it really?


Thanks to the supplements industry, more consumers are familiar with the term bioavailability. The concept seems relatively simple. If ingredients aren’t absorbed and delivered in their proper form to the target site in the body (i.e., bioavailable), they can’t do their job.

“Something that is not bioavailable is useless,” says George Burdock, PhD, president and founder of Burdock Group (Orlando, FL). “It must be absorbed and in a form that is usable and gets to the target-whether it is applied to the skin, taken internally, or inhaled.” Exceptions do exist, he notes. An insoluble fiber that’s meant to pass through the body unabsorbed would still be considered bioavailable for its intended use.

For a majority of nutrients, however, efficacy depends in part on bioavailability, starting with absorption. A fine line can distinguish whether or not an ingredient is truly bioavailable. Chromium, for instance, is best absorbed as Cr+6 but is utilized in cells as Cr+3.

Moreover, absorption and bioavailability represent only part of the picture of whether or not a product will effectively address a health condition. To determine whether a supplement truly “works,” you must examine its actual mechanisms of action in the body.

Does It Work Better?
“If you were to ask people what bioavailability really means, I think many don’t really know,” says Loren Israelsen, executive director of the United Natural Products Alliance (Salt Lake City, UT). “In our industry, a lot of time and money is spent encouraging people to take brand A over brand B. Very seldomly, though, does there seem to be a clear understanding among consumers about why a product is better or different than another.”

“I think most consumers would assume that improved bioavailability means a product works better,” says Duffy MacKay, ND, vice president of scientific and regulatory affairs, Council for Responsible Nutrition (Washington, DC).

Federico Franceschi, PhD, a senior scientist at Indena S.p.A. (Milan, Italy), agrees that many consumers automatically translate “improved bioavailability” to mean “improved efficacy,” whether or not that’s been clinically proven.

Going on bioavailability claims alone, consumers may shell out more money for a product they believe works better. Franceschi says that in a U.S. market study Indena conducted several years ago, respondents indicated a strong interest in supplements proven to be more bioavailable. Moreover, they indicated they would be willing to pay more for such products.

After all, at the end of the day, all that matters to a consumer is how well a supplement is going to improve their wellness. “The consumer doesn’t give a flying hoot if more of a supplement got into the blood,” says Anthony Almada, president and CEO of GENr8. “They just want to know if a product works better for their health.”

As supplement marketers saturate the market with bioavailability claims, bioavailability has become somewhat of a catchword.

“Bioavailability is being used as a very cheap, indirect tool to [infer] that a product is better,” Almada says.

This is where industry-wide standardization could help, says MacKay. “We don’t really have any agreed-upon measurements for making these claims. I think there could be some voluntary guidelines put forth by industry, especially related to advertising claims, stating that if you want to say that something is bioavailable, what minimum evidence would be required.”

Beware the Competition
The need for a company to separate itself from questionable absorption and bioavailability claims is one that Albion Human Nutrition (Clearfield, UT) knows well. The company has specialized in high-quality mineral amino acid chelates for more than 50 years. Like bioavailability, the word chelate is being employed more often.

In chelate form, a mineral is absorbed by the body at a higher rate. Unreacted, a mineral is an inorganic element the body can’t process. To convert into chelates, which are organic forms the body can absorb and use, when minerals enter the body, they chemically bond with organic molecules, or ligands. However, several things can inhibit or disrupt the body’s natural process of forming a chelate, says Max Motyka, MS, RPh, Albion’s director of sales and marketing.

“Inorganic minerals need to be ionized before absorption. After an inorganic mineral ionizes, it is absorbed when it binds to a special carrier at the mucosal wall of the start of the small intestine. However, these charged minerals can have their absorption interfered with by reacting with other things encountered in the gut, such as fibers, phytates, oxalates, and certain fats or lipids. When they react with these items, an unabsorbable compound is formed and passed out through the colon.”

“In addition,” he adds, “these charged minerals compete with one another for the various carriers. Certain ionized minerals compete for the same carrier and thus block the absorption of one another (zinc blocks copper absorption, and calcium can hinder zinc absorption).” Finally, conditions such as Crohn’s disease, some duodenal ulcers, and irritable bowel syndrome can also interfere with chelate formation. By providing minerals as chelates that have already been reacted, it’s added assurance that a mineral will be efficiently absorbed.

Chelates can vary in quality, however. The choice of organic material, or ligand, that a manufacturer uses to bond with the inorganic mineral atom can affect how absorbable a chelate will be. For instance, if a ligand comprises large molecules, the resulting size of the chelate molecule will be larger and typically more difficult for the body to absorb. In general, the smaller the molecule, the greater the absorption rate. Albion uses amino acids-specifically glycine-to form its chelates, which the company says is superior not only for its small molecular size but also because it is nutritionally functional.

Manufacturing processes can also dictate chelate quality. Albion’s mineral chelates are spray dried, which the company says enables a complete reaction of all of the mineral into chelate form.

Despite the dense evidence a company like Albion has to show that its mineral chelates are fully reacted and absorbable-including more than 170 peer-reviewed published studies on its products-other companies may “borrow” science or even sell mineral chelates claimed to be true chelates but that are really only partially reacted or not reacted at all, says Motyka. “There are companies that are claiming to make chelates that are just like Albion’s, and they aren’t even chelates-just blended inorganic minerals with either hydrolyzed protein or some amino acids-blended, but not reacted to form the true chelate molecule,” says Motyka.

Unfortunately, consumers may not know the difference. “Consumers, with few exceptions, are not aware of the abuse of the designation of the terms chelate or amino acid chelate. They assume that all are the same. This is a very difficult conundrum to try and solve,” says Motyka.

With companies increasingly scrutinizing the competition, brands should be wary of making bioavailability claims unless they are certain they are sound. Take the example of a case handled last spring by the National Advertising Division of the Council of Better Business Bureaus. The case involved Nature Made’s Prenatal Multi+DHA Liquid Softgel Vitamins, a supplement said to provide a range of prenatal nutrients.

Competing manufacturer Perrigo Co. brought an advertising challenge against Nature Made, claiming that the Nature Made supplement did not adhere to the U.S. Pharmacopeia’s (USP) dissolution standards because the oil-based docosahexaenoic acid (DHA) omega-3 fatty acid in the product prevented the water-soluble folic acid from properly dissolving-thus, inhibiting the formula’s full bioavailability. NAD ultimately recommended that Nature Made discontinue using its “easy absorption” claim on the product’s label until the company established the bioavailability of the folic acid in the product.

“In the past, companies would say, ‘There’s no reason we’d think the ingredients in our formula would interfere with each other,’” says MacKay. “Now, it’s going to take more than someone just saying that. People are going to want to see scientific evidence that’s the case.”

Testing Challenges
To support absorption and bioavailability claims, testing is crucial. However, as experts point out, designing tests can be complicated.

For instance, what’s the best way to test how much of a nutrient is absorbed by the body through supplementation if that nutrient already exists in the body naturally or is quickly converted into other molecules?

Vitamin C is one of those ingredients, says John Endres, ND, chief scientific officer for AIBMR Life Sciences Inc. (Puyallup, WA). “Ascorbic acid is oxidized into dihydroascorbic acid very quickly, so it can be difficult to determine whether you’ve increased the level of vitamin C in the body,” he says. If a product is a pure compound or an ingredient not naturally found in the body in significant quantities, it can be easier, he adds.

However, it’s not impossible to test for bioavailability and absorption. “Any one of several methods can tell you not only if the substance was absorbed, but the rate of absorption and percentage of absorption,” says Burdock. “The biggest hurdle is developing an appropriate and accurate assay for the substance-remember, it may be metabolized in the gastrointestinal tract or in the body, once absorbed, so the assay method is going to have to test for the right substance.”

Radioactive tagging is one method industry has employed. Radioactive atoms can be incorporated in a substance-for instance, by growing a plant in a radioactive atmosphere of carbon-14 CO2, Burdock explains. Once the supplement containing these radioactive atoms is administered, samples can be taken at various intervals to determine how much radioactive carbon is in the blood, the breath, or the urine, all of which would indicate that the substance was absorbed. Other samples can determine if the substance reaches the target organ, such as the muscle or liver. In vitro testing can be conducted to determine if a substance reaches a specific receptor.

However, these methods can be expensive and time consuming, Burdock says. “So people often just take the same kind of samples and measure some chemical marker for the administered substance.”

Determining where and when to test is also important, says MacKay: “It varies according to ingredient.”
For example, although eicosapentaenoic acid (EPA) and DHA omega-3 fatty acids from fish oil might show up in blood serum soon after supplementation, only over time do those nutrients begin accumulating in cell membranes of fatty tissues such as brain tissue, where cognitive benefits actually take place. “So, if you tested for omega-3 in the serum only, it might be an inaccurate way to test for long-term accumulation,” MacKay says.

How Much Is Too Much?
Improved bioavailability may be a good thing-but can an ingredient ever be too bioavailable? “More absorbability doesn’t always mean better use by the body,” says MacKay.

For one, the body may limit how much of a nutrient it can absorb. “For instance, the body tightly regulates calcium levels and can only absorb a limited amount of calcium at a given time. So, if you take a whole bunch of highly absorbable calcium, your blood levels may shoot up for a while, but your body can only put calcium into your bones so quickly. So then your kidneys will work overtime to excrete the extra calcium,” MacKay says. “If the level of an ingredient goes beyond a threshold, sometimes you’re just more active at excreting it as well.”

Too much bioavailability could also raise questions about toxicity and safety. “More might be better, but sometimes too much may not be great. When you start to say that an ingredient is 600 times more bioavailable, is that safe?” he asks. When hiking up absorbability and bioavailability to levels never seen before, depending on an ingredient’s history of safety, additional safety studies may be required.
Also, MacKay adds, “Consumers can’t assume that because an ingredient is 600 times more available that you can take one-sixth of the amount; it doesn’t always work that way.”

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