Invented by Mark Puder, Bruce Bistrian, Childrens Medical Center Corp, Beth Israel Deaconess Medical Center Inc
The Childrens Medical Center Corp, Beth Israel Deaconess Medical Center Inc invention works as followsDietary formulations are available in oil emulsions that provide total parenteral and enteral nutrition or as food oils suitable for oral administration. These formulations contain approximately 2-60% calories of C20 or longer omega-3 fat acids and about 0.05 to 1% calories of arachidonic. The formulations provide less than 1% total calories from linoleic and alpha-linolenic acids and the fatty oils provide 5-60% of the total calories. The dietary formulations can also be used to treat certain diseases and conditions.
Background for Dietary formulations for treating inflammation and other disorders.
Linoleic acid (and alpha-linolenic) are two fatty acid that can’t be synthesized by human beings. These fatty acids are essential fatty acids (EFAs) for human nutrition. Through enzymatic deaturation and extension principally by liver, linoleic acid (and alpha-linolenic acids) form polyunsaturated fat acids of the omega-6 and omega-3 series. Although man and other mammals are capable of reducing or lengthening fatty acid chains, they cannot convert fatty acids from one group to the next (e.g. Omega-6 to Omega-3 Both linoleic as well as alpha-linoleic have been included in all Total Enteral and Parenteral Nutritional products.
It is recommended that 3 percent of total calories be from linoleic acids in the United States. Linoleic acids should be consumed at a level of 1% to 2 percent of total dietary calories. This is sufficient to prevent biochemical and clinical evidence for deficiency in many animal species as well as humans. According to the Academy of Pediatrics, infant formulas should contain at least 2.7% of linoleic acids (Recommended Dietary Allowances, 10th Edition, 1989, Authors: Subcommittee on RDA’s Food and Nutrition Board Commission on Life Sciences; Publishers: National Academy Press Washington, D.C.).
Essential fat acids play an important role in many metabolic processes. There is evidence to suggest that low essential fatty acid levels or the wrong mix of essential fatty oils may be a factor for a variety of illnesses, including metabolic syndrome, heart disease and obesity.
It is therefore important to gain a better understanding of essential fatty acids and how they affect nutrition so that we can design better nutritional programs.
Paraenteral nutrition (PN), a life-saving treatment for patients who are unable to absorb enteral nutrients due to insufficient intestinal function or length, is available. Patients with inadequate gastrointestinal absorptive functions died often from starvation and other complications of malnutrition before the invention of PN. More than 30,000 Americans are dependent on PN to survive today. However, long-term PN use can lead to many complications such as bloodstream infections, metabolic abnormalities, and organ dysfunction. Our team has found that PN-associated liver diseases (PNALD) is the most common complication in children. This is at least partially due to the lipid emulsion ingredient3. Although increasing the enteral energy intake and reducing PN is the best treatment for PNALD, this is often difficult when intestinal function is poor5.6 Sometimes, liver dysfunction can lead to intestinal failure. In these cases, liver-small intestine transplantation is the only option. If infants are not able to wean themselves off PN or do not receive a liver/small-bowel transplant, their mortality rate is close to 100%. Evidence suggests that PNALD could be partly due to the high lipid content of soy oils, which are rich in pro-inflammatory omega-6 fat acids and hepatotoxic phytosterols 8. A fish oil-based lipid solution has been proven to be effective in treating PNALD in children3, 4, 10 and 11.
The present invention is based on the observation, that linoleic acids, contrary to what we know, is not an essential fatty acid. Linoleic acid should not be included in parenteral or enteral nutritional products that provide full nutrition. According to the invention, only minimal amounts of arachidonic acid (a downstream product) of linoleic acids are necessary for good nutrition and prevention essential fatty acid deficiencies. These minimal amounts of arachidonic acid reduce inflammation and are a pro-inflammatory substance. A nutritional product that contains no linoleic acids will reduce arachidonic acid without causing inflammation or essential fatty acid deficiencies. This will improve the immune response to infection.
Accordingly, the invention provides a diet formulation in the form an oil emulsion providing total or parenteral nutrition or in the form a food oil suitable to oral administration. It contains about 2-60% calories of a C20- or longer omega-3 fat acid and about 0.05%-1.1% calories of arachidonic acids. The formulation has less than 1% total calories from linoleic and alpha-linolenic acids and provides 5-60% of the total calories.
In one embodiment, the diet formulation contains 0.15% -0.30% calories of arachidonic acids or 0.15 – 0.6% calories of archidonic acids.
In one embodiment, the C20 omega-3 fatty oil consists of eicosapentaenoic (EPA), docosahexaenoic (DHA), or eicosatetraenoic (EICOSATETRAENOIC acid (DHA), as well as 5-docosapentaenoic and combinations thereof. It contains about 0% calories of omega-6 fatty oils other than arachidonic acids, about 0% calories of linolenic and about 0% calories of alpha-linolenic and about 0 by calories from alpha-linic acid. The preferred ratio of C20 and longer omega-3 fat acids to arachidonic is between about 10:1 and about 40:1. The ratio could be as low as 10:1, 20:1, 30:1, 40:1, etc.
In one embodiment, the arachidonic acid is provided as dihomo-gamma-linolenic acid or gamma-linolenic acid which is converted in vivo to arachidonic acid, wherein the dihomo-gamma-linolenic acid or gamma-linolenic acid is provided in amounts of 0.45% to 6.0% by calorie.
In one embodiment, the C20 (or longer) omega-3 fatty acids are selected from the group consisting eicosapentaenoic Acid (EPA), docosahexaenoic Acid (DHA), and mixtures thereof.
Another aspect is a dietary formula for total enteral or parental nutrition, or a supplement that provides restricted omega-3 or omega-6 oil delivery to an individual. The omega-3 or omega-6 fatty acids are one or more C20 omega-3 fatty oils or longer, as well as arachidonic acid.
In one embodiment, the C20 and longer omega-3 fatty acids are eicosapentaenoic (EPA), docosahexaenoic (DHA) or 5-docosapentaenoic (or combinations thereof).
In one embodiment, the ratio between omega-3 fatty acids and arachdonic is approximately 10:1 to 40:1. The ratio could be as low as 10:1, 20:1, 30:1, or 40:1. One embodiment of arachidonic acids is equal or lower than about 2.7 kilocalories/kg for an adult or 9 kilocalories/kg for an infant or child.
In one embodiment, the supplement or dietary formulation further contains additional components like one or more omega-9 fat acids (e.g. Linoleic acid), a source carbohydrate, a protein source, and an emulsifier.
In one embodiment, the omega-3 fatty acids and arachidonic are obtained from fish, fungal oil, or genetically modified plants that produce arachidonic or immediate precursors to arachidonic, e.g. Gamma linolenic, and dihomogammalinolenic acids.
In one embodiment, the diet formulation also includes a source for carbohydrate. Any simple or complex carbohydrate can be used as a source of carbohydrates, such as monosaccharides or disaccharides. One embodiment of the carbohydrate source is corn starch and dextrose, glucose, corn starch and dextrose, and corn starch and dextrose.
In one embodiment, the diet formulation also includes a source for protein. Any protein hydrolysate, peptide mixtures, or amino acid mixtures with high biologic values can be used as a source of protein. A protein hydrolysate may be partially hydrolyzed in the natural environment and contain a significant fraction of variable-chain length peptides (e.g. medium and short chain peptides), but less than 10% free amino acid, and more preferably less that 5% free amino acid. One embodiment hydrolyzes only high biological value proteins, such as whey and lactalbumin. Other embodiments do not use lactose and are therefore preferably free of amino acids.
In one embodiment, the diet formulations also contain a source for vitamins and minerals. Vitamins and minerals may be in accordance with or roughly the Recommended Dietary Allowance, now known as the Daily Reference Intake (DRI). Nucleotides and beta-carotene, taurine, and carnitine can all be found in dietary formulations that do not meet the RDA.
In one embodiment, the diet formulation also contains an emulsifier and/or other inactive ingredients like artificial sweeteners or flavoring.
The dietary formulations described in the invention can be used as a dietary supplement (food oils) or as a total or parenteral feeding regime. One embodiment of the dietary formulation is a complete parenteral formulation. Another embodiment of the formulation is a total enteral formulation that can be used for oral or tube feeding. Another embodiment of the dietary formulation includes food oil in an oral form. If the dietary formulation is intended for parenteral or total enteral feeding, it should contain all essential amino acid and essential vitamins and minerals. This will ensure that the patient receives all nutrients. The formulation that is a dietary supplement (food oils) should contain approximately 5-60% of the total energy expenditure in calories.Click here to view the patent on Google Patents.