Functional Solutions For Dietary Supplements

Tuesday, September 12th, 2017

Many plant extracts have components that are believed to offer health benefits, but not all are readily absorbed into the human bloodstream. Cyclodextrins can increase the bioavailability of these health-promoting ingredients. By Dr TiehKoun Koh, business director food solutions, and Dr Zhang Yan, head of food lab, Wacker Biosolutions.

Rising affluence, changing demographics and growing health awareness among consumers are increasing the demand for food products and ingredients that can do more than just satisfy hunger. Consumers, both globally and in Asia, are more frequently opting for dietary supplements or food products with additional benefits—so-called ‘functional foods’—to enhance their wellbeing.

Functional foods are experiencing a strong increase in popularity, as scientists and food researchers are continuously discovering new health-promoting ingredients that make the body resistant to environmental stress, prevent certain diseases, or even slow the ageing process. Consequently, the market for functional foods is currently growing and further expansion is expected.

According to a market study by Mordor Intelligence, the global nutraceutical market (comprising the functional foods and beverages market and the dietary supplements market) is expected to reach around US$385 billion by 2020, growing at a compound annual growth rate of 7.5 percent from 2016 to 2021.

While the US is clearly leading the field, the Asia-Pacific region is following closely, and is expected to become the second biggest market for functional foods by 2020.

Yet, health-promoting ingredients such as vitamins can be demanding in terms of formulation as many functional ingredients are not water-soluble. It is therefore very challenging to formulate a functional food or dietary supplement with hydrophobic (water-hating, i.e. non watersoluble) active ingredients and, at the same time, ensure adequate bioavailability for the consumer.

A possible solution lies in cyclodextrin technology, which can encapsulate hydrophobic actives and enhance their bioavailability.

Cyclodextrin Technology

Cyclodextrin Technology

Cyclodextrins are ring-shaped sugar molecules (oligosaccharides) that have been known to science and research for over 100 years. According to the number of glucose units, a distinction is made between α-, β- and γ-cyclodextrin: α-cyclodextrin consists of six, β-cyclodextrin of seven and γ-cyclodextrin of eight glucose units.

As natural starch conversion products, cyclodextrins can be biotechnologically produced for industrial use by enzymatic degradation from starch-containing raw materials, such as corn or potatoes. They are non-allergenic, vegetarian and are produced from renewable raw materials.

Cyclodextrin molecules’ special feature is their ringshaped, three-dimensional structure. It creates an interior hydrophobic cavity which is able to accommodate a lipophilic molecule as ‘guest’, provided that its size and shape are compatible. The hydrophilic (water loving, i.e. water-soluble) exterior, on the other hand, ensures compatibility in aqueous systems.

In the presence of water, the cyclodextrin-encapsulated functional ingredients form ‘molecular dispersions’, resulting in enhanced bioavailability of hydrophobic substances.

Enhanced Bioavailability Of Curcumin

A good example is complexing curcumin with cyclodextrin. Curcumin is the major colouring matter and the biologically active constituent of the herb curcuma longa, also known as turmeric. Curcumin not only lends food a beautiful yellow colour; it has also been a part of traditional remedies for centuries, especially in Indian and Chinese medicine.

Today, modern science has proven its positive effects, too, and current clinical trials make curcumin one of the best investigated natural compounds to date. The main mode of action is via free-radical scavenging, as curcumin is a powerful antioxidant.

It has been shown to demonstrate remarkably antiinflammatory, anti-arthritic, as well as hypoallergenic, antibacterial, and even anti-carcinogenic effects. But, curcumin is quite poorly absorbed by the human body, and for this reason, its use in nutritional supplements has often been limited.

Curcumin exhibits highly hydrophobic properties, which explains why it is barely absorbed into the bloodstream. Pure curcumin extract agglomerates in the human body; only a few curcumin molecules from the small surface area of the agglomerates are absorbed, and the remaining bigger portion is generally excreted without uptake.

Conversely, there is far greater absorption of hydrophilic compounds. This is where γ-cyclodextrin comes into play. As mentioned, the inner surface of cyclodextrins is hydrophobic, whereas the outer surface is hydrophilic. The fat-soluble curcumin slips into the core of the γ-cyclodextrin. The latter’s hydrophilic surface boosts the bioavailability and thus the solubility of curcumin within the human body.

Taken as a dietary supplement, mostly in the form of a capsule, the curcumin-cyclodextrin-complex is transported unchanged through the stomach into the upper intestinal tract. There, only the curcumin molecules are absorbed into the body from the epithelial cell membrane.

The oligosaccharide γ-cyclodextrin is hydrolysed by human pancreatic amylase, yielding mainly maltose, some maltotriose and smaller amounts of glucose. Maltose and maltotriose are degraded to glucose, which is then being absorbed from the small intestine into the blood.

As a result, about 40 times more curcumin is absorbed directly into the blood vessels, compared to pure curcumin powder and some leading commercial curcumin supplement products.

Scientific Evidence

Several scientific studies were conducted to prove the positive effect of complexing curcumin with γ-cyclodextrin. In a human clinical trial, for example, researchers compared the relative absorption of the curcumin-cyclodextrin-complex with pure curcumin extract (95 percent) and two commercially available curcumin preparations designed to increase bioavailability.

In the trial set-up, 12 individuals (fasted overnight) were given the four different curcumin preparations orally—with a one-week washout period in between the four formulations. After product intake, blood was drawn hourly for 12 hours and analysed (spiked plasma samples), and the blood concentration of curcumin and its derivatives was determined.

The AUC (area under the curve) plasma concentration and relative absorption clearly displayed that the complexed formulation was absorbed up to 40 times more efficiently than the standard extract, and at least 4.5 times better than the next best comparable commercial product.

These results underline the significant increase in bioavailability of curcumin in a cyclodextrin-based formulation. Furthermore, these data suggest that the curcumin-cyclodextrin-complex can provide the benefits of the powerful antioxidant curcumin to a much greater extent than existing commercial products.

Highly Bioavailable Coenzyme Q10

Another interesting functional ingredient is Coenzyme Q10 (CoQ10), also known as ‘ubiquinone’. This fat-soluble, vitaminlike substance can be found in almost all living cells, as it plays a central role in human cells in generating energy for the body.

CoQ10 is well known as a redox carrier in the mammalian respiratory transport chain and acclaimed as an antioxidant for free-radical scavenging. Numerous studies also indicate a role for it in cardiovascular health. However, ageing, stress, certain medication, strenuous exercise and other lifestyle-related factors may reduce the levels of CoQ10 in the body.

As its concentration in a person’s body further decreases with age, dietary supplements are a proven way of keeping the stores of CoQ10 well stocked. The down side: coenzyme Q10 has very poor water solubility and thus very little bioavailability.

Again, the absorption of CoQ10 can be enhanced considerably via molecular inclusion in γ-cyclodextrin. After being stirred into liquid, the coenzyme tucked into the cyclodextrin forms a molecular dispersion which the body can absorb much more readily. In vitro and in vivo studies have shown that coenzyme Q10 uptake can be substantially improved by complexing with γ-cyclodextrin.

A two-step in vitro assay was performed to investigate, first, the micellerisation efficiency and, second, the uptake efficiency in human CaCo-2 cells (gut cells).

The cyclodextrin-CoQ10-complex was up to three times more efficiently micellarised when compared to commercial CoQ10 supplements or the CoQ10 powder itself. The following uptake-efficiency study with human CaCo-2 cells also demonstrated an eight times higher uptake of the encapsulated CoQ10.

In a further in vivo study, CoQ10-plasma concentrations of 22 healthy individuals were recorded after oral administration of one dose of the cyclodextrin-CoQ10-complex. The patients receiving the cyclodextrin-based formulation showed 18- fold higher bioavailability (as measured by the AUC plasma concentration of CoQ10) when compared to a control dose of a physical mixture of microcrystalline cellulose (MCC) and CoQ10.

For A Variety Of Applications

For versatile food and beverage applications, cyclodextrins have remarkable properties to offer. Biotechnologically produced from renewable, vegetable raw materials, cyclodextrins are fully in line with the trend toward avoiding animal-based raw materials, especially as consumers increasingly demand naturally manufactured products or products with ingredients from renewable sources.

By complexing challenging ingredients such as curcumin or coenzyme Q10 with cyclodextrins, the solubility of these oleophilic substances, and thereby their bioavailability, can be improved significantly.

Cyclodextrin-based formulations further come as a dry, free flowing powder, which makes them especially suited for use in dry or powdery dietary supplement products, such as tablets, capsules and nutritional bars. Since the powder disperses easily in aqueous systems, it is also available for use in beverages.

This makes cyclodextrin formulations an ideal solution for food and beverage applications to enhance the bioavailability of otherwise poorly absorbed substances.