In part 1 of this series I provided some background information required for the remainder of this series and in part 2 we determined that saturated fat is not associated with negatively elevated blood cholesterol or an increased risk of heart disease; thus, the Diet Heart Hypothesis does not hold true. Today, in part 3, I will discuss if there is a relationship between dietary cholesterol, blood cholesterol numbers, and the risk of heart disease. I will then focus on information regarding the Lipid Hypothesis and what blood cholesterol measures actually predict the risk of heart disease.
Dietary Cholesterol and Serum Cholesterol
The theory that dietary cholesterol raises serum cholesterol and thus, the risk of cardiovascular disease, has been present in the scientific community since 100 years ago (1). However, over the past 100 years quality scientific evidence in support of this theory is lacking. I was only able to locate one study from 1985 (2) supporting this theory in a human population in a cohort of individuals from Honolulu. Remarkably, the remainder of evidence in support of current United States recommendations for cholesterol intake is from high cholesterol feeding of various animals and the fact the dietary cholesterol is normally contained in foods high in saturated fat (3). Unfortunately, it is difficult to extrapolate this to humans (3).
Conversely, there is a vast amount of literature supporting that dietary cholesterol is not associated with significant increases in serum cholesterol or the risk of cardiovascular disease (4-10). Most recent studies indicate that high cholesterol diets may slightly raise serum LDL cholesterol; however, it also raises serum HDL levels, leading to a nil effect on cardiovascular disease risk (4, 10). Not only that, other studies indicate that while high cholesterol diets do not reduce the risk of cardiovascular disease, low cholesterol diets actually increase the risk of other medical conditions such as cancer (8), nervous system development and function (8), and multiple vitamin deficiencies (9).
A suggested mechanism for the lack of evidence tying dietary cholesterol to elevated serum cholesterol levels is our limited ability to absorb dietary cholesterol (11). Dietary cholesterol is esterified, and in order for cholesterol to be absorbed through the intestinal lining it must be un-esterified, or free cholesterol. Humans do have dietary enzymes that perform this action although it is suggested that such digestion is not complete (11). Cholesterol is a major component of bile, which is released into the small intestine to facilitate fatty acid digestion and the biliary cholesterol released into the intestines is in its free form; thus, it is suggested that the majority of cholesterol absorbed through the intestinal lining is in fact from bile and therefore, originating from our own body (11). Notably, there is a certain proportion of the population that can be considered hyperesponders to dietary cholesterol in which it does have an elevating effect on serum LDL concentrations; however, it has been shown that HDL concentration also raise in similar fashion in these individuals, indicating that there may be an overall nil effect on cardiovascular disease risk in light of the protective effects of HDL (10).
Elevated Serum Cholesterol and Cardiovascular Disease Risk
Development of the Lipid Hypothesis also began over 100 years ago (1) and has progressed to an almost unanimous acceptance within the North American medical community such that pharmaceutical intervention is prescribed to treat elevated LDL and total cholesterol levels (12-15). However, in review of the scientific evidence, the picture is not so clear. There is limited evidence in absolute support of this hypothesis across all populations, much evidence in discord with this hypothesis, and further evidence indicating that serum lipid markers do play a role in cardiovascular disease risk although it is more complicated than simply measuring LDL and total cholesterol concentrations. The questions then becomes, even if dietary saturated fat and cholesterol are found to increase LDL and total cholesterol levels, does this actually increase cardiovascular disease risk?
In Support Of
Much of the available evidence in support of high LDL and total cholesterol concentrations raising cardiovascular disease risk date back to the 1980s. Two related studies (13-14) from this period found that lowering LDL and total cholesterol serum concentrations reduced the risk of cardiovascular disease. Another published paper from 1985 (15) was a report from a National Institute of Health conference in which a consensus statement was developed in support of serum cholesterol’s relation to cardiovascular disease risk. This consensus was developed in review of the current scientific evidence at the time. A further study from 1988 by the National Cholesterol Education Program (16) outlined dietary and pharmaceutical interventions to lower LDL and total cholesterol levels in light of a review of the current scientific evidence at the time linking elevated levels of these markers with cardiovascular disease. I was only able to locate one recent met-analysis reviewing 10 cohort studies from Japan (17) which came to the conclusion that elevated total and LDL serum cholesterol concentrations were positively correlated to the risk of cardiovascular disease; however, this result was only observed in middle aged men and women, not elderly populations.
In Discord With
On the contrary, a large body of scientific literature casts doubt upon a simple direct relationship between elevated LDL and total cholesterol and cardiovascular disease as this relationship is not consistently found from one study to another and is also not consistently found in all populations and cohorts. One study (18) from the early 1990s found that total cholesterol levels had been on the rise in Japan, yet cardiovascular and all-cause mortality had decreased. Furthermore, much of the literature on LDL and total cholesterol serum concentrations find that these markers do not consistently predict cardiovascular disease risk across all populations and cohorts (19-22). In addition, high LDL serum concentrations are not always elevated in patients with cardiovascular disease (23, 24), meaning that people with low or normal LDL levels can still develop cardiovascular disease. For the lipid hypothesis, specific to LDL and total serum cholesterol, to hold true, these markers should accurately indicate risk across all population and cohorts; thus, doubt is cast on this theory and the currently used cardiovascular disease cholesterol markers.
Not only are LDL and total cholesterol inconsistent in the prediction of cardiovascular disease risk, low cholesterol levels have been associated with increased risk of all-cause mortality across a number of populations such as the elderly, chronically ill, and men (25-27). Interestingly, one study (25) found that the longer the time frame of low cholesterol from middle age to elderly increased the risk of all-cause mortality.
Alternative Serum Lipid Markers for Cardiovascular Disease Risk
As inconsistencies in LDL and total cholesterol for markers of cardiovascular disease came to light in the scientific literature, investigations into other serum lipid measures in relation to the risk of cardiovascular disease took place. Evidence shows that serum HDL levels are inversely associated with cardiovascular disease, meaning high levels are protective and low levels are a risk factor (28, 29). These insights lead to the discovery that in combination with serum LDL levels, the ratio of total serum cholesterol to HDL cholesterol was a more accurate predictor of cardiovascular disease risk (30). With the concept that LDL cholesterol levels play a complex role in cardiovascular disease, further research lead to the identification of multiple sizes of LDL particles, small dense or large buoyant LDL, and the hypothesis that small dense LDL had a higher relation to cardiovascular disease (23, 24, 31). However, as with total and LDL cholesterol measures, this finding was not consistent (23). As outlined in part 1, each LDL molecule can contain differing amounts of cholesterol which not only affect the size of each LDL particle but also relate to the number of LDL molecules required to carry a given amount of cholesterol. LDL concentration (LDL-C) is a measure of the total amount of cholesterol contained within all the LDL particles combined, which gives no indication of LDL particle size, or more recently discovered, LDL particle number (LDL-P). Most recent literature points to LDL-P, or apoprotein B-100 (apoB), another measure of LDL-P, as the most accurate predictor of cardiovascular disease risk (32-35). The American Diebetic Association has also published a consensus statement indicating that LDL-P and apoB should be given stronger consideration in testing for cardiovascular disease (22). Evidence indicates that LDL-P and LDL-C are discordant in 50 percent of the population (34), meaning that LDL-C and LDL-P may not both be high or low at the same time (32-35). This finding likely contributes to the inconsistency seen in using LDL-C as the only risk predictor. Furthermore, when LDL-C is low and LDL-P is high, the greatest risk of cardiovascular disease is seen (34, 35). Unfortunately, there is evidence that some cholesterol lowering medications lower LDL-C to a greater extent than LDL-P (34); whether this increases cardiovascular disease risk is not known. Additionally, there is evidence that high LDL-C in combination with low LDL-P provides the best protection from cardiovascular disease (34, 35), and would theoretically reduce the risk of all-cause mortality seen in certain cohorts with low total and LDL-C levels.
Another nail in the Diet Heart Hypothesis is that there is little to no evidence indicating that dietary cholesterol has a negative impact on blood cholesterol of the risk of heart disease. Therefore, along with the conclusion of part 2, we can fully consider the Diet Heart Hypothesis as wrong. On the other hand, in light of the above evidence, it appears that the the Lipid Hypothesis still holds truth with the use of LDL-P or apoB instead of LDL-C and total cholesterol.
This leaves the question: If saturated fat and dietary cholesterol don’t cause heart disease, what dietary components do? This question is the focus of the final instalment of this series. So, if you want to find out what to eat to protect your heart, stay tuned…
The Barefoot Golfer
- http://www.ncbi.nlm.nih.gov/pubmed/16596800 –