Enhancing Bioavailability of Supplements Through Nanotechnology

Alt Text: A representational image of supplement capsules developed through nanotechnology

Have you ever wondered why certain nutritional supplements should be taken with food or on an empty stomach? Understanding the optimal timing for taking nutritional supplements can significantly influence the absorption and bioavailability of active nutrients. Bioavailability refers to the extent at which a nutrient becomes entirely available for its intended biological site(s) of action. This article provides a comprehensive explanation on the bioavailability of supplements, examines factors that hinder nutrient absorption and solubility, and explores how advancements in nanotechnology overcome these challenges to maximize therapeutic potential. Use the links below to jump ahead to different topics on the page.

Bioavailability — An Integral Component of Pharmacokinetics

Pharmacokinetics is the movement of nutrients and drugs through the body. There are four components of pharmacokinetics, the ABCD’s, and these processes help determine the ideal dosing and timing to achieve optimal therapeutic effects. 

• Administration refers to the route and dosing of the nutrients.  

• Bioavailability is the unaltered fraction of the nutrient’s active form that reaches systemic circulation.

• Clearance is the active form of a nutrient or drug being removed from systemic circulation.  

• Distribution measures how widely a nutrient or drug can travel to fluid compartments of the body.  

Bioavailability defines the extent to which a nutrient interacts with an individual’s physiology,  ultimately determining the success or failure of a supplement’s efficacy. Hence, supplements are formulated to optimize the absorption and solubility of their nutrients. 

High bioavailability of a nutrient translates to a more powerful and more immediate physiological response. In contrast, poor bioavailability adversely impacts the efficacy of a nutrient, often requiring larger doses of the active ingredient to achieve the intended effect. Poor bioavailability can lead to: 

• Increased risk of gastrointestinal irritation due to usage of larger amounts of active nutrients. This, in turn, can place a heavier load on the liver and potentially increase side effects.  
• At times, the body might not absorb or use the nutrient, regardless of the amount taken. Such conditions significantly undermine the nutrient’s therapeutic benefits.  

Factors Affecting the Bioavailability of Nutrients

The bioavailability of most nutrients is affected by several factors, including the physical properties of the nutrient itself. Some nutrients have significant absorption and bioavailability challenges, and conventional approaches fail to harness their therapeutic potential. 

Al Czap, CEO of Tesseract Medical Research, founder of Thorne Research, and a pioneer in nutritional supplement formulation, explains that if a product is not soluble, then it gets broken down and the byproducts sit in the digestive tract until they are excreted. 

“In the absorption of things, it is all about solubility.”— Al Czap, CEO of Tesseract Medical Research

The following are key factors impacting the bioavailability of nutrients:

• Concentration of nutrients: The concentration of nutrients in food depends on several factors, such as cooking and processing methods and the presence of anti-nutrients, all of which affect bioavailability.
• Dietary factors: The type of food matrix and amount of dietary fat influence the absorption of nutrients, as certain nutrients require fat for optimal uptake.  
• Chemical forms: A nutrient’s chemical form’s stability, lipophilicity, solubility in the digestive environment, and ionizability significantly influence its bioavailability.  
• Supplements taken naturally from meals: Natural supplements and nutrients, such as vitamins C and D, quercetin, piperine, and other flavonoids, can enhance the absorption and bioavailability of specific nutrients.   
• Nutrition and health of the individual: An individual’s age, gender, physiologic state, dietary preferences, and health conditions impact a nutrient’s bioavailability. 
• Nutrient-nutrient interactions: Some nutrients can enhance or inhibit the absorption of other nutrients. For example, having a low calcium level can lower the bioavailability of vitamin B12. 
• Excretory losses: The rate at which a nutrient is metabolized and excreted from the body also influences its absorption and bioavailability. 

Water-Soluble Nutrients versus Fat-Soluble Nutrients

Nutrients are broadly classified as water-soluble and fat-soluble. Notably, water-soluble nutrients are particularly challenging to make bioavailable because of: 

• Extreme dilution: Body fluids’ high water content significantly dilutes water-soluble nutrients, affecting their targeted delivery and chances of accumulation in specific tissues. 
• Rapid excretion: Water-soluble nutrients are rapidly excreted out of the system.
• Increased reactivity: Water-soluble vitamins, such as B-complex vitamins and vitamin C, are highly sensitive to external conditions like temperature, light, pH, moisture, and oxygen, all of which can lead to degradation during processing and storage. 

Formulations often use increased amounts of active ingredients to counter these factors. The following table highlights the drawbacks of increasing the amount of active ingredients in a supplement formulation.

In comparison to water-soluble nutrients, fat-soluble nutrients more easily cross cell membranes. They are absorbed by fat globules and are stored in tissues. According to Czap, if a nutrient is fat-soluble, then one should find a way to make it attractive to the body to achieve better absorption. However, the fat solubility of a nutrient doesn’t guarantee the body will be able to utilize it. We will discuss how different practices can address these challenges in the following sections.

Mineral Salts: The Conventional Approach to Enhancing Bioavailability of Nutrients

A supplement’s bioavailability is largely influenced by the nature of the delivery mechanism embedded within the formulation. Mineral salts are used as the most popular and conventional delivery vehicles in supplement formulations because of their:  

• Palatability: Mineral salts tend to be palatable.
• Ease of usage: Mineral salts are easy to press into tablet format and readily mix with the compounds necessary to achieve fat solubility. 

Mineral salts, however, can prevent the active ingredients from being immediately dissolved and unintentionally exposed to mucosal surfaces. As a result, the mineral salt hinders the nutrients’ bioavailability, and most supplement formulations are unable to achieve the nutrient’s desired absorption and bioavailability.

How Nanotechnology Enhances Bioavailability of Supplements

An advanced delivery system beyond traditional formulations is critical in generating a high bioavailability supplement. In recent years, the development of delivery systems supported by nano-machinery and nano-technology has opened new techniques for enhancing the bioavailability of supplements. Various novel pharmacological approaches are being explored to enhance the bioavailability of nutrients, including:

• Microcapsules: The active nutrient is packaged within a second material (lipids, proteins, polysaccharides) to protect its integrity during transit through the stomach. 
• Solid dispersion systems: The solubility of a nutrient that is poorly soluble in water is enhanced by enveloping it in a hydrophilic carrier to increase its surface area, solubility, and dissolution rate.  
• Nanoparticles: Nanoparticles can be tailored to carry multiple nutrients in a single formulation, enhancing their bioavailability, solubility, and retention time. 
• Nano-liposomes: Lipid-based nanocarriers enhance the bioavailability and enable the controlled release of the encapsulated hydrophobic nutrients.  
• Cyclodextrin inclusion compounds: The cyclic oligosaccharides produced from starch or starch derivatives are a breakthrough in nutrient delivery, achieving optimal solubility, stability, and bioavailability of nutrients.  

In the following section, we highlight the functioning and advantages of cyclodextrin and how it enhances supplement bioavailability. 

What is Cyclodextrin?

Cyclodextrin is a group of molecules attached in the shape of a ring. Cyclodextrin can be used as fiber in the body, which means it can be pressed into tablets or capsules alone or alongside traditional fillers, such as mineral salts. 

How does Cyclodextrin Work? 

A cyclodextrin structure works like a padlock, only opening to release the substance inside when it encounters the corresponding “key”—the cellular feature that is the intended target of the therapeutic effect. Because only the intended target is exposed to the active ingredient, it leads to superior efficacy, minimal side effects, and tunable duration of the supplement formulation. 

What are the Advantages of Cyclodextrin? 

Cyclodextrins overcome the challenges of poor absorption and bioavailability of nutrients. The following are key advantages of cyclodextrins embedded in supplement formulations. 

• Making nutrients tolerable: Nutrient molecules such as glutathione, butyric acid, and curcumin, which historically had too many off-target effects to be therapeutically tolerable, can now promote different health functions.  
• Delivering nutrients in small amounts: Bioactive nutrients can be delivered in smaller amounts than previously required, with fewer nutrient particles wasted on incorrect targets. 
• Targeted delivery of nutrients: The nutrients encapsulated in cyclodextrin are typically fat-soluble, which enables them to permeate cell membranes after they reach their intended destination. Targeted delivery increases the efficiency of the nutrients by preventing them from drifting away from their target.

Notably, water-soluble nutrients don’t form complexes with cyclodextrin as easily as do fat-soluble nutrients. Water-soluble nutrients are repelled by molecular forces when they approach the cyclodextrin. Ongoing research is developing water-soluble nutrient complexes in cyclodextrin. 

An Innovative Nutrient Delivery System for Unprecedented Absorption of Nutrients

Tesseract Medical Research utilizes a proprietary CyLoc® —DexKey® nutrient delivery system that enhances the absorption and bioavailability of nutrients. The cyclodextrin-based smart delivery system makes it possible to absorb conventionally difficult-to-absorb molecules, such as glutathione, berberine, and curcumin. 

Tesseract’s transport system protects nutrients from early breakdown, while masking any unpleasant taste and odor. Each nutrient molecule is isolated in a dextrin fiber matrix, creating nano-sized particles that are easily absorbed and utilized by the cells. The CyLoc® technology surrounds each insoluble and poorly absorbed nutrient molecule in its smart delivery system to maintain each nutrient molecule’s integrity during transit through the stomach. The accompanying DexKey® reactors release each nutrient molecule at the desired point in the intestinal tract, thus enhancing its absorption and bioavailability. 

The power of Tesseract lies in its Three Pillar Approach to enhance the bioavailability of supplements.

• Optimal absorption: The advanced nutrient delivery system enhances the absorption and bioavailability of nutrients through targeted delivery. 

• Palatable ingredients: The smart delivery system transforms nutrients, such as curcumin, berberine, and butyric acid, into palatable ingredients for better patient compliance. 

• Micro-dosing: The unprecedented absorption of nutrients results in using lower doses of active ingredients to yield the desired rapid physiological response. 

Tesseract’s proprietary nutrient delivery system enhances supplement bioavailability, thus achieving the therapeutic benefits of the active ingredients.  

Citations:

¹Coelho SC et al. Foods. 2022;11(9):1271.

²Arshad R et al. Food Sci Nutr. 2021;9(6):3354-3361.

³Esteso M et al. Int J Mol Sci. 2024;25(8):4547.