Dietary Cholesterol

1. Dietary cholesterol has small effect on serum cholesterol compared to saturated fat

2. Feeding studies provide mixed evidence, however meta-analyses point to a lack of major effect

3. Those with very low baseline dietary cholesterol respond more than those with modest baseline cholesterol intake

4. Adding 300-400 mg cholesterol to a cholesterol free diet results in an increase in serum cholesterol, but subsequent addition of more cholesterol has little, if any, effects

Summary:

The idea that dietary cholesterol increases blood cholesterol seems very logical, however the evidence supporting this hypothesis suggests a very weak relationship. Dr. Ancel Keys was one of the first researchers to test this hypothesis, feeding subjects extremely high levels of dietary cholesterol and measuring their blood response. He found almost no effects, despite absurd amounts of dietary cholesterol. Upon further research, Keys accepted that there is some relationship, and created a formula to predict it: blood cholesterol is proportional to the square root of the amount of dietary cholesterol added.

Change in serum cholesterol between 2 diets = 1.5*(Z2 – Z1), where Z is the square root of the cholesterol content of each diet in mg/1000 kcal

According to Keys’ equation above, if someone consuming a 2,000 calorie diet and 1200mg of cholesterol (4x the recommended level), reduced their total dietary cholesterol by 6-fold  to 200 mg a day, their serum cholesterol would drop by 21.75 mg/dl. Going from 300 mg per 1000 calories eaten to 150 mg per 1000 calories eaten would drop serum cholesterol by a mere 3.75 mg.

During the same time, other researchers believed there was a larger relationship. When they fed subjects cholesterol combined with egg yolk, their blood cholesterol increased. When they consumed much higher doses of pure cholesterol, the blood response was less pronounced. Possible explanations for this were increased bioavailability of the cholesterol when mixed with egg yolk, or the possibility that another ingredient besides the yolk’s cholesterol was increasing blood cholesterol levels. However, the amount of egg yolk required to make a significant difference is usually quite large.

Other researchers have since confirmed Ancel Keys’ square root relationship, adding that dietary cholesterol has greatest effects on serum cholesterol if it is added to a low cholesterol, or cholesterol-free diet. At moderate cholesterol intakes, serum cholesterol changed very little with added cholesterol. A 1997 meta-analysis compiled 9 predictive equations since 1990, calculating that for a 2500 kcal diet, a 1.37-2.68 mg/dl decrease in serum cholesterol could be expected for every 100 mg/day decrease in dietary cholesterol. The prediction based on their meta-analysis was a 2.2 mg/dl decrease in serum cholesterol for every 100 mg/day decrease in dietary cholesterol.

The American Heart Association recommends eating less than 300mg of cholesterol per day. This seems somewhat futile given the predictions above, and rather unattainable for the omnivore considering one 6 ounce piece of chicken breast has 168 mg. It also encourages low-protein diets, which seem to be less effective for weight loss and satiety. To decrease blood cholesterol, the research suggests that focus should be placed on replacing saturated fats with polyunsaturated fats. Limiting dietary cholesterol seems to have little benefit.

Bibliography:

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Meta-analyses and reviews
Dietary cholesterol has no effect
Dietary cholesterol effects serum cholesterol

Meta-analyses & Reviews: Effects of dietary cholesterol on serum cholesterol:

Howell et al. 1997. Plasma lipid and lipoprotein responses to dietary fat and cholesterol: a meta-analysis

  • Overview: To test the findings of the past 40 years on the relationship between dietary fat and cholesterol on plasma lipid concentrations. This analysis specifically looked at if the findings of the tightly controlled feeding studies could be generalized to practical dietary interventions
  • Main Points: Data from 224 published studies on 8,143 subjects, including 878 diet-blood lipid comparisons were subjected to weighted multiple regression analysis. Inclusion criteria includes: studies published in English between 1966-1994, reporting data on changes in dietary cholesterol and fat corresponding to changes in serum cholesterol
  • Outcome: Predictions indicate that compliance with current dietary recommendations (30% energy from fat, <10% from saturated fat, and <300 mg cholesterol/day) will reduce plasma total and LDL cholesterol by ~5%, when compared to average american diet
  • For dietary cholesterol specifically: All predictive equations since 1990 suggest a small reduction of serum cholesterol: for a 2500 kcal diet, a 1.37-2.68 mg/dl decrease for every 100 mg/day decrease in dietary cholesterol. Prediction based on this meta-analysis is: 2.2 mg/dl decrease per 100 mg/day decrease in dietary cholesterol.
  • Comments: According to their conclusion, decreasing dietary cholesterol to lower serum cholesterol seems futile. According to the discussion, their results are less dramatic than the NIH would predict: 100 mg increase in dietary cholesterol for a 2500 kcal diet would result in a 10 mg/dL increase in serum cholesterol.

Hopkins, Paul. (1992). Effects of dietary cholesterol on serum cholesterol: a meta-analysis and review

Overview:

  • Mean reported changes in cholesterol from 27 studies in which controlled diets were supplied by a metabolic kitchen provided 76 data points

Main Points/Outcome:

  • Dietary cholesterol has greatest effect on serum cholesterol if it is added to a low cholesterol diet. At moderate cholesterol intakes, serum cholesterol changed very little.
  • If baseline dietary cholesterol was zero, the predicted change in serum cholesterol when given 2500 mg of dietary cholesterol was about 21 mg/dl
  • If baseline dietary cholesterol was 300 mg, the predicted change in serum cholesterol when given 2500 mg of dietary cholesterol was about 3.7 mg/dl
  • If baseline dietary cholesterol was 500 mg, adding 2500 mg of dietary cholesterol had almost no effect

Ancel Keys, et al. 1955. Diet and serum cholesterol in man: lack of effect of dietary cholesterol.

Overview:

  • Report by Ancel Keys on the “dietary experiments on men under completely controled conditions, as well as of both cross-sectional and longitudinal studies on Men in Minnesota and men in Sardinia.”

Outcome:

  • Cross-sectional surveys in Minnesota on young men - no relationship between dietary cholesterol and the total serum cholesterol concentration
  • Two surveys on Island of Sardinia - failed to show any difference in the serum cholesterol concentrations of men of the same age, physical activity, relative body weight, and dietary pattern, but differing markedly in cholesterol intake
  • Careful study during 4 years with 33 men whose diets consistently very low in cholesterol - serum cholesterol values did not differ from 35 men on very high cholesterol diet
  • Comparisons made of 23 men before and after they doubled their cholesterol intake and of 41 men who halved their intake - failed to show any response in serum cholesterol level in 4-12 months
  • Detailed study of the complete dietary intakes of 119 Minnesota businessman - failed to show any significant increase in serum cholesterol with increasing dietary cholesterol intake
  • 4 completely controlled experiments on men - addition or removal of 500-600mg of cholesterol a day had no effect on serum cholesterol
  • Completely controlled experiment on 5 physically active men - changing from a diet of 500 mg cholesterol to 0 mg of cholesterol had no effect on serum cholesterol
  • In completely controlled experiment in 13 men - no significant effect in changing cholesterol from 374 mg/day to 1369 mg/day, or from 1369mg/day to 374 mg/day on serum cholesterol.

Comments:

  • They conclude that “in adult men, the serum cholesterol is essentially independent of the cholesterol intake.”

Feeding studies showing cholesterol has no effect/extremely small effect on blood cholesterol:

Keys et al. 1965. Serum cholesterol response to changes in the diet: II. The effect of cholesterol in the diet.

  • Overview: A series of metabolic ward experiments, with 22 physically healthy men in each, covered dietary cholesterol intakes from 50 to 1450 mg. daily, with all other variables controlled.
  • Main Points: Many studies at this time were done in metabolic wards, allowing the researchers to be be extremely meticulous and complete in controlling for possible confounding variables
  • Outcome: The serum response was the same over a wide range of dietary fat composition. Ordinary American diets ranged from about 150 to 350 mg cholesterol/ 1000 calories consumed. These extremes correspond to average difference of about 9 mg/100 ml of serum. If all other variables constant, change from 250 mg/1000 calories to 0 mg/1000 calories results in a change of 24 mg/100 ml of serum. A 50% decrease in cholesterol results in a 7 mg difference in blood cholesterol.
  • Comments: Researchers summarized, saying to control blood cholesterol “dietary cholesterol should not be completely ignored but attention to this factor alone accomplishes little.”

Messinger et al. 1950. Effect of feeding egg yolk and cholesterol on serum cholesterol levels.

  • Overview: A series of metabolic ward experiments, with 6-10 subjects consuming various levels of cholesterol, and egg yolk powder.
  • Main Points: 4 experiments performed: 6 subjects fed 150 grams egg yolk with 2.5% cholesterol for 48 days; 10 subjects fed similar diet as first group, with a control period of 48 days and a feeding period of 42; 8 patients fed 100 grams of egg yolk powder daily; 5 men given either cholesterol with egg yolk powder, or high levels of pure cholesterol
  • Outcome: Higher blood cholesterol levels were seen when given egg yolk powder and 3.75 grams cholesterol, compared to 15-30 grams of pure cholesterol. All subjects experienced increased blood cholesterol if egg yolk was present
  • Comments: Researchers summarized, saying “there is a substance…in egg yolk which elevates cholesterol level in human serums. The amount necessary to produce this result is well above that in the amount of egg yolk consumed in the ordinary diet.”

Feeding studies showing cholesterol has effects on blood cholesterol:

Mattson et al. 1972. Effect of dietary cholesterol on serum cholesterol in man

  • Overview: 70 male prisoners, ages 21-48, given diets with 4 different cholesterol ranges, while keeping fatty acid composition the same
  • Main Points: All diets had same amount of macronutrients and calories. Added cholesterol obtained from dry egg yolk. Subjects began by eating a cholesterol free diet for 21 days; Range of cholesterol was from 0 mg to 317 mg/1,000 kcal
  • Outcome: When subjects increased dietary cholesterol from 0 mg to 317 mg/1000 kcals, the cholesterol level increased by 25%
  • Comments: Researchers concluded that “a further increase in the intake of cholesterol probably would not have caused a marked increase in serum cholesterol” since other researchers found that further increments of dietary cholesterol have minimal effects

Grande et al. 1965. Effect of dietary cholesterol on man’s serum lipids

  • Overview: Study involving 13 men, looking at the effects on serum lipids of adding 291 mg of cholesterol to diets containing 3mg of cholesterol with different fatty acid composition
  • Main Points: The relationship between dietary cholesterol and serum cholesterol can be predicted mathematically
  • Outcome: Serum cholesterol appears to be a linear function of the square root of the cholesterol in the diet, and predicted by the formula: Change in serum cholesterol = 1.5*(Z2 – Z1), where Z is the square root of the cholesterol content of each diet in mg/1000 kcal
  • Comments: In other words, if someone consuming a 2,000 calorie diet and 1200mg of cholesterol (4x the recommended level) reduced their total dietary cholesterol by 6-fold to 200 mg a day, their serum cholesterol would drop by 21.75 mg/dl. Going from 300 mg / 1000 kcal to 150 mg / 1000 kcal would drop serum cholesterol by 3.75 mg

Connor et al. 1964. The interrelated effects of dietary cholesterol and fat upon human serum lipid levels

  • Overview: 6 men kept in metabolic ward for 16 weeks given different diets differing in fatty acid composition and cholesterol
  • Main Points: The men ate 4 different diets in sequence, each for 4 weeks: cholesterol free; 729mg cholesterol from egg yolk and beef with high saturated fat content; cholesterol free with high polyunsaturated fat content; 725mg cholesterol as egg yolk and beef with high polyunsaturated fat content
  • Outcome: Serum cholesterol decreased by a mean of 38mg/dl when cholesterol completely removed from the diet in presence of high saturated fat intake; Addition of 725 mg to a cholesterol-free diet raised serum cholesterol  by a mean of 28mg/dl
  • Comments: Completely removing dietary cholesterol from diet, and adding high levels of cholesterol to a cholesterol free diet result in changes in serum cholesterol levels that are relatively small considering the size of the changes in dietary cholesterol.

Steiner et al. 1962. Importance of dietary cholesterol in man

  • Overview: 8 patients, were given diets with and without crystalline cholesterol combined with olive oil
  • Outcome: Significant increase in cholesterol occurred in all patients. Mean increase of 26%
  • Comments: Researchers mention the discrepancy of their results with other similar studies. They claim it may be due to the method of administering cholesterol to facilitate absorption

Connor et al. 1961. The serum lipids in men receiving high cholesterol and cholesterol-free diets

  • Overview: 6 men aged 41-52 selected from prison volunteers and hospitalized in a metabolic ward for 13 weeks given various diets identical except for their cholesterol and egg yolk content
  • Main Points: Cholesterol intake ranged from zero during the cholesterol-free periods to a maximum of 1,425 mg when egg yolk was present, and up to 3,600 mg of pure cholesterol when egg yolk not present
  • Outcome: Egg yolk and cholesterol resulted in a mean increase in serum cholesterol of 69mg/100 ml. 475 mg of cholesterol produced a mean increase of 66 mg/100ml of serum cholesterol, while an addition of twice this amount led to no greater serum cholesterol increase; When pure cholesterol was added without egg yolk (up to 3,600 mg), the rise in serum cholesterol was much smaller, about 19mg/100ml
  • Comments: It appears that when egg yolk and cholesterol are added to the diet, serum cholesterol raises a considerable amount. But when 2.5 times as much pure cholesterol are added, without egg yolk, the rise is minimal

Beveridge et al. 1960. The response of man to dietary cholesterol

  • Overview: 93 college students consumed fat free diet, then fed varying amounts of dietary cholesterol
  • Main Points: Cholesterol intake ranged from zero to 1600 mg/950 kcals; 67 subjects completed the study
  • Outcome: Between intakes of 13 – 634 mg of cholesterol per day, serum cholesterol increased sharply; no further increases were obtained at intakes of 1300-4500 mg; After 8 days, subjects given 100 mg/950 kcals had an approximate 10% increase in serum cholesterol; Subjects given 1600 mg/950 kcals had about a 28% increase in serum cholesterol
  • Comments: After eating a fat-free diet, adding cholesterol to the diet increased serum cholesterol, but only up to 1300 mg/950 kcals
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