Recipient Organization
COLORADO STATE UNIVERSITY
(N/A)
FORT COLLINS,CO 80523
Performing Department
Health & Exercise Science
Non Technical Summary
The number of overweight/obese people in the US is greater than the entire combined population of the United Kingdom, Germany and France. As a consequence of excess fat, many of these overweight/obese US adults are highly likely to develop a cardiovascular and/or metabolic disease, such as hypertension, type 2 diabetes, or dyslipidemia. In theory, increased daily physical activity combined with moderate dietary restriction would prevent/reverse obesity and the associated disease risk, however long-term success/compliance with these intervention strategies is notoriously poor. Perhaps as a consequence of this poor compliance, and the perceived perception as a suitable diet/exercise alternative, the US nutritional health supplement industry has enjoyed enormous economic growth; in 2010 the annual sales were estimated to be $28 billion. Despite this economic success, the health supplement industry continues to be the subject of serious criticism in both the scientific and lay-media. The stated conclusion of a well-publicized Annals of Internal Medicine editorial, titled "Enough Is Enough: Stop Wasting Money on Vitamin and Mineral Supplements" was, while most supplements are ineffectual, some are actually harmful. More recently, the office of the New York State Attorney General reported on laboratory analysis of store brand dietary supplements, revealing that many products do not contain the advertised ingredient(s). In light of the poor long-term compliance with diet and exercise, and the widespread preference for what appear to be potentially harmful, unregulated health supplements, the need for rigorous scientific evaluation of supplements is critical. Two supplements that have tremendous potential for providing protection from obesity associated metabolic and cardiovascular diseases are curcumin and resveratrol. Based on studies in isolated cells and animal models, these nutraceuticals, both individually and in combination, offer protection from insulin resistance, vascular disease and cancer. Unfortunately, when translated from cell and animal experiments, the human data pertaining to curcumin and resveratrol are less impressive, and somewhat inconsistent. The major limitation of these nutraceuticals for human use appears to be poor absorption and low bioavailability. That is, human digestion is such that we are unable to effectively transport curcumin and resveratrol out of the gut and into the blood for systemic distribution. Direct intravenous infusion of curcumin and resveratrol would bypass the limitation of intestinal absorption but infusion is an impractical mode of administration for the general public, and also carries a risk of infection, discomfort, and phlebitis. Accordingly, an alternative mode of effective curcumin and resveratrol delivery is of obvious interest. In this regard, oral consumption of curcumin and resveratrol encapsulated in liposomes may hold promise.Liposomes are manufactured microscopic, hollow spherical vesicles composed of a lipid bilayer. When loaded with pharmaceuticals, liposomes are a very effective method of drug delivery. If ingested, the pharmacokinetic properties of liposome intestinal absorption override the usual absorption pattern of the encapsulated drug. That is, the delivery of a drug with a typically slow pattern of absorption may be accelerated when encapsulated within a liposome. Consistent with this idea, the first aim of proposed study is to compare, in humans, circulating concentrations of curcumin and resveratrol following oral ingestion of curcumin and resveratrol encapsulated within liposomes, and oral ingestion of un-encapsulated curcumin and resveratrol. Based on our preliminary data and experience with liposomal delivery, we hypothesize that ingestion of curcumin and resveratrol encapsulated within liposomes will evoke greater circulating concentrations than ingestion of an equivalent un-encapsulated dose. Further, to investigate a functional implication of enhanced delivery, the second aim of the proposed study is to determine, in humans, if liposomal encapsulated curcumin/resveratrol provides superior resistance to high-fat, over-feeding induced insulin resistance. Consistent with increased bioavailability, we hypothesize that liposomal curcumin/resveratrol will provide superior protection compared with un-encapsulated curcumin/resveratrol.
Animal Health Component
60%
Research Effort Categories
Basic
40%
Applied
60%
Developmental
0%
Goals / Objectives
1) To compare, in humans, circulating concentrations of curcumin and resveratrol following oral ingestion of curcumin and resveratrol encapsulated within liposomes, and oral ingestion of un-encapsulated curcumin and resveratrol.2) To determine, in humans, if liposomal encapsulated curcumin/resveratrol provides superior resistance to high-fat, over-feeding induced insulin resistance.
Project Methods
Insulin sensitivity (oral glucose tolerance), body mass and composition (dual energy x-ray absorptiometry), and circulating concentrations of curcumin and resveratrol (standard analytical chemistry procedures) will be determined at baseline, after 21 days of administration of a dietary supplement (placebo, curcumin combined with resveratrol, or curcumin combined with resveratrol encapsulated within a liposome), and after 7 days of overfeeding and administration of a dietary supplement.