* Please Note: This information is based partly on Traditional Medicine which uses natural materials to support health. This information has not been evaluated or approved by the FDA. These statements have not been evaluated by the Food and Drug Administration (FDA). These products are intended to support general well being and are not intended to treat, diagnose, mitigate, prevent, or cure any condition or disease. If conditions persist, please seek advice from your medical doctor.
Description
What is Celadrin®?
Celadrin® achieves maximum efficacy for joint mobility and health by managing the entire range of inflammation from painful joints (osteoarthritis, tendonitis, bursitis, muscle and deep tissue pain) to psoriasis. This amazing substance is a medically and clinically proven pain management compound that is safe to use with no known side effects, reducing inflammation and pain quickly. Celadrin® provides a new and different anti-arthritic action. However it may be used along with other natural joint health supplements such as Glucosamine Sulfate, Chondroitin Sulfate, or MSM, empowering them to perform faster and more efficiently in building joint cartilage.
Celadrin® is a proprietary blend of natural, esterified fatty acids and synergists. It provides fast relief for painful joints and muscles by halting production of compounds that cause pain and inflammation.
For 50 years the Webber name has been trusted in North American households as the source of Vitamin E. Now Webber Naturals is a 'natural' extension, bringing consumers a wide range of vitamins, minerals, herbs and special supplements to meet their families' health and nutrition needs.
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Label Information
Hermetic seal under cap for safety and freshness. Contains no artificial preservatives, color, dairy, sweeteners, starch, wheat or yeast.
For product freshness protect from humidity.
Additional Information
SOURCE
Celadrin is the proprietary product of Imagenetix of San Diego, CA. Celadrin is a blend of fatty acid esters produced from cetyl alcohol and fatty acids from bovine tallow fat [steric acid (C18:0), oleic acid (C18:1), palmitic acid (C16:0), palmitoleic acid (C16:1), myristic acid (C14:0), myristoleic acid (C14:1), lauric acid (C12:0), decanoic acid (C10:0)]. [Tallow fat is the nearly colourless and tasteless solid fat extracted from the natural fat of cattle, sheep, etc, used in making candles, soap, and lubricants.]
USES
Celadrin is used for reducing joint pain associated with inflammation, and for improving joint functional performance in osteoarthritis (OA).
In osteoarthritis, Celadrin should be considered a synergistic treatment with glucosamine and chondroitin sulfate to enhance the reduction of pain and inflammation. Celadrin should not replace glucosamine, or the glucosamine and chondroitin sulfate combination. Both glucosamine and chondroitin sulfate are endogenous mediators of joint structure and performance. In most cases of age-related osteoarthritis, a decline in tissue levels of glucosamine and chondroitin sulfate is thought to be an etiological factor, presenting a biological rationale for continued supplementation along with synergistic treatments.
Celadrin may be used in rheumatoid arthritis (RA) to determine whether or not it can reduce RA suffering. In the early stages of RA, Celadrin may be effective. There are no published clinical trials to inform the RA patient about the probability of success, as there are with osteoarthritis.
RECOMMENDED AMOUNT
Use 2 softgels of 350 mg BID. (See Rationale for Dosage in the Pharmaceutical Commentary Section.)
ADVERSE SIDE EFFECTS
There are no reported adverse side effects with Celadrin in the published clinical investigations of its efficacy and safety in human patients.(1-5)
Celadrin has been safely used orally for up to 68 days,(2) and topically for up to 30 days with applications twice a day.(3,5)
Based on the general absence of reported post-marketing adverse effects, Celadrin is not expected to be associated with adverse effects when it is used according to the recommended daily amounts.
Allergic reactions to Celadrin may be possible in the susceptible person, as with any substance.
INTERACTIONS
To date, there are no reported adverse drug or food interactions with Celadrin.(1) Celadrin is expected to enhance pain and inflammation control when it is used with glucosamine, or the glucosamine and chondroitin sulfate combination.
PRECAUTION / CAUTIONS
Keep Celadrin out of the reach of children to avoid consumption as candy.
CONTRAINDICATIONS
Do not use Celadrin during pregnancy or during the breast-feeding period since the full effects of these preparations on a developing fetus or newborn are not known.
PHARMACEUTICAL COMMENTARY
Celadrin is a novel, safe, and clinically demonstrated anti-inflammatory substance that has the ability to significantly reduce pain in a variety of conditions associated with inflammation and produce a clinically significant enhancement in joint performance.(2-5) The clinical investigations of Celadrin indicate that it can be positioned as an effective and safe option to over-the-counter NSAID's,(2) which are well recognized to present a risk for adverse gastric and kidney effects, and in some cases may exert adverse effects directly on cartilage, particularly if NSAID treatment is prolonged.(6)
The biological rationale for using cetylated fatty acids as anti-inflammatory and anti-arthritis treatments developed originally from the observation that Swiss albino mice possess a natural resistance to laboratory induced polyarthritis when subjected to Freund's adjuvant agent, an internationally standardized research solution for inducing inflammation and polyarthritis in test animals.(7) The natural resistance to inflammation in this species has been shown to be mediated by endogenously produced cetyl myristoleate.(7) Celadrin presents a wider spectrum of cetylated fatty acids.
Normally the introduction of fatty acids into the body whether by diet or pharmaceutical products would be expected to increase the chance for the formation of lipid peroxidation products if sufficient antioxidants like vitamin E are not also present. While esterification of the Celadrin fatty acids is thought to be essential for its beneficial pharmacological effects, esterification of fatty acids also protects them from inadvertent lipid peroxidation.
The absorption of the cetylated fatty acid complex found in Celadrin is thought to be virtually complete, whether administered orally or topically, and distributed within the various tissues, as determined by radiolabel research in male Wistar rats.(8) The majority of Celadrin is thought to be processed in the liver, with only a relatively small amount of intact cetylated fatty acid remaining. The observed beneficial effects of cetylated fatty acids are assumed to be due to tissue accumulation in cell membranes. The distribution of cetylated fatty acids is through chylomicrons.
Clinical Outcomes with Celadrin
The most common symptoms of osteoarthritis are pain and stiffness, with an associated reduction in joint range of motion. Accompanying pain and stiffness are limitations to normal activities of daily living, such as getting up from a chair, walking, balance (ie, greater postural sway), and using stairs.(3) It has been shown that quadriceps strength, joint pain, perceptions of functional ability, and body weight can predict between 39 to 56 percent of the variance in the time required to perform various functional tasks.(3,9) Thus, an intervention that targets pain reduction and performance functional improvements is necessary in order to improve the quality of life of patients with osteoarthritis.(3)
To date, there are four published clinical investigation that demonstrate the efficacy of Celadrin for pain reduction and functional improvements in osteoarthritis. These are outlined below.
1. Cetylated Fatty Acids Improve Knee Function in Patients with Osteoarthritis;(2)
In this first randomized, double-blind, and placebo controlled clinical study of cetylated fatty acids, patients were enrolled from two clinics in Bangalore, India. The study was designed to determine the benefit of oral cetylated fatty acids (Celadrin, 350 mg per softgel, 2 TID (2100 mg/day)) on knee range of motion and function in patients with osteoarthritis (OA). Knee OA was diagnosed using the American College of Rheumatology guidelines,(10) by the treating physician and confirmed by the clinical investigator. Sixty-four patients with chronic knee OA of 5 to 6 years standing were evaluated at baseline and at 30 and 68 days after consuming either placebo (n = 31) or cetylated fatty acids (n = 33). The trial evaluations included physician assessment, knee range of motion with goniometry [Gr gonia = angle], and the Lequesne Algofunctional Index (LAI). (For information on the LAI, see the Lequesne Algofunctional Index description below)
After 68 days, patients treated with cetylated fatty acids exhibited: - A significant (p < 0.001) increase in knee flexion (range of motion) of 10.1 degrees compared to 1.1 degrees in the patients given placebo. - Celadrin improvements in range of motion occurred in a linear fashion, demonstrating the accumulative nature of cetylated fatty acids intervention. - An LAI response that indicated a significant (p < 0.001) shift towards functional improvement (-5.0 from the total score for day-30 and -5.4 for day-68), compared to a modest improvement in the placebo group (-2.1 for day-68). The initial LAI total score categorized both treatment groups as having extremely severe osteoarthritis (LAI > 14; Max = 24)
The researchers made the following observations: - The salient feature of this study is that patients treated with cetylated fatty acids achieved appreciable increases in knee range of motion (10.1 degrees) that were above the detectable level determined by statistical power analysis. - When the cetylated fatty acids are compared to NSAID treatment the out come data are equivalent. - Deal et al found that naproxen and diflunisal achieved an improvement in knee flexion of 7.5 degrees in 12 weeks.(11) - Dick et al found that etodolac and piroxicam achieved an improvement in knee flexion of 6.0 to 7.7 degrees.(12) - Busquier et al found that aceclofenac and piroxicam achieved 12.4 and 8.1 degrees respectively over 2 months.(13) - Busquier et al also found in 2 months that aceclofenac produced an LAI reduction of 4.6 points and piroxicam produced an LAI reduction of 5.0 points.(13) - Herrmann et al reported that diclofenac and oxaceprol produced decreases in the LAI after 21 days of 2.8 and 2.5 respectively.(14) - Cetylated fatty acids are effective in improving the symptoms of OA and therefore should be considered as a viable option for treatment for OA.
Description of the Lequesne Algofunctional Index(2)
The Lequesne Algofunctional Index (LAI) has been used extensively in European osteoarthritis studies since 1980. The LAI is a questionnaire with four sections comprised of ten questions and 24 grading points. Section one grades pain and discomfort (8 points), section two grades walking distant (8 points), section three grades physical activity (8 points), and section 4 is the total of all preceding sectional scores. Patients are asked to respond on a 5-point Likert scale (0, 0.5, 1.0, 1.5, and 2.0). Zero is without difficulty and 2 is with difficulty or discomfort. The following questions are from the LAI questionnaire.
SECTION 1: Pain or Discomfort 1. During nocturnal bed rest:
None or insignificant Only on movement or in certain positions With no movements
2. Morning stiffness or regression pain after rising
1 minute or less More than 1 minute but less than 15 minutes 15 minutes or more
3. After standing for 30 minutes 4. While ambulating
None Only after ambulation some distance Early after initial ambulation, increasingly with continued ambulation After initial ambulation, not increasingly
5. While getting up from sitting without help of the arms
SECTION 2: Walking Distance 6. Maximum distance walked (may walk with pain)
Unlimited More than 1 Km, but limited About 1 Km (.63 miles) in about 15 minutes From 500 to 900 meters in about 8 to 15 minutes From 300 to 500 meters From 100 to 300 meters Less than 100 meters With 1 walking stick With 2 walking sticks or crutches
SECTION 3: Physical Activity 7. Able to climb up a standard flight of stairs 8. Able to climb down a standard flight of stairs 9. Able to squat or bend on the knees 10. Able to walk on uneven ground
SECTION 4: Total Score _____
2. Effect of a Cetylated Fatty Acid Topical Cream on Functional Mobility and Quality of Life of Patients with Osteoarthritis;(3)
This study was designed to examine the effect of a topical cream consisting of cetylated fatty acids on knee range of motion and functional performance, in patients diagnosed with osteoarthritis (OA) of one or both knees. Forty patients diagnosed with knee OA were randomly assigned to either topical treatment with cetylated fatty acids (n = 20; age 62.7 +/- 11.7 yrs), or with a suitable placebo topical preparation (n = 20; age 64.6 +/- 10.5 yrs). Patients were evaluated on 3 occasions: at baseline (T1), at 30 min after initial treatment (T2), and after 30 days of treatment with applications being made twice per day (T3). Assessments included knee range of motion, and four functional performance assessments, timed "up-and-go" from a chair, stair climbing, medial step-down test, and the unilateral anterior reach [a performance that involves eccentric flexing of a support leg, while maintaining body weight stability (balance) when extending the other leg a greater distance]. The unilateral anterior reach and medial step-down tests were included because of their reliance on balance, strength, and endurance during performance.
The results are indicated below:
Supine range of motion the knees increased at 30 minutes (T2) and 30 days (T3) in the cetylated fatty acids treated group, whereas no difference was observed in the placebo group.
For stair climbing ability and the up-and-go test (rising from a chair and walking away), significant decreases in the required time to perform were observed at T2 and T3 compared to baseline values (T1) in the cetylated fatty acids group only.
For the medial step-down test, significant improvement was observed at T2 and T3 compared to T1 in cetylated fatty acids group.
For the unilateral anterior reach, significant improvement was observed for both legs in cetylated fatty acids group, and in only the left leg in the placebo group. However, the improvements observed in cetylated fatty acids group were significantly greater than placebo group for both legs.
The researchers concluded that using cetylated fatty acids in a topical application is an effective treatment for improving knee range of motion, and for improving the abilities to ascend and descend stairs, to rise from sitting, to walk, and for improving balance, strength and endurance in patients with knee osteoarthritis.
A unique finding was an immediate effect of the cetylated fatty acids 30 minutes after the initial application.
3. Acetylated Fatty Acid Topical Cream with Menthol Reduces Pain and Improves Functional Performance in Individuals with Arthritis; (4
) This study was done under the auspices of the Human Performance Laboratory, Department of Kinesiology, University of Connecticut, in Storrs, Connecticut. It is an extension study of the preceding study (#2). The researchers wanted to verify that the addition of menthol to cetylated fatty acids topical cream would not compromise its previously demonstrated benefits in osteoarthritis. A single treatment group was used, with a pre-post experimental design to examine the percent of any treatment changes. Individuals diagnosed with osteoarthritis of the knee (N = 10; age, 66.4 +/- 11.5 years) and severe pain (e.g., osteoarthritis, rheumatoid arthritis) of the elbow (N = 8; age, 59.1 +/- 18.2 years) and wrist (N = 10; age, 60.3 +/- 16.8 years) were tested for pain and functional performance before and after 1 week of treatment with a topical cream consisting of cetylated fatty acids and menthol, which was applied twice per day.
After 7days of treatment, in individuals with knee OA, significant improvements in stair-climbing ability (about 12%), "up-and-go" performance (about 12%), balance and strength (about 16.5%), and range of motion (about 3.5%) were observed, as were reductions in pain.
In individuals with severe pain of the wrist and elbow, significant improvements in dynamic (about 24.5 and 22%, respectively) and isometric (about 42 and 33%, respectively) local muscular endurance were observed, as was a reduction in pain. Either group did not demonstrate significant changes in maximal grip strength or maximal force production. A treatment for one week with a topical cream consisting of cetylated fatty acids and menthol was similarly effective for reducing pain and improving functional performance in individuals with arthritis of the knee, wrist and elbow.
The researchers concluded that the percent changes after 7 days of treatment in functional performances were consistent with the prior work on cetylated fatty acids without menthol. The study data from this study further support the use of a topical cream consisting of cetylated fatty acids (with or without menthol) for enhancing the potential for exercise training in this osteoarthritic population. They further noted that this study demonstrated significant improvements in dynamic and isometric local muscular endurance and a reduction in pain in individuals with severe pain in the elbow and wrist.
4. Effects of Treatment with a Cetylated fatty Acid Topical Cream on Static Postural Stability and Plantar Pressure Distribution in Patients with Knee Osteoarthritis;(5)
This study was also performed under the auspices of the Human Performance Laboratory, Department of Kinesiology, University of Connecticut, Storrs, Connecticut. The purpose of this study was to examine the effects of a 30 days treatment with a topical cream consisting of cetylated fatty acids on static postural stability and plantar pressures in patients with osteoarthritis of one or both knees. Forty patients diagnosed with knee OA were randomly assigned to either topical cetylated fatty acid (N = 20; age = 62.7 +/- 11.7 years) or to a suitable placebo topical cream (N = 20; age = 64.6 +/- 10.5 years). Patients were tested on 2 occasions: (a) baseline (T1), and (b) following a 30 days treatment consisting of cream application twice per day (T2). Assessments included 20 and 40 second quiet standing protocols on a force plate to measure center of pressure total excursion length, center of presure velocity, and forefoot and rearfoot plantar pressure distribution.
The following observations were made:
In the cetylated fatty acids treated group, a significant reduction in the COP excursion length and velocity were observed at the end of 30 days (T2), whereas no significant differences were observed in the placebo group.
At T2, in either group, no significant differences have been observed in mean forefoot, rearfoot, or rearfoot-to-forefoot plantar pressure ratios.
Nevertheless, in a subgroup of participants designated to be left or right-side dominant, improvements in the right to left forefoot plantar pressure ratios were observed in both groups.
The researchers concluded that the data indicate that 30 days of treatment with a topical cream of cetylated fatty acids improves static postural stability in patients with knee OA, presumably due to pain relief during quiet standing. They further noted that treatment with cetylated fatty acids may help improve the exercise trainability of people with osteoarthritis.
Rationale for Dosage
The oral study published in the Journal of Rheumatology under reference 2 reflected a Celadrin dosage of 2100 mg per day. This high dose level was selected by the researchers, believing that it was necessary for demonstrating significant improvement over and above the existing arthritic medications that the patients were on throughout the study. Because Celadrin benefits are accumulative, and because dosage compliance is critical to success, the webber natural recommended daily amount is 1400 mg, or 2 X 350 mg softgels, BID.
Celadrin has been shown to be well absorbed into the blood at essentially 95 percent.8 It might be possible to say that the effective oral dosage level can theoretically be low as 150 mg per day, but topically treating the osteoarthritic body at large would require a much longer time to accumulate effective tissue levels of ester. Imagenetix, the developer of Celadrin, takes the conservative position that daily oral amounts should be 1500 mg. The webber naturals recommendation of 1400 mg per day is close enough and supports use compliance.
Proposed Mechanisms of Action for Celadrin
Celadrin clearly demonstrates empirical clinical benefits in managing osteoarthritis after continuous use for 7 to 30 days. However, it is not mechanistically clear how Celadrin works. Cetylated fatty acids are thought to accumulate in cell membranes and induce changes that positively modulate the inflammatory response that is otherwise innate to cells. Four mechanisms have been listed by the developers of Celadrin to infer that cetylated fatty acids function like the anti-inflammatory effects of non-cetylated fatty acids such as monounsaturated fatty acids and EPA, but with greater speed and noticeable greater efficacy. This ability to deliver a greater anti-inflammatory effect compared to noncetylated fatty acids implies the ester structure has pharmacological importance. The following four proposed pathway descriptions of how fatty acids modulate inflammation, and the supporting references, are largely from the scientific literature provided by Imagenetix, Inc.
Reduction in tissue responsiveness to inflammatory cytokines
Monounsaturated fatty acids similar to those found in Celadrin have been shown to inhibit vascular endothelial activation and to reduce tissue responsiveness to inflammatory cytokines. It has been proven that fatty acids regulate a variety of enzymatic processes that also regulate chronic inflammatory disease. Cetylated monounsaturated fatty acids found in Celadrin are inferred to exhibit this ability, but more profoundly.(15-19)
Inhibition of the arachidonic acid cascade
Arachidonic acid is one of the primary mediators of inflammation. Fatty acids from fish oil have been shown to decrease the amount of arachidonic acid in cell membranes, reducing eicosanoid production by cyclooxygenase and lipoxygenase of pro-inflammatory leukotrienes and prostaglandins. Cetylated fatty acids in Celadrin are inferred to work to inhibit eicosanoid production, reducing the arachidonic acid inflammatory cascade.(20-23)
Cellular regulation and communication
There is new and compelling evidence showing that fatty acids have profound impact on cellular regulation and communication.(24) The primary intra-cellular sites for regulation and communication are the endoplasmic reticulum (ER) and the Golgi body apparatus. These two cellular structures are the main synthesizers of the cellular signals. While direct evidence for Celadrin regarding this pathway category is not presently available, the developers of Celadrin believe that the seemingly immediate benefit experience when using the topical cream can only be explained by such rapid cellular communication and regulation of inflammation.
One area that has great potential is the interplay between Celadrin and sphingolipids. Sphingolipids are essential for cellular function and are uniquely integrated with the ER and Golgi body structures. Sphingolipids are considered dynamic regulators of cellular processes. It is the variable structure of sphingolipids and glycerolipids that trigger the formation of microdomains or "rafts" within membranes. Sphingolipids are normally based on an 18-carbon fatty acid backbone, but over 60 different species have been described with chain lengths varying from 14 to 20 carbons differing in saturation and hydroxylation.
The influence of dietary manipulation of these membrane components have been shown in vitro. Yao et al demonstrated that steric acid and EPA could alter the ER and Golgi body lipid trafficking compared to oleic acid.(25) One result was an inhibition of ER lipid synthesis and transfer of membrane lipids to luminal particles. In addition, it was recently demonstrated that the polyunsaturated fatty acid mediation of T-cell inhibition was attributable to signal protein displacement in membranes.(26) It was the alteration in lipid rafts that was identified as the primary loci. The authors concluded that the altered lipid raft membrane distribution could also underlie the clinically apparent immunosuppressive action of polyunsaturated fatty acids in patients with inflammatory disease.
The adipocytokine pathway
One possible pathway that has some intrigue is the recently identified adipocytokine pathway. The primary regulatory agent in this pathway is leptin. Leptin is thought to be involved in the inflammatory process both as an initiator and as a down regulator. As well, leptin has been shown to be induced by other pro-inflammatory mediators such as TNF and interleukin-13 (IL-13). The Celadrin radiolabel distribution experiments demonstrated that the label was incorporated in the triacylglycerol (triglyceride) fraction,8 a prime storage for leptin control.(27,28)
Apart from these four proposed anti-inflammatory pathways, Celadrin is also thought to possess surfactant activity.
Waxes, which are comprised of esters of long chain fatty acids and long chain alcohols, like cetyl alcohol, are recognized for their lubricating quality. A surfactant activity at the membrane level can be expected to impart lubrication to joints and muscles, as well as impart a softening of tissues and increase pliability. The clinically observed accumulative enhancements in joint mobility and flexibility are attributed to a surface activity for Celadrin.
REFERENCES
1. Jellin, J.M., et al, Pharmacist's Letter/Prescriber's Letter Natural Medicines Comprehensive Database, 6th ed., Stockton, CA: Therapeutic Research Faculty, 2006 2. Hesslink., R. Jr, Armstrong, D. 3rd, Nagendran, M.V., et al, Cetylated fatty acids improve knee function in patients with osteoarthritis, J Rheumatol, 29:1708-12, 2002 3. Kraemer, W.J., Ratamess, N.A., Anderson, J.M., et al, Effect of a cetylated fatty acid topical cream on functional mobility and quality of life of patients with osteoarthritis, J Rheumatol, 31:767-74, 2004 4. Kraemer, W.J., Ratamess, N.A., Maresh, C.M., et al, A cetylated fatty acid topical cream with menthol reduces pain and improves functional performance in individuals with arthritis, J Strength Cond Res, 19:475-80, 2005. 5. Kraemer, W.J., Ratamess, N.A., Maresh, C.M., et al, Effects of treatment with a cetylated fatty acid topical cream on static postural stability and plantar pressure distribution in patients with knee osteoarthritis, J Strength Cond Res, 19:115-21, 2005 6. Mastbergen, S.C., et al, Differential direct effects of cyclo-oxygenase-1/2 inhibition on proteoglycan turnover of human osteoarthritic cartilage: an in vitro study, Arthritis Res & Ther, Nov 9; 2005, Available on line http://arthritis-research.com/content/8/1/R2 7. Diehl, H.W., May, E.L., Cetyl myristoleate isolated from Swiss albino mice: an apparent protective agent against adjuvant arthritis in rats, J Pharm Sci, Mar, 83(3):296-299, 1994 8. Distribution of Cetylated Fatty Acids in Rats After Oral or Topical Administration: A Report to Imagenetix, Inc, October 31, 2002, Daniel D. Gallaher, PhD., Professor, Dept of Food Science and Nutrition, University of Minnesota, St Paul MN; Last cited August 10/2006, www.celadrin.com/studies/studies.html 9. Topp, R., et al, Predictors of four functional tasks in patients with osteoarthritis of the knee, Orthop Nurs, 19:49-58, 2000 10. Hochberg, M.C., et al, Guidelines for the medical management of osteoarthritis: II. Osteoarthritis of the knee, Arthritis Rheum, 38:1541-1546, 1995 11. Deal, C.L., et al, Efficacy of diflunisal versus naproxen in osteoarthritis of the knee: an open study, Clin Ther, 9: Suppl C:1-14, 1986 12. Dick, W.C., et al, Safety and efficacy of etodolac compared with piroxicam in patients with degenerative joint disease of the knee, Clin Ther 14:517-526, 1992 13. Busquier, M.P., et al, Comparison of aceclofenac with piroxicam in the treatment of osteoarthritis, Clin Rheumatol, 16:154-159, 1997 14. Herrmann, G., et al, Oxaceprol is a well-tolerated therapy for osteoarthritis with efficacy equivalent to diclofenac, Clin Rheumatol, 19:99-104, 2000 15. Calder, P.C., et al, Fatty acids and lymphocyte functions, Br J Nutri, 87(1):S31-S48, 2002 16. Mata, P., et al, Effect of dietary fat saturation on LDL oxidation and monocyte adhesion to human endothelial cells in vitro, Arterioscler Thromb Vasc Biol, 16:1347-1355, 1996 17. Perez-Jimenez, F., et al, Circulating levels of endothelial function modulated by dietary monounsaturated fat, Atherosclerosis, 145:351-358, 1999 18. Vicennati, V., et al, Hormonal regulation of interleukin-6 production in human adipocytes, Int J Obes Relat Metab Disord, 26(7):905-911, 2002 19. Zaloga, G.P., Marik, P., Lipid modulation and systemic inflammation, Crit Care Clin, 17(1):201-217, 2001 20. Bandeira-Mel, C., et al, The cellular biology of eosinophil eicosanoid formation and function, J Allergy Clin Immunol, 109(3):393-400, 2002 21. Calder, P.C., Grible, R.F., Polyunsaturated fatty acids, inflammation and immunity, Eur J Clin Nutr, 56(3):S14-S19, 2002 22. Fabre, J.L., et al, Transcellular biosynthesis contributes to the production of leukotrienes during inflammatory responses in vivo, J Clin Invest, 109(10): 1373-1380, 2002 23. Kroetz, D.L., Zeldin, D.C., Cytochrome P450 pathways of arachidonic acid metabolism, Curr Opin Lipidol, 13(3): 273-283, 2002 24. Holthuis, J.C., et al, The organizing potential of sphingolipids in intracellular membrane transport, Physiological Reviews, 81(4): 1689-1723, 2001 25. Yao, Y., et al, Regulation of triacylglycerol and phospholipid trafficking by fatty acids in new born swine enterocytes, Am J Physiol Gastrointest Liver Physiol, May, 282:G817-824, 2002 26. Zeyda, M., et al LAT displacement from lipid rafts as molecular mechanism for inhibition of T cell signaling by polyunsaturated fatty acids, J Biol Chem, August 9; 277(32):28418-23, 2002 27. Goldfine, H., From unsaturated fatty acids t6o lipid polymorphism, Biochem Biophys Res Commun, 292(5):1201-1207, 2002 28. Hultgren, Olof H., Tarkowski, A., Leptin in septic arthritis: decreased levels during infection and amelioration of disease activity upon its administration, Arthritis Res, 3(6):389-394, 2001
These statements have not been evaluated by the Food and Drug Administration (FDA). Products are intended to support general well being and are not intended to treat, diagnose, mitigate, prevent, or cure any condition or disease. If conditions persist, please seek advice from your medical doctor. The essence of the current American rule on Traditional Uses is, as stated by FTC, "Claims based on historical or traditional use should be substantiated by confirming scientific evidence, or should be presented in such a way that consumers understand that the sole basis for the claim is a history of use of the product for a particular purpose."
