The new frontier in technology may well be at the invisible depths of about 1000^th the thickness of a human hair. Called nanotechnology, this hot research and development area is already making an impact on nutrition and food despite the infancy of supporting science. These days, technology moves quickly, and it is hard for the average businessperson, formulator, regulator and consumer to keep up with the mechanisms of action, safety, science and scope of breakthroughs such as the nanoworld.

Ask three experts to define nanotechnology, and youll get three slightly different answers. However, the average answer is that nanotechnology is the manipulation of particles at a size between 1 and 100 nanometers for the purposes of novel applications and benefits. A nanometer (nm) is on the level of the size of many molecules. For perspective, a molecule of gold is 0.33 nm; the head of a pin is about 1 to 2 millimeters (mm), which is 1 million times larger than a 1 to 2 nm particle.

One of the advantages of materials of this size, called nanomaterials, is when gathered in bulk, they offer more surface area¾a million 1 nm spheres have more surface area exposed than does one 1 mm sphere of the same nutrient. This theoretically increases the availability of this nutrient to the medium. The other primary advantage of nanomaterials is their small size can afford them increased access to places in the body, as membranes designed to block out naturally larger-sized particles a human typically takes in are unable to reject the nanosize nutrients.

However, these potential advantages are also potential dangers, as scientists are not yet certain just how various nanomaterials will behave when they cross membranes such as the blood-brain barrier, or when they are inhaled during production. Likewise, many nanoparticles could end up in the environment, where their impact is a similar unknown.

In life, unknown often drives fear. The mystery of nanotech may be non-threatening when used in the areas of energy, machinery and structural materials; people look at technology differently when it comes to their own well-being. While it is too early to tell whether consumers are mostly fearful of nanotechnology in food, beverages, medicines and dietary supplements, recent surveys show consumers are alarmed to ask for more information.

A late-2009 report from the Woodrow Wilson Project on Emerging Nanotechnologies (PEN) highlighted results of a national survey on adults conducted by Hart Research Associates. Public awareness of nanotechnology increased during the past year to 2006 levels, which still equates to about 7 out of 10 U.S. adults having not heard or learned a single thing about nanotechnology. They also largely feel the well-known federal agencies FDA, EPA and USDA should regulate such technologies when it comes to ingestible products. In fact, the report found the public trusts these agencies to manage risk more than the companies engaging in such technological manufacturing.

As the primary regulator of dietary supplements and food products, FDA is the agency that matters most to the natural products industry. FDA has not created its own definition of nanotechnology, but it defers to the definition (similar to the above) developed by the National Nanotechnology Initiative (NNI), a cooperative effort by FDA and 22 other federal agencies on research and development in nanoscale science, engineering and technology.

In the little guidance it has provided, FDA has noted products will be regulated according to their normal statutory category (food, drug, supplement, etc.), not according to any technology used. Despite advice from a PEN report that FDA require premarket notification for any nanotech dietary supplement ingredient¾a suggestion rebutted by the Council for Responsible Nutrition (CRN)¾the agency, at this point, has not required such notification, nor does it consider nanosized ingredients as new dietary ingredients (NDIs) requiring notification. FDA experts have indicated nanotech products under its regulation will be handled on a case-by-case basis. FDAs Vasilios Frankos, Ph.D., CFSAN, told an audience at SupplySide West 2008, Las Vegas, FDA believes more data may be needed to demonstrate the safety and effectiveness of a material that is reduced to nano size, and the agency would determine whether a products regulatory status would change due to the use or presence of nanomaterials in a dietary supplement.

On foods, CFSANs Annette McCarthy, Ph.D., has reported the safety of a given compound in a food will not automatically apply to a nano version of the compound, due to possible novel properties and characteristics. She further noted insufficient scientific data prevents FDA from extending GRAS (generally recognized as safe) status of an ingredient to its nano-sized version. Also, any change to the chemical attributes, intended use, GMP production or quality of a nano-sized food ingredient will affect its compliance with regulations.

Nonetheless, the regulatory environment surrounding all the different types of nanomaterials in the natural products industry is in a state of flux, with nano-sized bits of info (nanoinfo?) on current and likely future considerations continuously released from the mouths of various regulators. Each month or season there is often a different outlook, so the best anyone can say is that regulation of nanomaterials and nanotechnology in foods and dietary supplements is being developed behind closed doors at FDA, EPA and other agencies. FDA has indicated a guidance document from the agency on nanotechnology will be made public in 2010. Until then, the nutshell is that nanotech food additives and colors must be tested for safety and toxicity.

However, companies need to realize the EU, Canada and the State of California have all requested information from manufacturers of nanoscale products.

Nano Market Data

Just as safety data can be scant and inconclusive, solid market data on nanotechnology and nanomaterials used in food or dietary supplements can be elusive. Many companies simply do not report the presence or use of nanostuff in their products, and the arbitrary application of a 100 nm limit in size included in most definitions of nanotechnology exclude products that may still act nano-like. Still, reports have begun to surface, trying to pin down some parameters of various nano markets.

Overall, market research firm RNCOS projected the market for nanotechnology into consumer products to grow at an adjusted annual growth rate (AAGR) of 9.4 percent between from 2005 to 2010. It expected Asia-Pacific to be the most active region in nanotech product sales, with the United States and Europe trailing. This data ties in with various surveys showing Asian consumers are more aware and accepting of nanotechnology than are Americans and Europeans.

Segmenting into foods/beverages, dietary supplements and personal care/cosmetics, providing market numbers gets even trickier. There are no real numbers on any nanosupplement market, but PEN has listed at least 40 dietary supplements known to contain nanotech or nanomaterials, noting this reflects a tripling since 2007. The incorporation of nanotech in supplements appears to focus on delivery systems, which can often present opportunities to develop intellectual property for the companies involved.

Despite PEN listing dietary supplements as one of its top two product categories, there seems to be a greater effort to generate market data on nanofoods. Helmut Kaiser Consultancy (HKC) has reported more than 180 food-related applications are in different developmental stages, with a few such applications already on the market. It projected the nanofood market to rocket from $7.0 billion (USD) in 2006 to $20.4 billion in 2010. More than 200 companies around the world are today active in research and development, according to HKC, which added the United States is currently the leader followed by Japan and China; by 2010 Asia, with more than 50 percent of the world population, will be the biggest market for nanofood, led by China.

The Cientifica consultant firm has sought to clarify nanotech in the food industry, explaining of the trillion-dollar food market¾packaging, processing, safety and additives and not agriculture¾nanotech only accounted for about $410 million (USD) in 2006, with a predicted increase to $5.8 billion by 2012. In fact, they say there is very little food with nanotech ingredients on grocery store shelves today.

There might be more nanotech found in food packaging. Innovative research and products (iRAP) suggested the three basic categories of nanotechnology applications and functionalities are in the development of food packaging: the enhancement of plastic materials barriers, the incorporation of active components that can deliver functional attributes beyond those of conventional active packaging, and the sensing and signaling of relevant information.

According to iRAP, nanotech applications in the food and beverage sector are now emerging, but will grow rapidly in the coming years. Applications in this area already support development of improved tastes, color, flavor, texture and consistency of foodstuffs, increased absorption and bioavailability of nutrients and health supplements, new food packaging materials with improved mechanical, barrier and antimicrobial properties, and nano-sensors for traceability and monitoring the condition of food during transport and storage, the group said.

In hard numbers, the total nano-enabled food and beverage packaging market was $4.13 billion in 2008, but is expected to grow to $4.21 billion in 2009 and $7.30 billion by 2014, a compound AGR (CAGR) of 11.65 percent. With $2.7 billion in 2008, active technology represents the largest share of the market, followed by intelligent packaging ($1.03 billion) and controlled release packaging ($360 million). The firm predicts the active segment will remain the largest through 2014, with $4.35 billion in sales, and the intelligent segment will grow to $2.47 billion in sales.

Within the segments, oxygen scavenger, moisture absorbers and barrier packaging are tops among active technologies, with more than 80 percent of the current market, while antioxidant (60 percent) and antimicrobials (40 percent) dominate controlled release.

iRAP further reported active packaging is already being successfully applied in the United States, Japan and Australia to extend shelf-life while maintaining nutritional quality and ensuring microbiological safety. Examples of commercial applications include the use of oxygen scavengers for sliced processed meat, ready-to-eat meals and beer, the use of moisture absorbers for fresh meat, poultry and fresh fish, and ethylene-scavenging bags for packaging of fruit and vegetables.

The other PEN top nano product category is cosmetics and sunscreens, for which there are more than 600 products recorded that use nanotechnology. Market research firm Frost & Sullivan attributed the recent uptick of specialty chemicals in personal care products largely to the nanotechnology boom. The use of nanotechnology greatly contributes to the advantages of creating safer and more nature-friendly ingredients in personal care products, the firm stated.

Research and Technology Development

Nanotechnology can rear its head in food, supplements and cosmeceuticals in many different ways. In food, nano is more easily used in the cultivation, processing, production or packaging of food items. In nutrient delivery, the focus is on improving bioavailability and stability and protecting sensitive nutrients (moisture, oxidation, etc.).

One of the oldest and most popular ways to incorporate nanotech into nutrition is via micelles, the tiniest of capsules that form naturally when nature requires a fat-soluble substance to be soluble in water. The micelle is basically a cavity that is water-soluble outside, but fat-attracting inside. Micelles help emulsify or dissolve fat in water solutions (such as fat globules in milk) and absorption in the intestines of fat-soluble nutrients such as vitmains D, E and K, coenzyme Q10 (CoQ10), carotenoids and essential fatty acids (EFAs). Based on this natural nanotechnology, many nutrition manufacturers are developing and incorporating novel micelle nanotechnologies in their products.

Bruce Lipshutz, a professor of chemistry at UC Santa Barbara, and his research team have been investigating improved CoQ10 bioavailability via nano-micelle-forming technology. They form a 25 nm diameter micelle that has fat-soluble vitamin E as its lipophilic (fat-loving) center. When CoQ10 is introduced, it goes straight to this center, resulting in a clear, nano delivery of CoQ10 that is stable at room temperature. Lipshutz noted this micelle delivers twice the amount of CoQ10 into the bloodstream and can work also for nutrients like omega-3s, carotenoids (lutein and beta-carotene) and resveratrol.

Yoav Livney and his team from Israel institute of Technology, Haifa, have come up with similar results using casein micelles as nanoencapsulates for delivery of hydrophobic nutrients to enrich non-fat or low-fat food products. Such nano-capsules may be incorporated in dairy products without modifying their sensory properties, they concluded, adding casein micelles may be useful as nano-vehicles for entrapment, protection and delivery of sensitive hydrophobic nutraceuticals within other food products.

Qingrong Huang, associate food science professor at Rutgers University, also focuses his research on nanoencapsulation of nutraceutical ingredients, with an emphasis on improving body absorption and circulating time of phytochemicals (flavonoids). Although there are abundant dietary supplements available in tablet forms, their water solubility and oral bioavailability are very poor, Huang said, noting the potential of nanoemulsions and nanoencapsulation to successfully solve this problem. The main public concern is safety. However, we havent found any evidence of safety problem for our nanoemulsion, nanodispersion and polymer micelle-based encapsulated flavonoids/carotenoids. Certainly, more investments are needed to carry out thorough animal and clinical studies on nanoencapsulated phytochemicals.

Germany-based Aquanova is among the companies listed by PEN as offering nanotech supplements. Nanotechnology itself, from our understanding, is well-accepted by consumers in the field of technical applications, especially when surface protection or surface quality is concerned, said Frank Behnam, Aquanova. We do not see nanotechnology to be or to become part of foods, and beverages, but of course nanoscaled structures like micelles have been and always will be part of colloidal systems, which also are used in foods and beverages.

Behnam confirmed his companys NovaSOL® line features this micelle delivery technology to improve bioavailability or to protect sensitive ingredients from oxidation. He said although these structures are on a nanoscale, they do not rely on nanotechnology in the engineered science manner. Moreover colloidal nanoscaled structures are understood as being nature-like, self-assembly systems, he added.

Behnam noted a scientific expert working group, comprised mostly of university food science professors form Germany, sent its consensus to EU authorities, recommending regulators consider colloidal systems such as liposomes and micelles have been used safely for decades and are naturally occurring nanocasules that should not be regarded the same as engineered nanomaterials for scientific and regulatory purposes.

Israel-based Nutralease uses micelles in its patent pending NSSL (nano-sized, self-assembled liquid) delivery system for vitamin E, omega-3s, beta-carotene, lycopene, isoflavones, CoQ10 and lutein. These ingredients are not only used for both dietary supplements, but also for cosmeceuticals, in topical applications that are bioavailable, stable and clear.

University of Monash, Australia, professors Ian Larson, Ph.D., and Ken Ng, Ph.D., are researching and developing chitosan-based biopolymers to encapsulate and protect antioxidants from the low pH ins the gut, so they can make it to the small intestines and be released in a controlled manner. He explained the biopolymers stick to the walls of the small intestine, where they leak the antioxidants directly into the cells through which absorption takes place. In addition to improving the absorption rate of catechins, which is only as high as 1.1 percent in regular delivery, the researchers noted this technology could help incorporate ingredients like omega-3s in baked goods such as breads.

Nanotechnology is hard to see, define and quantify in a market sense. Naturally occurring nanotech such as micelles and liposomes may seem innocuous for use in making certain safe nutrients such as vitamins, omega-3s and other antioxidants more bioavailable and stable, but when it and other forms of nano are applied to more potent dietary supplement ingredients, where these nano-enabled substances will go in the body and how they will affect health is still largely unknown. This lends to a fear by regulators and consumers, bothwhich have been slow to earn about nanotech. It is truly an infant frontier that hopefully does not become another cowboy-filled Wild West the natural products industry does not need.