In February, Nestlé Health Science, a subsidiary of Nestlé, bought another U.S. medical food company, Covington, LA-based Pamlab, which produces prescription medical foods that support patients with conditions like dementia, diabetic peripheral neuropathy, high-risk pregnancies and depression. Nestlé’s strong commitment in this domain is exemplified by a series of other acquisitions, including Accera, a firm producing medical foods for the dietary management of Alzheimer’s patients;  Vitaflo, which provides nutritional solutions for those effected by genetic disorders influencing how the body processes foods; and Prometheus Laboratories, a firm specializing in diagnostics and pharmaceuticals in gastrointestinal (GI) and oncology.

Medical food or Food for Special Medical Purposes are principally formulated food products intended to be used under the supervision of medical and other appropriate health professionals (e.g., dietitians, nurses and pharmacists). These products assist the dietary management of individuals (including children) with chronic disease, disorders or medical conditions, or during acute phases of illness, injury or disease states.

FDA on Medical Food
The U.S. FDA designates medical food as a category of substances intended for the clinical dietary management of a particular condition or disease. Specific criteria necessary to receive this FDA designation include that the product must be:

• A specifically formulated food for oral or enteral ingestion;
• For the clinical dietary management of a specific medical disorder, disease or abnormal condition for which there are distinctive nutritional requirements;
• Made with Generally Recognized As Safe (GRAS) ingredients;
• In compliance with FDA regulations that pertain to labeling, product claims and manufacturing.

As a therapeutic category, medical food is distinct from both drugs and supplements. Labels must include the phrase, “to be used under medical supervision,” as medical foods are produced under rigid manufacturing practices and maintain high labeling standards.

Major Health Condition Targets
From a medical standpoint, an increasing prevalence of diseases such as metabolic syndrome, irritable bowel syndrome (IBS), lactose intolerance, Alzheimer’s disease and food intolerances are continuously being targeted in medical food development. Age-related digestive tract diseases as well as general digestive issues and absorption of nutrients are additional areas of focus for many companies.

According to Vladimir Badmaev, MD, PhD, head of R&D at NattoPharma ASA, Oslo, Norway, “The most popular categories of medicinal food address aging populations and wasting conditions like muscle wasting or sarcopenia, bone rarefaction or osteoporosis, health conditions caused by insufficient status of vitamins and minerals and gastrointestinal dysbiotic conditions.”

Zak Dutton, president, Prismic Pharmaceuticals, Scottsdale, AZ, added, “there are now medical foods available for a wide range of medical conditions from osteoarthritis to Alzheimer’s disease.” 

The field of candidates for development into medical foods is expanding continuously due to advances in the understanding of nutrition and disease, coupled with developments in food technology increasing the number of products that can be formulated and commercialized. Over the last three years, SKIM, a Switzerland-based company, has been involved in more than 30 market research projects in the medical food area to help treat or prevent a vast range of conditions—from more severe (diabetes, oncology) to less severe conditions (allergies, sarcopenia, loss of energy, etc.), mostly for multinational companies.

Nutrition’s Role
The majority of U.S. medical food products (51 of 82) on the market are for metabolic diseases. Protein-based medical foods are the most common. Nutrients such as omega 3s, isoflavones, vitamin D, chelated zinc, flavonoids (e.g., baicalin, catechin, pterostilbene), chromium picolinate, phytosterols and L-arginine are other leading ingredients used in this developing category, along with other vitamins and minerals such as pyridoxine, thiamine and folic acid, which are being used in combination.

BioStrategies Group, Chicago, IL, counts a total of 23 firms with products on the U.S. medical foods market—four larger companies, which also account for the bulk of revenue, and 19 smaller firms. Manufacturers are bringing more products to market that address metabolic processes. In 2006, Limbrel (flavocoxid), the first medical food for the management of osteoarthritis launched. Axona was deemed by FDA in 2009 as a medical food, targeting metabolic deficiencies associated with Alzheimer’s disease; the well-researched VSL #3, a probiotic for ulcerative colitis and ileal pouch, hit the market in 2002. NiteBite, a snack bar for the nutritional management of hyperglycemia, has been marketed since 1996.

Other health platforms include osteopenia/osteoporosis (Fosteum, Primus Pharmaceuticals), depression (Deplin, Pamlab), sleep disorders associated with depression (Sentra PM, Targeted Medical Pharma) and pain and inflammation (Theramine, Targeted Medical Pharma).

In recent years, Theramine, an amino acid formulation, was developed and used as a prescription medical food for the clinical dietary management of the metabolic processes associated with pain and inflammation. The formulation is GRAS-approved and designed to increase the production of serotonin, nitric oxide (NO), histamine and gamma-aminobutyric acid by providing precursors to these neurotransmitters. The neurotransmitters addressed in this formulation have well-defined and specific roles in the modulation of pain and inflammation.

DeplinR (Pamlab) or l-methylfolate is described by the manufacturer as “an orally administered prescription medical food for the dietary management of suboptimal folate levels in depressed patients.”

New dietary options are needed to improve compliance with a low-phenylalanine diet and subsequent metabolic control for individuals with phenylketonuria (PKU). A variety of acceptable, nutritionally complete products can be made from whey protein glycomacropeptide (GMP) with the potential to replace, or partially replace, the traditional amino acid-based medical foods currently used in PKU diets. GMP-based medical foods represent a new paradigm to move current PKU diets from synthetic amino acids as the primary source of protein equivalents to a more physiologically normalized diet based on intact protein, which research demonstrates improves protein use and promotes satiety (Calcar & Ney, 2012. J. Acad. Nutr. Diet).

NuMe Health LLC, a new biotechnology company based in New Orleans, LA, is developing evidence-based prebiotic supplements for specific health conditions. Proliant Health and Biologicals has announced recently self-affirmed GRAS status for the company’s proprietary, trademarked ingredient ImmunoLin (bovine globulin concentrate). “The market for food and nutrition products that support gut health and immunity are expanding rapidly,” said Eric Weaver, chief scientific officer with Proliant. “The formal approval allows the use of ImmunoLin in products requiring GRAS such as functional foods and beverages, meal replacement and medical foods.”

Prismic’s new product, NEUREPA (eicosapentaenoic acid), is a prescription medical food intended for the dietary management of omega 3 deficiency in patients with schizophrenia, bi-polar disorder and depression. It is a proprietary, highly purified omega 3 triglyceride formulation containing not less than 92% EPA per 1 gram. 

NattoPharma has developed up to 98% pure, natural vitamin K2, MK-7 (MenaQ7 brand) in crystal form to prevent osteoporosis and supports cardiovascular health in postmenopausal women.

Another candidate product in this segment is alpha-cyclodextrin. The unique structure of this dietary fiber allows it to form a stable, non-digestible complex with dietary fat. Just as the fiber-fat complex is non-digestible it is also non-fermentable, thus eliminating messy side effects. Graham Birch, vice president of sales and marketing with Soho Flordis International (SFI), a Sydney, Australia-based natural medicine company, said that FBCx is a patented alpha-cyclodextrin-based soluble dietary fiber with the unique ability to bind and eliminate nine times its own weight in dietary fat. Several positive clinical outcomes from randomized, placebo-controlled trials demonstrated its health benefits as a medical food. SFI has recently introduced Calorease weight management with the patented FBCx fat binder in the North American market.

Challenges to Success
In 1988 FDA made steps to encourage the development of the medical foods category by awarding products orphan drug status. These regulatory changes reduce the costs and time associated with bringing medical foods to market, as beforehand medical foods were treated as pharmaceutical drugs.

Zak Dutton of Prismic broke the challenges down into two broad categories. “The first relates to the development of a medical food. Unlike dietary supplements, medical foods require strong scientific support to meet the medical food criteria. This means the benefits of the medical foods have to be proven in clinical trials. The second challenge is relative lack of awareness or understanding of medical foods in the medical community. Most doctors in the U.S. have not heard of the term ‘medical food’ and don’t know that it is a distinct, FDA-regulated category. As a result, there is a tendency to think of medical food as either a drug or as a dietary supplement.”

Dr. Badmaev of NattoPharma echoed the same view. “The challenges to efficacious medicinal foods stem from regulatory obstacles that can be resolved by a solid research program and formulation of the active ingredients, like vitamin K2, into a stable, nutritious and attractive form of food delivery.”

“Companies developing medical nutrition solutions as a part of the treatment and prevention of chronic diseases like diabetes, sarcopenia, HIV and obesity face several challenges,” according to Benoît Gouhier, project director of SKIM consumer health. He also highlighted that “most health services and insurers currently don’t cover the cost of nutritional products for disease prevention or management. As such, consumers and patients become the final decision makers regarding the purchase of these products, often guided by the advice and recommendations of healthcare professionals. The result is a complex and competitive environment and decision-making process that poses real challenges for marketers.”

The Market’s Future
The medical foods category is relatively well known in the U.S., but less so elsewhere. Mr. Dutton of Prismic Pharma offered his take on future development. “My expectation is that the category in the U.S. will grow significantly. There is simply too great a need from both the health benefit and cost of healthcare perspectives.” 

“The trend in medicinal food started approximately 15 years ago and since then the body of clinical peer-review papers on the subject has grown dramatically,” Mr. Badmaev of Natto Pharma added.

The actual size of the medical food market is unclear. FDA predicts strong growth, in light of the increasing use of medical foods in long-term care and the growing population of older individuals. Global sales have been projected at just less than $9 billion (Global Industry Analysts, 2011). The lack of an industry association and scarcity of public data make it difficult to estimate U.S. medical food revenue; the best estimate is $2.1 billion for 2011 growing at approximately 10%, according to bioStrategies Group.

Regulatory Considerations
In the U.S., medical foods are a special product category regulated by FDA. In Europe, a similar category called “Foods for Special Medical Purposes” (FSMPs) is covered by the Foods for Particular Nutritional Uses directive and regulated by the European Commission (EC).

Medical foods do not require FDA pre-approval for marketing in the U.S. Unlike dietary supplements, which are restricted from making disease claims and are intended for healthy individuals, medical foods are intended for specific disease populations.

Disease claims must be supported by sound scientific evidence substantiating claims of successful nutritional management of the disease. All ingredients must be approved food additives or classified as GRAS. Reimbursement for medical foods is inconsistent, and varies by product and by health plan. Like medical foods in the U.S., FSMPs are intended for use only under medical supervision, but they must comply with EC regulations. In the EU, while there is harmonized legislation on health claims, compounds, ingredients and plants are still regulated only at a national level.

“Prismic is not experiencing any major regulatory challenges at this stage, nor do we anticipate any as we launch NEUREPA later this year,” said the company’s Mr. Dutton. “Regulatory issues tend to arise when a company is trying to take advantage of the regulations or has not done the necessary work to ensure their products meet the strict criteria for medical foods.”

Dr. Badmaev also suggested the same approach of pursuing a convincing research program to overcome regulatory challenges.

Business Model & Market Positioning
Medical food marketers used varying call points by their sales force and the distribution channels for their products, often using a combination for each. The call points include: primary care physicians, specialist MDs and prescribing nurses, registered dietitians, mail order pharmacies, long-term care (corporate and/or local), hospitals (corporate and/or local) and home care services. Main distribution channels include retail and mail order pharmacies, doctors’ offices, Internet, hospitals, home care services and specialized disease clinics.

Market positioning of medical food can be challenging. Many marketing gurus suggested the following steps for successful positioning:

• Raise awareness for a new category to physicians, patients and payers;
• Successfully leverage “consumer pull” and “healthcare professional push” by building targeted strategies for disease-specific medical nutrition;
• Create new adherability such as taste, smell, color, mouth feel and presentation to differentiate medical foods from prescription drugs. “Naturalness” of a medical food is also another key element to building a position statement.

Safety Profiles
The popularity of food supplements and medical foods, resulting in a billion-dollar market in the U.S., reflects not only the societal trend away from “artificial” pharmaceutical drugs and toward “natural” ingredients, but also the lack of satisfactory drugs that are both effective and safe.

Consumers are likely to assume that medical foods are safe, but some recent studies suggest this may not always be true. Flavocoxid, which is marketed as a medical food, is a proprietary blend of purified, plant-derived bioflavonoids. It is believed to act as a dual inhibitor of cyclooxygenase and 5-lipoxygenase enzymes, and therefore inhibits the conversion of arachidonic acid into both prostaglandins and leukotrienes. These mechanisms make flavocoxid an interesting therapeutic alternative to nonsteroidal anti-inflammatory drugs.

Because it is classified as a medical food, flavocoxid was marketed beginning in 2004 in the absence of any published randomized trial. Although two trials became available in 2009 and 2010, four cases of acute liver injury associated with flavocoxid have been reported (Reichenback & Juni, 2012, Ann. Intern. Med.). Some herbal products used as food supplements or medical food, as well as vitamins, antioxidants, fiber, trace elements, proteins and amino acids, can also be associated with liver injury.

Technological Challenges
The creation of a medical food with potential health benefits for a particular patient population is a surprisingly complex process. Fortunately, the developmental process for a specific medical food is not as rigorous or as tightly regulated as that of a pharmaceutical agent. However, numerous factors unique to the enteral formulation of a new product come into play, such as physical/chemical compatibility, pH, stability, bioavailability, decay and even palatability.

Additional considerations such as strength of health benefit claims, packaging or presentation and marketability will ultimately determine commercialization potential and whether a product ends up being released to the public. A full understanding of the development, substantiation and commercialization of a medical food is necessary for important physiologic concepts in nutrition therapy to end up as part of the therapeutic regimen at the bedside of the critically ill patient.

Conclusion
Taking a nutrition product from the bench to the bedside is a long and complex endeavor. However, to understand the effectiveness and safety of any healthcare intervention—drug, medical device, food supplement or medical food—clinical evidence from well-designed randomized trials and observational studies will always be necessary. Given the widespread use and potential side effects of medical food and food supplements, marketing strategies for these products in the absence of clinical evidence should be reconsidered.

Research is limited on the medical properties of food, particularly human clinical studies. More work is needed to understand the potential for medical foods, specifically, more prospective, controlled studies; larger subject populations; and longer treatment durations.

In addition, besides food, research is needed to advance the technology used to deliver certain medical foods such as tubing and pumps.    

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Dilip Ghosh, PhD, FACN, is director of nutriConnect, based in Sydney, Australia. He can be reached at dilipghosh@nutriconnect.com.au; www.nutriconnect.com.au.