Today because of tools capable of probing the details of metabolism, we are able to study the utilization of amino acids in specific, physiologically important processes. Such information may lead to recommended dietary allowances for each amino acid specific for subpopulations and perhaps individuals. These new findings identify the metabolic end-products of some amino acids as crucial intermediates in the maintenance of a variety of physiological functions that bear no direct relationship to protein metabolism. The precursor amino acids for these intermediate compounds are either non-essential or conditionally essential and thus may play a specific, non-protein, role in amino acid requirements in individuals close to nitrogen equilibrium. Thus, combinatorial nutrition or composition of amino acids blend is clearly the optimal approach for nutritional support of the catabolic patient. In summary, our bio-scientists determined it is optimal to produce our proprietary blends with all 20 identified amino acids with specific higher concentrations of key amino acids for specific dietary supplement targets, such as immune system support, mental health support, etc…
AmCaid's proprietary blends are as followed,
AmCaid Product Development History:
- Our proprietary blends of combinations of Amino Acids that our physicians, clinicians & bio-scientists found to be optimal for
targeted nutritional supplements.
- Our proprietary blends have been proven to be completely stable
(without easily breaking down) when used with Pfizer's proprietary
transport media & liquid capsulation.
- Due to the previous reason (b), our blends are the only ones in
the market that offer Amino Acid supplements with the 4-6 times
better absorption than any other Amino Acid products being offered.
- Our proprietary blends have been proven to highly stable for
extended shelf life without requiring additional fillers or additives
(preservatives). Thus, they allow us to stay true to be completely
In 1996, AmCaid was started by a network of research physicians, clinicians, bio-scientists and professional business associates. Our initial products were powder-based products, which were messy, wasteful, tasted awful with very
In 2001, we replaced our powdered-based products with tablets, which were full of fillers, preservatives still with poor absorption.
Starting 2002 until now, after years of research and product testing and development with Pfizer scientists' collaborations, we finally replaced our tables with liquid vegie capsules, Pfizer's latest liquid capsule technology, to stay true to our mission to be completely "natural." Liquid capsules provide our products with maximum absorption without additional fillers or preservatives, and no unpleasant taste. This increases client compliance due to being easier to swallow, and clients taking less pills, yet getting better results, and paying much less than previous technologies.
Combinatorial nutrition is state of the art in terms of an understanding of the physiology and biochemistry of protein, peptide and amino acids in enteral nutrition. Through careful clinical investigation, how this knowledge can best be exploited for optimizing the design of the protein/peptide/amino acid component of nutrition formulations. In doing so it should be possible to achieve a more effective use of proteins, peptides, and amino acids in the comprehensive clinical management of individuals under various pathophysiological states.
Amino acids have been and will always be an integral part of nutritional support in all patients. The beneficial use of specific amino acids in pharmacologic doses indicates that combinatorial blend conditionally essential. As knowledge of the altered regulation of amino acid metabolism in patients improves, the design of more effective feeding regimens was done where the goal is to provide the best nutrition to all patients at all times.
Altered intakes of various amino acids modulate the rates of the major systems (protein synthesis, protein degradation, and amino acid oxidation) responsible for the maintenance of organ and whole-body protein and amino acid homeostasis. For oxidation amino acid availability is a primary determinant and protein synthesis is affected particularly at the initiation phase. The remains are about amino acid-dependent changes in mRNA synthesis, processing, turnover, and translation. The relationships between protein and amino acid intake and components of whole-body protein and amino acid kinetics are considered with reference to nutritional adaptation and accommodation. The limit of adaptation to protein intake cannot be lowered substantially beyond that for healthy adults whose habitual protein intake is generous. Metabolic control theory should be considered in the interpretation of results of studies dealing with amino acid requirement estimations.
Nutrients regulate amino acids metabolism both in an acute fashion and on a long-term basis. The ingestion of combinatorial blends is associated with a dramatic switch from an overall catabolic state to a state of net protein anabolism. The acute response of protein metabolism is mediated, in part, by an increase in insulin secretion, itself a consequence of glucose absorption. Whereas insulin may primarily suppress rates of proteolysis, amino acids are responsible for the stimulation of protein synthesis that follows food intake. In the long run, the effects of nutrition on protein metabolism depend on the energy supply, the source of the supply (carbohydrate versus fat) and dietary amino acids/protein intake.
Modern infant formulas contain sufficient indispensable as well as dispensable amino acids to support normal growth of both term and preterm infants. However, current parenteral and specialized enteral amino acid preparations do not appear to be optimal. Many of the problems with parenteral preparations reflect the fact that ingested amino acids (protein) undergo more extensive enteric and hepatic metabolism than parenterally administered amino acids, including conversion to other amino acids (e.g. arginine) that reach the plasma for support of ongoing protein synthesis. Because this important source of amino acids is bypassed when nutrients are delivered parenterally, parenteral requirements of these amino acids are increased. In addition, while ingested phenylalanine and methionine appear to be converted to tyrosine and cysteine, respectively, it seems that parenterally administered phenylalanine and methionine are not. While glutamine, the branched-chain amino acids and arginine appear to be important in stressed infants and infants with compromised gastrointestinal function, specific roles have not been defined. Finally, because some amino acids are insoluble (e.g. tyrosine) and others are unstable in aqueous solution (e.g. glutamine and cysteine), suitable ways to provide these amino acids are needed. Soluble of amino acids blends has been shown to be both efficacious and safe in adults. This is also likely to be true for pediatric patients as well.
Basic concepts of amino acid nutrition are summarized and quantitative amino acid requirements of different types of pathophysiological states based on current knowledge of "conditionally indispensable" amino acids and organ-specific requirements for amino acids are the result. The concepts of nitrogen balance, limiting amino acid, protein utilization, protein efficiency ratio, and amino acid score for determining protein quality are reviewed. Problems in assessing efficiency of nitrogen utilization when single amino acids or amino acids in combination with balanced diets are used as therapeutic agents are discussed in relation to the potential roles of the branched-chain amino acids, arginine, and glutamine in trauma and as immunostimulators.
Short-term balances and metabolic studies suggest that current estimates of adult indispensable amino acid (IAA) requirements are too low. In addition, the observed biological value of protein is less than that predicted from its amino acid score. These discrepancies reflect the fact that IAA requirements are complex. This is because consumption of protein usually results in oxidative losses of IAA and nitrogen, which are important to the organism and variable according to dietary composition. It is likely that the current values for IAA requirement primarily reflects different dietary designs in the original balance studies, which induced different rates of oxidative losses. A new model for amino acid utilization is proposed which takes account of such losses, and factors that influence them. The IAA requirements (R) can only be unambiguously defined in terms of Rmin, a value obtainable under artificial conditions when oxidative losses, Lr, are minimal (Lr min); current estimates of adult requirements may be close to this level. An operative requirement of practical value, Rop, will only be defineable when the value to the organism of the oxidative losses induced by usual diets, (Lr op), can be evaluated.
AmCaid's model for dietary IAAs allows for diurnal cycling of body protein, in which oxidative losses of amino acids occurring during the postabsorptive phase must be balanced by net protein deposition during feeding if overall balance is to be attained.
Liquid Delivery Technology and Absorption
"You are what you eat" statement is no longer true in the eye of a nutritionist, but rather "you are what and how much your body can actually absorb."
Oral bioavailability is a term where a product in take by the mouth is available for usage by the body. The absorption of drugs from the gastrointestinal mucosa, which is the most common and convenient route for drugs delivery, is one of the important determinants for oral bioavailability. However, macromolecular drugs such as peptides and proteins are unable to overcome the mucosal barriers and/or are degraded before reaching the blood stream. Unfortunately, most if not all of the OTC's protein and amino acid products are based on powder or encapsulated powder, which get degraded very readily. Unprotected amino acid powder and in a drink hardly able to survive through the stomach HCl's content. Recent studies shown that its survival rate of these products through the stomach is about 10 % that is even before any kind of intestinal absorption lost is added. Encapsulated enteric coat capsule survival rate through the harsh stomach environment is better but when the contents of the capsule is released into the intestine, there is not proper delivery system available to ensure its maximum absorption
For this simple fact is why we formulated our superior products using our evolutionary delivery system.
Our amino acid blends are formulated to aid intestinal mucosa in the catabolism of amino acids for maximum absorption.
The small intestine is not only responsible for terminal digestion and absorption of nutrients, but it also plays an important role in catabolism of arterial glutamine and dietary amino acids. Most of glutamine and almost all of glutamate and aspartate in the diet are catabolized by small intestinal mucosa, and CO2 accounts for 56-64% of their metabolized carbons. The small intestinal mucosa also plays an important role in degrading arginine, proline and branched-chain amino acids, and perhaps methionine, lysine, phenylalanine, threonine, glycine and serine in the diet, such that 30-50% of these dietary amino acids are not available to extraintestinal tissues. Dietary amino acids are major fuels for the small intestinal mucosa and are essential precursors for intestinal synthesis of glutathione, nitric oxide, polyamines, purine and pyrimidine nucleotides, and amino acids (alanine, citrulline and proline), and are obligatory for maintaining intestinal mucosal mass and integrity. Because intestinal amino acid catabolism plays an important role in modulating dietary amino acid availability to extraintestinal tissues, it has important implications for the utilization efficiency of dietary protein and amino acids in animals and humans.
Furthermore, physiological mechanism of gastrointestinal absorption of amino acids is dose-dependent (Matsuka's studies from Nagoya City University, Japan). Therefore our proprietary amino acid blends have been carefully chosen to enhance maximum absorption
Choose a proper transport medium to increase maximal absorption
Recent introduction of molecular biological techniques resulted in the successful identification of drug transporters responsible for intestinal absorption of a wide variety of drugs. Each transporter exhibits its own substrate specificity, though it usually shows broad substrate specificity. By selecting the right transporter, it is possible to eventually develop products with ideal pharmacokinetic profiles and/or improving oral bioavailability.
The contribution of physicochemical descriptors to lipophilicity, water solubility, and intestinal absorption and oral bioavailability in humans is considered. Partitioning in the octanol/water system is presented as a competition between two opposing effects: volume and hydrogen bond acceptor ability. Water solubilities of liquid compounds are roughly equal to their reciprocal logP values. However, there is also a detectable contribution of H-bond donor ability to water solubility. The main problem in predicting the solubilities of solid chemicals and drugs is the estimation of their crystal lattice energies. QSAR approaches that add terms such as melting point, and the product of H-bond donor and acceptor parameters are not sufficient to make these predictions practical. Since human intestinal absorption for passively transported drugs is almost completely correlated with hydration processes that are determined by H-bond acceptor and donor abilities, liquid technology is chosen.
Our amino acid proprietary blends and our delivery technology enable us to supply amino acids at an 85 to 90% maximal absorption rate. Almost 4 years after AmCaid has worked with Prizer's scientists, our delivery system is supported by the most recent study published in December of 2004 done by scientists at Department Pharmacy and Pharmaceutical Technology, University of Santiago de Compostela, Spain. This affirmation assures the consumers that they are receiving the best possible amino acid dietary supplement products available in the market today.
Additional References and Articles:
- Biologically active dietary peptides. Mini Rev Med Chem. 2004 Oct;4(8):815-21.
- Effect of chain length on absorption of biologically active peptides from the gastrointestinal tract. Digestion. 1999 Jul-Aug;60(4):332-7.
- Mechanism of action and control in the digestion of proteins and peptides in humans. Arq Gastroenterol. 1999 Jul-Sep;36(3):139-47.
- Digestion and absorption of dietary protein in man. Proc Nutr Soc. 1980 Feb; 39(1):61-70.
- Protein digestion and amino acid and peptide absorption. Proc Nutr Soc. 1985 Feb;44(1):63-72.
- Uptake and fate of absorbed amino acids and peptides in the mammalian intestine. Fed Proc. 1986 Jul;45(8):2261-7.
- Mechanisms of absorption of amino acids and oligopeptides. Control and implications in human diet therapy. Arq Gastroenterol. 1999 Oct-Dec;36(4):227-37
- Intestinal absorption of protein hydrolysis products: a review. J Anim Sci. 1990 Sep;68(9):3011-22.
- General discussion of peptide transport in bacteria and the mammalian gut. Ciba Found Symp. 1971;:145-50.
- Digestion and absorption of dietary protein in man. Int J Vitam Nutr Res Suppl. 1983;25:39-54.
- Membrane digestion and peptide transport. Ciba Found Symp. 1971;:123-43.
- Digestion and absorption of protein. Mayo Clin Proc. 1973 Sep;48(9):624-9.
- Intestinal mucosal amino acid catabolism. J Nutr. 1998 Aug;128(8):1249-52
- Intestinal absorption of peptides. Biochem Soc Trans. 1983 Dec;11(6):808-10
- Dietary bioactive peptides. New Horiz. 1994 May;2(2):237-43
- Digestion and absorption of protein. Annu Rev Med. 1978;29:99-116.
- Intestinal absorption of peptides.
Physiol Rev. 1975 Oct;55(4):537-608
- Exp Gerontol. 2004 Nov;39(11-12):1731-8
- Biopharm Drug Dispos. 1998 Oct;19(7):465-72.
Tablet & capsule trends: an overview of the latest developments.(Tablet & Capsule Trends)(Cover Story)
Nutraceuticals World; 1/1/2004; Madley-Wright, Rebecca
Tablets, capsules and soft gels represent a basic need to the nutraceuticals industry. However, most experts would agree that these delivery vehicles are anything but basic. Indeed, these formats require precise engineering and development to get consumers the nutrients they need in order to maintain optimal health.
Trends & Issues
Tablets, capsules and soft gels have undergone several significant transformations over the years, resulting in improved formulations and delivery of ingredients. The increasing consumer demand of dietary supplements, which brought in $18.7 billion in sales in 2002, according to Nutrition Business Journal, San Diego, CA, has forced a competitive environment for companies vying to meet varied consumer needs by making slight alterations to existing products.
Discussing this trend was Bill Chekan, global director of marketing, Capsugel, Greenwood, SC. "In the battle for market share, particularly when the product lines of many nutraceutical companies include the same product (i.e., glucosamine, gink-go, MSM, etc.), there has been heightened activity to show that the dosage form itself is a form of differentiation," he said. "At a 'tactical' level, labels that used to simply say '60 capsules' now say things such as '60 Easy-to-Swallow Capsules,' '60 Enterically Coated Capsules,' or '60 Vegetarian Liquid-Filled Capsules.'"
Additionally, as pointed out by Marco Bootz, sales and marketing manager, Gum Base, Lainate, Italy, the growing popularity of supplements has also pushed companies to make these products more pleasant to consume. As a result, companies have strengthened their positions by building brands that distinguish their products from others out there, a challenge made increasingly urgent if their patents are expiring or can be bypassed. "Increasing functional product lifecycles through brand extensions and brand innovations is one tactic being pursued," Mr. Bootz said. "But another major tactic is looking at new vehicles for delivering existing functional products. The selection of the delivery system has to be done on a case-by-case basis through the evaluation of the total product concept. In the end, however, the objective still needs to be to deliver an enjoyable experience to consumers."
At Arizona Nutritional Supplements (ANS), Chandler, AZ, Greg St. Clair, president, said he has seen requests come in that run the gamut. "ANS has seen an increase in requests for unique forms of tablets and capsules," he said. "The developments in aqueous-based coating systems have led to an increase in the amount of unique color coatings requested. In addition, requests for vegetarian products have increased leading to use of more vegetarian capsules and use of excipients, which meet vegetarian standards. Lastly, there has been an increase in the availability and requests for liquid capsules."
Discussing trends in all three segments--tablets, capsules and soft gels--was John Altenberg, vice president--Marketing, Leiner Health Products, Carson, CA. "Tablets are still the dosage form of choice for supplements in general due to price and familiarity. If a company brings forth a product in a tablet and then introduces it in a soft gel, consumers may not want to pay the premium," he explained. "However, for the fat-soluble ingredients such as CoQ10, fish oils and vitamin E, soft gels are the preferred form of delivery and continue to do well." He added, "Some people shy away from capsules because of potential tampering issues. However, I know there is technology now where the capsules can be heat sealed to minimize tampering. In addition, I believe two-piece capsules are still the dosage form of choice when it comes to herbals because they capture the value and benefit of the whole herb."
Mr. Altenberg also discussed the issue of compliance, singling out "swallowability" as a barrier for some dosage forms. "Swallowability is still a big issue with larger tablets and soft gels," he said, adding, "Also, consumers do not comply with directions that advise them to take a certain amount of pills throughout a given day. Asking consumers to take two to three pills a day of a particular product is a very difficult proposition with respect to dietary supplements. Some products lend themselves very well to once-a-day dosing but others are more challenging."
The issue of compliance was also highlighted in the 2003 Health & Wellness Trends report published by the Natural Marketing Institute (NMI), Harleysville, PA. According to the report, 17% of consumers are dissatisfied with the quantity of pills they take, while 17% claim to have difficulty swallowing pills/capsules. As a result, almost a quarter (23%) prefer to get their supplements in other forms besides pills or capsules. That said, tablets, capsules and soft gels still lead the pack in the dietary supplement arena with a majority of consumers still preferring to get their supplements in these formats--tablets (66%), capsules (65%) and soft gels (60%).
Another trend, according to Mr. Chekan, points to the use of new or novel nutraceutical products, where the "protective" aspects of the dosage form play a strong functional role. For example, he said, some extracts of natural products derived from fruits and vegetables require protection against oxidation during manufacture, shipment and storage. Additionally, he said, such novel extracts may be sensitive to moisture. In such cases, the selection of the right dosage form is critical to maintaining product stability and performance.
Dosage Form Developments
Companies are experimenting with innovative means of delivery on a regular basis. One company that has been busy researching how its product could play a part in the supplement market is Gum Base. Mr. Bootz explained, "Companies exploring innovations in functional products are taking a closer look at our compressed powder gum concept as a viable delivery system because it allows for easy and pleasant administration of active principles, and makes them easier to consume at any time."
At the heart of this approach, said Mr. Bootz, is chewing gum that can be manufactured in powder form to which active principles can be added and compressed into tablets--ready to be coated and/or packed. In addition, Mr. Bootz said, "Gum is particularly suitable for a pleasant, sub-lingual absorption of actives. When low temperature processing is needed to accommodate the use of active principles that are heat-sensitive, including bioactives and phytochemical components, compressed gum is an appropriate vehicle."
Another advantage of Gum Base's technology, according to Mr. Bootz, is that it allows functional products to be tailored to individual brands and flavors, giving the manufacturer a greater amount of flexibility. And manufacturing the compressed powder gum is relatively hassle-free. "Launching compressed gum products can be an easy operation since (with some technical support and adaptations) conventional tablet presses can be used for production--a very important consideration when 'time to market' is key," said Mr. Bootz.
Liquid-filled dosage forms are growing, as consumers inherently relate "liquids" with positive perceptions of faster acting, and easier and gentle absorption, according to Capsugel's Mr. Chekan. "Liquids typically allow 'combination' products to be formulated easier," he said. "Furthermore, fast-melt formulas, which do not require water for administration, certainly have appeal for pediatric and geriatric populations, where swallowing can be problematic."
The Potential GMP Impact
Mr. Bootz of Gum Base said the proposed GMPs (good manufacturing practices) would impose stricter controls on raw materials and finished products in terms of identification, quality, purity, composition and strength. In addition, he said the degree of impact would depend on the size of the company. "The companies that would most be affected by these new requirements would most likely be smaller companies that need to put more quality checks in place. In general, larger companies already apply these guidelines," he said, adding, "But overall, the effect will be positive since everyone will be following the same guidelines, creating more of a level playing field in the market. Furthermore, the resulting stricter regulation and control can be expected to raise consumer confidence and lower skepticism regarding quality and validity of new functional products coming to market."
Capsugel's Mr. Chekan offered his perspective on the potential GMP impact. "Long term, from a dosage form perspective, one potential impact will be that dissolution issues related to over-compressing of tablets will not be as prevalent as today," he said. "Also, tablet-manufacturers will likely stress the use of formulations that require less chemical binders and fillers to minimize the investment in GMP documentation and validation resources." He continued, "For capsule companies, who have already implemented GMP controls to meet the needs of pharmaceutical customers, there may be a need to expand the capability of their quality systems in order to meet a wider array of individual customer requirements."
To ANS' Mr. St. Clair, the finalization and implementation of the proposed GMPs will be one of the most important issues companies will face in 2004. "The biggest issue we will see this year, which dominated last year as well, is the finalization and implementation of the new GMPs," he said. "ANS and others within the industry have been asking for enforceable standardized GMPs for a considerable time. Some manufacturers have raised the bar for quality standards and have voluntarily taken part in GMP certifications offered by groups like NSF and the NNFA; but as long as others are allowed to not follow GMPs, the rest of the industry suffers."
Mr. St. Clair said it is difficult to speculate as to what the finalized GMPs will look like. However, he said, the need for comprehensive testing of raw ingredients will surely be an integral part. "Having an in house laboratory will be crucial to success in the future," he explained. "ANS' testing capabilities include high performance liquid chromatography (HPLC), FT-IR spectrometer, thin layer chromatography (TLC), gas chromatography, microbial analysis, friability, moisture analysis, disintegration, dissolution and stability. Regardless of the final form of the GMPs, it is important that manufacturers can be assured they are meeting the proper specifications for the products they manufacture."
Of major concern to ANS and numerous industry groups, according to Mr. St. Clair, was the amount of duplicate testing required above and beyond what is required for the manufacturing of drugs. "Many of the formulas out on the market have complex matrices of multiple ingredients, which can be incredibly costly and, in some cases, impossible to test in finished form," he said. "GMPs that are stricter than those in place for pharmaceutical products would have the effect of unnecessarily raising costs to the consumer and could unfairly deprive customers of many specialized formulations."
Richard Salzstein, pharmaceutical sales and marketing manager, Aqualon Division of Hercules Inc., Wilmington, DE, said he believes that the quality aspect of tablets and capsules will take a larger command of R&D and manufacturing with the focus on GMPs and the constant need for cost-effective and general cost improvement. "GMPs will indeed require some companies to improve their processing and documentation to ensure quality products compete," he said. "Manufacturing will no longer be considered at the end of the line for product development in some houses, but will be an integral part in the product development lifecycle, knowing the requirements for GMP and cost-effectiveness. This could cause a shake-up in some production units but the strong will survive for the industry good."
It is hard to make predictions about the future, especially with finalized GMPs for dietary supplements being a huge question mark at the moment. However, Capsugel's Mr. Chekan offered a few predictions. "Future drivers of capsule preference will likely remain intact. Health conscious consumers tend to be well informed, and they will remain sensitive to avoiding the added sugars and starches that can be associated with chemical-based tableting agents," he said. "Other considerations that will continue to drive capsule preference include ease-of swallowing, as well as an elegant visual appearance."
Aqualon's Mr. Salzstein believes the industry will continue to trend toward ever-larger active doses in individual tablets and capsules. "This mounts a manufacturing challenge, which I find a good one for Aqualon," he said. "We provide efficient tablet binding with our Klucel Nutra[TM] modified cellulose tablet binder. As in the pharmaceutical industry, nutraceutical producers have embraced the ability to provide smaller tablets with efficient low-volume binders, displacing larger volumes of less efficient binders and fillers."
Mr. Altenberg feels the future for dietary supplements hinges on improving compliance. "Glucosamine and chondroitin started out as six pills a day and now it's down to two pills a day to get the same amount of active ingredients," he said. "There is always going to be a convenience factor that will be important to supplement manufacturers and although the industry has made considerable progress, there is still a long way to go. Clearly one pill a day dosing is the ultimate goal."
This article in a nutshell:
COPYRIGHT 2004 Rodman Publications, Inc.
- Trends and issues in tablets, capsules and soft gels
- Dosage form developments
- The potential GHP impact
- Predictions for the future