Effect of a high-fat ketogenic diet on plasma levels of lipids, lipoproteins, and apolipoproteins in children

JAMA. 2003 Aug 20;290(7):912-20. doi: 10.1001/jama.290.7.912.


Context: Little prospective long-term information is available on the effect of a ketogenic diet on plasma lipoproteins in children with difficult-to-control seizures.

Objective: To determine the effect in children with intractable seizures of a high-fat ketogenic diet on plasma levels of the major apolipoprotein B (apoB)-containing lipoproteins, low-density lipoprotein (LDL) and very LDL (VLDL); and the major apolipoprotein A-I (apoA-I)-containing lipoprotein, high-density lipoprotein (HDL).

Design, setting, and patients: A 6-month prospective cohort study of 141 children (mean [SD] age, 5.2 [3.8] years for 70 boys and 6.1 [4.4] years for 71 girls) with difficult-to-treat seizures who were hospitalized for initiation of a high-fat ketogenic diet and followed up as outpatients. This cohort constituted a subgroup of the 371 patients accepted into the ketogenic diet program between 1994 and 2001. A subset of the cohort was also studied after 12 (n = 59) and 24 (n = 27) months.

Intervention: A ketogenic diet consisting of a high ratio of fat to carbohydrate and protein combined (4:1 [n = 102], 3.5:1 [n = 7], or 3:1 [n = 32]). After diet initiation, the calories and ratio were adjusted to maintain ideal body weight for height and maximal urinary ketosis for seizure control.

Main outcome measures: Differences at baseline and 6-month follow-up for levels of total, VLDL, LDL, HDL, and non-HDL cholesterol; triglycerides; total apoB; and apoA-I.

Results: At 6 months, the high-fat ketogenic diet significantly increased the mean plasma levels of total (58 mg/dL [1.50 mmol/L]), LDL (50 mg/dL [1.30 mmol/L]), VLDL (8 mg/dL [0.21 mmol/L]), and non-HDL cholesterol (63 mg/dL [1.63 mmol/L]) (P<.001 vs baseline for each); triglycerides (58 mg/dL [0.66 mmol/L]) (P<.001); and total apoB (49 mg/dL) (P<.001). Mean HDL cholesterol decreased significantly (P<.001), although apoA-I increased (4 mg/dL) (P =.23). Significant but less marked changes persisted in children observed after 12 and 24 months.

Conclusions: A high-fat ketogenic diet produced significant increases in the atherogenic apoB-containing lipoproteins and a decrease in the antiatherogenic HDL cholesterol. Further studies are necessary to determine if such a diet adversely affects endothelial vascular function and promotes inflammation and formation of atherosclerotic lesions.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Adolescent
  • Apolipoproteins / blood
  • Child
  • Child, Preschool
  • Diet*
  • Dietary Fats
  • Female
  • Humans
  • Hyperlipidemias / etiology
  • Infant
  • Ketosis / urine
  • Lipids / blood*
  • Lipoproteins / blood
  • Male
  • Prospective Studies
  • Seizures / diet therapy*


  • Apolipoproteins
  • Dietary Fats
  • Lipids
  • Lipoproteins