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Monograph: Conjugated Linoleic Acid

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This monograph is intended to serve as a guide to industry for the preparation of Product Licence Applications (PLA) and labels for natural health product market authorization. It is not intended to be a comprehensive review of the medicinal ingredient. It is a referenced document to be used as a labelling standard. Note: (i) Text in parentheses is additional optional information which can be included on the PLA and product label at the applicant's discretion. The solidus (/) indicates that the terms are synonyms or that the statements are synonymous. Either term or statement may be selected by the applicant. (ii) There is insufficient evidence to support the use of Conjugated linoleic acid (CLA) as a weight loss aid. Consumers wishing to achieve weight loss should consult a health care practitioner prior to taking CLA. (iii) The use of the term "may" in the use or purpose statements reflects the uncertainty of the evidence. For example, some reviews have concluded that CLA does not significantly affect body fat mass. (iv) The claim "May help to support a modest improvement to body composition" refers to evidence showing that CLA may modestly reduce body fat. Weak evidence also demonstrates that CLA may help to modestly increase lean muscle mass. (v) The recommendations for decreased caloric intake and increased physical activity are included as components of the use or purpose statements in order to provide a health context. (vi) Though CLA has been administered to subjects for up to two years, there is insufficient evidence to support any benefits beyond 6 months. As such, a duration of use of 6 months has been included on the monograph. (vii) CLA does not exert positive effects on any health risk biomarkers (e.g. LDL-cholesterol, HDL-cholesterol, plasma glucose, plasma insulin, etc.) and there is some evidence to suggest that its use may be unsafe in particular subpopulations. As such, mandatory risk information is required on the PLA and label to identify subpopulations at risk.

Date: 2010-02-25

NHPID Name

Conjugated linoleic acid (USNLM 2007)

Proper Name(s)

Conjugated linoleic acid ( Pariza 2004 , Pariza et al. 2001 )

Common Name(s)

Source Material

Synthetic (Zajac et al. 2003, Gennaro 2000)
In the triacylglycerol form and the free fatty acid form, CLA is derived from processed safflower or sunflower oil.

Route Of Administration

Oral

Dosage Form(s)

  • The acceptable pharmaceutical dosage forms include, but are not limited to capsules, chewables (e.g. gummies, tablets), liquids, powders, strips or tablets.
  • This monograph is not intended to include foods or food-like dosage forms such as bars, chewing gums or beverages.

Use(s) or Purpose(s)

Statement(s) to the effect of:

Dose(s)

Adults:

Dose(s): 3 - 5 Grams per day

  • Additional information not to be submitted with the compendial PLA (although the quantity of CLA-rich oil may be requested at the NHPD's discretion): Approximately 4-6.5 g CLA-rich oil provides 3-5 g CLA. See the information in the Specifications section for detailed information on the required proportions of the c9t11 and t10c12 CLA isomers.
  • The following directions of use is optional: Take with food. (Watras et al. 2007; Kamphuis et al. 2003)

Duration of use

Consult a health care practitioner for use beyond 6 months  (Watras et al. 2007, Gaullier et al. 2005, Gaullier et al. 2004)

Risk Information

Statement(s) to the effect of:

Caution(s) and Warning(s):

Contraindication(s):
Do not use if you have CVD, diabetes, metabolic syndrome or insulin resistance.  (Tholstrup et al. 2008, Gaullier et al. 2007, Steck et al. 2007, Larsen et al. 2006, Taylor et al. 2006, Gaullier et al. 2005, Smedman et al. 2005, Gaullier et al. 2004, Moloney et al. 2004, Basu et al. 2000a, Basu et al. 2000b)

Known Adverse Reaction(s):
Some people may experience gastrointestinal upset.  (Gaullier et al. 2007, Pinkoski et al. 2006, Berven et al. 2000, Blankson et collab 2000)

Non-medicinal ingredients

Must be chosen from the current Natural Health Products Ingredients Database and must meet the limitations outlined in the database.

Specifications

  • The finished product specifications must be established in accordance with the requirements described in the NHPD Quality of Natural Health Products Guide.
  • The medicinal ingredient must comply with the requirements outlined in the Natural Health Products Ingredient Database (NHPID).
  • The CLA-rich oil must comply with the following chemical specifications: (i) CLA total - greater than 78%, (ii) CLA (c9t11 + t10,c12 isomers) - greater than 74%, (iii) CLA c9,t11 isomers - greater than 36%, (iv) CLA t10,c12 isomers - greater than 36%, (v) CLA trans, trans - less than 3%
  • The maximum peroxide value derived from CLA-rich oil must be less or equal to 1 meq O2/kg and be in accordance with the methods set out by the American Oil Chemists' Society (AOCS) and/or Pharmacopoeial analytical methods. This specification is necessary to ensure the oxidative stability of the CLA (FDA 2007).

References cited

  • Basu S, Risérus U, Turpeinen A, Vessby B. 2000a. Conjugated linoleic acid induces lipid peroxidation in men with abdominal obesity. Clinical Science 99(6):511-516.
  • Basu S, Smedman A, Vessby B. 2000b. Conjugated linoleic acid induces lipid peroxidation in humans. FEBS Letters 468(1):33-36.
  • Berven G, Bye A, Hals O, Blankson H, Fagertun H, Thom E, Wadstein J, Gudmundsen O. 2000. Safety of conjugated linoleic acid (CLA) in overweight and obese human volunteers. European Journal of Lipid Science and Technology 102(7):455-462.
  • Blankson H, Stakkestad JA, Fagertun H, Thom E, Wadstein J, Gudmundsen O. 2000. Conjugated linoleic acid reduces body fat mass in overweight and obese humans. The Journal of Nutrition 130(12):2943-2948.
  • FDA 2007: United States Food and Drug Administration. Guidance for Industry Developing Products for Weight Management Draft Guidance [online]. Washington (DC): United States Department of Health and Human Services, U.S. Food and Drug Administration. [Accessed 2009 October 28]. Available from: http://www.fda.gov/downloads/Drugs/GuidanceComplianceRegulatoryInformation/Guidances/ucm071612.pdf
  • Gaullier JM, Halse J, Hoye K, Kristiansen K, Fagertun H, Vik H, Gudmundsen O. 2004. Conjugated linoleic acid supplementation for 1 y reduces body fat mass in healthy overweight humans. The American Journal of Clinical Nutrition 79:1118-1125.
  • Gaullier JM, Halse J, Hoye K, Kristiansen K, Fagertun H, Vik H, Gudmundsen O. 2005. Supplementation with conjugated linoleic acid for 24 months is well tolerated by and reduces body fat mass in healthy, overweight humans. The Journal of Nutrition 135(4):778-784.
  • Gaullier JM, Halse J, Høivik HO, Høye K, Syvertsen C, Nurminiemi M, Hassfeld C, Einerhand A, O'Shea M, Gudmundsen O. 2007. Six months supplementation with conjugated linoleic acid induces regional-specific fat mass decreases in overweight and obese. British Journal of Nutrition 97(3):550-560.
  • Kamphuis MM, Lejeune MP, Saris WH, Westerterp-Plantenga MS. 2003. The effect of conjugated linoleic acid supplementation after weight loss on body weight regain, body composition, and resting metabolic rate in overweight subjects. International Journal of Obesity and Related Metabolic Disorders 27(7):840-847.
  • Larsen TM, Toubro S, Gundmensen O, Astrup A. 2006. Conjugated linoleic acid supplementation for 1 y does not prevent weight or body fat gain. The American Journal of Clinical Nutrition 83(3):606-612.
  • Pariza MW, Park Y, Cook ME. 2001. The biologically active isomers of conjugated linoleic acid. Progress in Lipid Research 40(4):283-298.
  • Pariza MW. 2004. Perspective on the safety and effectiveness of conjugated linoleic acid. The American Journal of Clinical Nutrition 79(Supplement 6):1132S-1136S.
  • Pinkoski C, Chilibeck PD, Candow DG, Esliger D, Ewaschuk JB, Facci M, Farthing JP, Zello GA. 2006. The effects of conjugated linoleic acid supplementation during resistance training. Medicine and Science in Sports and Exercise 38(2):339-348.
  • Raff M, Tholstrup T, Toubro S, Bruun JM, Lund P, Straarup EM, Christensen R, Sandberg MB, Mandrup S. 2009. Conjugated linoleic acids reduce body fat in healthy postmenopausal women. The Journal of Nutrition 39(7):1347-1352
  • Smedman A, Basu S, Jovinge S, Fredrikson GN, Vessby B. 2005. Conjugated linoleic acid increased C-reactive protein in human subjects. British Journal of Nutrition 94(5):791-795.
  • Steck SE, Chalecki AM, Miller P, Conway J, Austin GL, Hardin JW, Albright CD, Thuillier P. 2007. Conjugated linoleic acid supplementation for twelve weeks increases lean body mass in obese humans. The Journal of Nutrition 137(5):1188-1193.
  • Taylor JS, Williams SR, Rhys R, James P, Frenneaux MP. 2006. Conjugated linoleic acid impairs endothelial function. Arteriosclerosis, Thrombosis, and Vascular Biology 26(2):307-312.
  • Tholstrup T, Raff M, Straarup EM, Lund P, Basu S, Bruun JM. 2008. An oil mixture with trans-10, cis-12 conjugated linoleic acid increases markers of inflammation and in vivo lipid peroxidation compared with cis-9, trans-11 conjugated linoleic acid in postmenopausal women. The Journal of Nutrition 138(8):1445-1451.
  • Watras AC, Buchholz AC, Close RN, Zhang Z, Schoeller DA. 2007. The role of conjugated linoleic acid in reducing body fat and preventing holiday weight gain. International Journal of Obesity 31(3):481-487

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