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American Journal of Clinical Nutrition, Vol. 70, No. 1, 104A-105, July 1999
© 1999 American Society for Clinical Nutrition


Letters to the Editor

Reply to H-M Cheng and K Sundram

Martijn B Katan, Peter L Zock and Peter van de Bovenkamp

Wageningen Centre for Food Sciences and Division of Human Nutrition and Epidemiology Wageningen University Bomenweg 2 6703 HD Wageningen Netherlands

Magda Hectors

Division of General Internal Medicine University Hospital Nijmegen PO Box 9101 6500 HB Nijmegen Netherlands

Dear Sir:

Chen and Sundram suggest that 7-ketocholesterol, cholesterol epoxide, and other cholesterol oxides represent major components of oxidized LDL, and that circulating autoantibodies to such cholesterol oxides may help to clear oxidized LDL in vivo. Treatment of LDL with oxidizing agents in vitro indeed produces cholesterol oxides (oxysterols). However, the amounts of such cholesterol oxides that circulate in LDL in vivo may have been overestimated in early studies including our own (1) because significant amounts of oxysterols may be formed by cholesterol autoxidation during fractionation of plasma (2, 3). We ourselves attempted to discriminate oxysterols formed in vivo and in vitro by adding deuterated cholesterol (m + 7) after blood sampling. After subsequent plasma fractionation (4), the concentrations of deuterated cholesterol {alpha}-epoxide, deuterated 7-ß-hydroxycholesterol, and deuterated 7-ketocholesterol were similar to those of the natural cholesterol oxidation products supposedly already present in vivo (47, 17, and 31 nmol deuterated products/L compared with 62, 23, and 31 nmol natural cholesterol oxides/L, respectively) (van de Bovenkamp and Hectors, unpublished observations, 1996).

This confirms that some of the oxysterols found in plasma may be artifacts produced by autooxidation in vitro. We therefore felt that the evidence for a role of circulating cholesterol oxides in human atherosclerosis was too weak to include in our editorial. The importance of the autoantibodies described by Chen and Sundram is even more speculative.

REFERENCES

  1. Stalenhoef AFH, Kleinveld HA, Kosmeijer-Schuil JG, Demacker PNM, Katan MB. In vivo oxidised cholesterol in atherosclerosis. Atherosclerosis 1993;98:113–4 (letter).[Medline]
  2. Babiker A, Diczfalusy U. Transport of side-chain oxidized oxysterols in the human circulation. Biochim Biophys Acta 1998;1392:333–9.[Medline]
  3. Brown AJ, Jessup W. Oxysterols and atherosclerosis. Atherosclerosis 1999;142:1–28.[Medline]
  4. van de Bovenkamp P, Kosmeijer-Schuil JG, Katan MB. Quantification of oxysterols in Dutch foods: egg products and mixed diets. Lipids 1988;23:1079–85.[Medline]




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