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Comparison of Low Fat and Low Carbohydrate Diets on Circulating Fatty Acid Composition and Markers of Inflammation


Abnormal distribution of plasma fatty acids and increased inflammation are prominent features of metabolic syndrome. We tested whether these components of metabolic syndrome, like dyslipidemia and glycemia, are responsive to carbohydrate restriction. Overweight men and women with atherogenic dyslipidemia consumed ad libitum diets very low in carbohydrate (VLCKD) (1504 kcal:%CHO:fat:protein = 12:59:28) or low in fat (LFD) (1478 kcal:%CHO:fat:protein = 56:24:20) for 12 weeks. In comparison to the LFD, the VLCKD resulted in an increased proportion of serum total n-6 PUFA, mainly attributed to a marked increase in arachidonate (20:4n-6), while its biosynthetic metabolic intermediates were decreased. The n-6/n-3 and arachidonic/eicosapentaenoic acid ratio also increased sharply. Total saturated fatty acids and 16:1n-7 were consistently decreased following the VLCKD. Both diets significantly decreased the concentration of several serum inflammatory markers, but there was an overall greater anti-inflammatory effect associated with the VLCKD, as evidenced by greater decreases in TNF-α, IL-6, IL-8, MCP-1, E-selectin, I-CAM, and PAI-1. Increased 20:4n-6 and the ratios of 20:4n-6/20:5n-3 and n-6/n-3 are commonly viewed as pro-inflammatory, but unexpectedly were consistently inversely associated with responses in inflammatory proteins. In summary, a very low carbohydrate diet resulted in profound alterations in fatty acid composition and reduced inflammation compared to a low fat diet.

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Very low carbohydrate ketogenic diet


Low fat diet




Cholesteryl ester


Cardiovascular disease


Recommended daily allowance


Body mass index




Tumor necrosis factor-α


Vascular endothelial growth factor




Epidermal growth factor


Monocyte chemotactic protein-1


Intracellular cellular adhesion molecule-1


Vascular cellular adhesion molecule-I


Nuclear factor-kappa B


C-reactive protein




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This work was supported by the Dr. Robert C. Atkins Foundation.

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Correspondence to Jeff S. Volek.

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Forsythe, C.E., Phinney, S.D., Fernandez, M.L. et al. Comparison of Low Fat and Low Carbohydrate Diets on Circulating Fatty Acid Composition and Markers of Inflammation. Lipids 43, 65–77 (2008).

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  • Arachidonic acid
  • Palmitoleic acid
  • Ketogenic diet
  • Saturated fat
  • Metabolic syndrome