DLM: Major Dietary Components for LDL-Cholesterol Reduction (2001)

Citation:
 
Study Design:
Class:
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Quality Rating:
Research Purpose:

To summarize the current understanding of the effects of fatty acids on risk of cardiovascular disease (CVD) and cancer, as well as to identify gaps in our knowledge base that need to be addressed.

Inclusion Criteria:

Research findings presented at the American Heart Association conference "Dietary Fatty Acids and Cardiovascular Health-Dietary Recommendations for Fatty Acids: Is There Ample Evidence?" held June 5-6, 2000.

Exclusion Criteria:

Not applicable

Description of Study Protocol:

Evidence from a variety of studies (epidemiological, clinical, and animal) was presented to identify current understanding of the biological effects of fatty acids and the need for additional information about how fatty acids affect the risk of chronic disease, in the context of refining dietary guidelines.

Data Collection Summary:

Not applicable

Description of Actual Data Sample:

Not applicable

Summary of Results:

Epidemiological, Clinical Trial, and Nonhuman Primate Evidence for the Relationship Between Type of Fat and Coronary Disease

  • Classic studies
    • Saturated fatty acids (carbon chain length of C12:0 to C16:0) raise total and LDL cholesterol levels
    • C18:0 and monounsaturated fat (cis C18:1) are neutral when substituted for carbohydrate
    • N-6 polyunsaturated fatty acids lower cholesterol
    • More recent studies have shown that long chain n-3 fatty acids are hypotriglyceridemic and trans fatty acids are hypercholesterolemic.
  • Epidemiological studies
    • Saturated fat intake is associated with increased risk of coronary heart disease
    • Greatest risk reduction is associated with PUFA intake, and to a lesser extent, with monounsaturated fat
    • Both n-6 and n-3 PUFAs are protective
    • Trans fatty acids are strong predictors of increased coronary risk compared with saturated fat or carbohydrates.
  • Clinical trials
    • Diet can prevent fatal and non-fatal cardiovascular events in individuals with CVD (Lyon and Indian Heart studies)
    • Fish and fish oil have been shown to reduce all-cause mortality and cardiovascular death in patients who had MI.
  • Non-human primate studies
    • Monkeys fed monounsaturated fat developed equivalent amounts of coronary artery atherosclerosis as those fed saturated fat
    • LDL cholesterol was similar in monkeys fed polyunsaturated and monounsaturated fat and lower than in animals fed saturated fat
    • There was an enrichment of cholesterol oleate in plasma cholesterol ester of the monkeys fed the diet high in monounsaturated fat
    • Both n-6 and n-3 PUFAs have been shown to confer protection.

Epidemiological and Clinical Trial Evidence for a Relationship Between Type of Fat and Cancer Risk

  • Epidemiological studies
    • Breast cancer
      • Risk unrelated to fat content across a wide range of intake
      • Limited evidence that monounsaturated fats might be associated with reduced risk and that trans fats might be associated with increased risk
      • Findings are weak and should be regarded as preliminary.
    • Prostate cancer has been associated with higher dietary saturated fat which may be due to an effect of saturated fat on circulating testosterone levels
    • Colorectal cancer risk is increased with higher-fat diets which may reflect an association due more to a direct effect of red meats or carcinogens formed with high-temperature cooking of meats with fat.
  • Clinical trials; limited information on cancer endpoints.

Effects of Fatty Acids on insulin Secretion and Action

  • Animal studies
    • The insulinotropic effect of individual fatty acids increases and decreases with chain length and degree of unsaturation, respectively (invitro studies)
      • The type and amount of circulating fatty acids may determine the insulin secretory response
      • Saturated fat raises insulin resistance.
    • Increased dietary fat reduces insulin action and this insulin resistance is associated with the accumulation of triglyceride in muscle and liver
    • High-fat diets composed of fish oil or safflower oil have markedly different effects on insulin action, and these differences may depend on the ability of fatty acids in fish oil to upregulate lipid oxidation in the liver.
  • Human studies
    • Varying the total fat content of the diet does not affect insulin-mediated glucose disposal
    • Specific fatty acids or their derivatives may have roles other than as energy substrates involving regulation of enzyme activity and gene expression.

Effects of Fatty Acids on Hemostatic Factors and Platelet Function

  • The activity of factor VII decreases and the capacity of the endogenous fibrinolytic system increases when a lower fat, higher fiber diet replaces a high-fat diet
  • Hemostatic proteins generally are not affected by changes in the type of dietary fat e.g. saturated, monounsaturated, trans or n-6 polyunsaturated fats
  • Platelets
    • Interpretation of the studies is difficult because different methods have been used to estimate platelet function, inconsistency is assessment of platelet lipid composition, questions regarding the relationship of in vitro assays to in vivo activity, inconsistent composition and duration of dietary manipulations
    • Generally, composition of the platelet membrane appears to reflect the fatty acid composition of the diet
    • Diets rich in n-3 fatty acids appear to cause platelets to aggregate less at a fixed dose of agonist or to require more agonist to aggregate.

Effects of Fatty Acids on Blood Pressure

  • Supplementation with high doses of n-3 PUFAs can reduce blood pressure
    • Large quantities (3 grams per day) are needed to see a minimal effect in non-hypertensive individuals and only very modest effects in hypertensive individuals
    • DHA is more effective than EPA.
  • Short-term changes in consumption of saturated fat or n-6 PUFAs appear to have little effect on blood pressure
  • Some suggestion that a diet rich in monounsaturated fat can lower blood pressure
  • Regular fish consumption may also reduce blood pressure. There is an additive effect with weight loss in reducing blood pressure.

 Fatty Acids and Endothelial Activation

  • Expression of leukocyte adhesion molecules
    • DHA reduces expression of vascular cell adhesion molecule-1
    • Saturated fatty acids had no inhibitory effects
    • Progressive increase in inhibitory activity with fatty acids of the same chain length but increasing in degree of unsaturation.
      • N-3 fatty acids seem to have the greatest inhibitory effect, with n-6 fatty acids being intermediate, followed by monounsaturated fatty acids.
  • Emerging evidence suggests that with increasing fatty acid unsaturation, there is an accompanying increase in inhibition of endothelial activation.

 Areas for Additional Research

  • Studies with cardiovascular endpoints that go beyond the measurement of surrogate markers
  • Long term studies of fatty acids and cancer
  • Roles of specific fatty acids or their derivatives play in the regulation of enzyme activity and gene expression in insulin-responsive tissues
  • Reliable markers of fat and fatty acid intake because of the challenges associated with collecting food consumption data
  • Individual fatty acids and their effects on other risk factors and the development of atherosclerosis.

 

Author Conclusion:
  • Good understanding of the effects of individual fatty acids on lipids and lipoprotein
  • Unsaturated fatty acids lower total and LDL cholesterol levels when substituted for saturated fatty acids
  • Long-chain n-3 fatty acids from fish oil decrease triglyceride levels, favorable affect platelet function, and decrease blood pressure slightly in hypertensive individuals
  • Oleic acid has been shown to decrease post-prandial factor VII activity
  • Epidemiological studies have shown beneficial effects of unsaturated (both mono- and polyunsaturated) fatty acids compared with saturated fat on incidence of heart disease
  • Controlled clinical trials have demonstrated beneficial effects of diets high in n-6 and n-3 fatty acids on coronary heart disease
  • Some evidence to suggest potentially adverse effects of unsaturated fatty acids in that monounsaturated fat has atherogenic effects in monkeys that are comparable to those of saturated fat
  • Based on a large body of evidence, it is apparent that the optimal diet for decreased risk of chronic diseases is one in which saturated fatty acids are decreased and trans fatty acids from manufactured fats are virtually eliminated
  • Because of the growing health benefits recognized for unsaturated fatty acids, it is likely that a mixture of these fatty acids in the diet will confer the greatest health benefits within the context of a diet moderate in fat
  • Given the limited amount of evidence to date on the effect of individual fatty acids, it is not possible to incorporate specific advice on all the points raised into population-wide dietary guidelines.
Funding Source:
Not-for-profit
0
Foundation associated with industry:
Reviewer Comments:

Strictly a narrative review of research findings presented at a conference; no details of the research studies were included.

Quality Criteria Checklist: Review Articles
Relevance Questions
  1. Will the answer if true, have a direct bearing on the health of patients? Yes
  2. Is the outcome or topic something that patients/clients/population groups would care about? Yes
  3. Is the problem addressed in the review one that is relevant to dietetics practice? Yes
  4. Will the information, if true, require a change in practice? Yes
 
Validity Questions
  1. Was the question for the review clearly focused and appropriate? Yes
  2. Was the search strategy used to locate relevant studies comprehensive? Were the databases searched and the search termsused described? No
  3. Were explicit methods used to select studies to include in the review? Were inclusion/exclusion criteria specified andappropriate? Wereselectionmethods unbiased? No
  4. Was there an appraisal of the quality and validity of studies included in the review? Were appraisal methodsspecified,appropriate, andreproducible? No
  5. Were specific treatments/interventions/exposures described? Were treatments similar enough to be combined? No
  6. Was the outcome of interest clearly indicated? Were other potential harms and benefits considered? Yes
  7. Were processes for data abstraction, synthesis, and analysis described? Were they applied consistently acrossstudies and groups? Was thereappropriate use of qualitative and/or quantitative synthesis? Was variation in findings among studies analyzed? Were heterogeneity issued considered? If data from studies were aggregated for meta-analysis, was the procedure described? No
  8. Are the results clearly presented in narrative and/or quantitative terms? If summary statistics are used, are levels ofsignificance and/or confidence intervals included? Yes
  9. Are conclusions supported by results with biases and limitations taken into consideration? Are limitations ofthe review identified anddiscussed? No
  10. Was bias due to the review's funding or sponsorship unlikely? Yes