Welcome to part 1 of my series on the relationship between dietary saturated fat, dietary cholesterol, blood (serum) cholesterol and the risk of cardiovascular disease. This series of posts is an adapted version of a research paper I recently wrote for my Master of Science in Holistic Nutrition program. The purpose of this paper is to review the evidence in support of, and in discord with, the Lipid and Diet Heart Hypothesis. Today’s post will focus on the history of the Lipid and Diet Heart Hypothesis as well as provide some background information of saturated fat, cholesterol and cholesterol/lipid blood transport. The next posts in the series will outline the scientific evidence for and against the 2 noted hypotheses, as well as outlining proper dietary risk factors for cardiovascular disease.
Cholesterol & Diet Heart Hypothesis Introduction
Over the past number of decades there has been much debate about the role that blood (serum) cholesterol levels play in the development of cardiovascular disease and stroke. This is the core core concept of the lipid Hypothesis (1). Simply stated, this hypothesis implies that high serum cholesterol is a key risk factor for cardiovascular disease (1). It was over 100 years ago that this concept was first discovered by Nikolai N. Anitschkow following a study he performed on high cholesterol fed rabbits revealing that only rabbits with high blood cholesterol levels developed cardiovascular diseases (1). However, this concept was not widely accepted until the 1970s and 1980s (1, 2). Although, today there remains confusion as to the specific role serum cholesterol and other serum lipids play in the risk of cardiovascular disease (3).
Another hypothesis related to cardiovascular disease has received arguably more debate over the past number of decades than the Lipid Hypothesis, the Diet Heart Hypothesis. The Diet Heart Hypothesis states that dietary saturated fat and cholesterol raise serum cholesterol levels and thus, in light of the Lipid Hypothesis, increase the risk of heart disease (4, 6). This relationship was first observed in the 1950s, and later popularized by the work of Dr. Ancel Keys and the famous seven countries study from 1970 (4, 5, 6). As with the lipid hypothesis, there remains confusion as to the specific role that dietary saturated fat and cholesterol play in cardiovascular disease even in light of what seems to be a unanimous acceptance of the Diet Heart Hypothesis in the North American medical community (6).
In combination, the Lipid and Diet Heart Hypothesis state the following:
- Elevated serum cholesterol increases the risk of cardiovascular disease
- Dietary saturated fat increases serum cholesterol
- Dietary cholesterol increases serum cholesterol
- Thus, dietary saturated fat and cholesterol increase the risk of cardiovascular disease.
In order for these combined theories to hold true there must be scientific evidence in support of each of the listed points. As noted, these combined hypotheses have been accepted by the North American medical community and used to develop treatment policies and pharmacological therapies to reduce serum cholesterol levels (6). However, in light of contradictory scientific evidence, there is continued debate as to whether these hypotheses hold true.
Definitions: Saturated Fatty Acids and Cholesterol/Lipid Transport
For the purpose of providing background knowledge for understating of the remainder of this series, a general overview of saturated fatty acids, cholesterol, and their physiological utilization in the body is provided along with an outline of serum lipid transport via lipoproteins.
Saturated Fatty Acids
Saturated fat is a type of fatty acid that contains triglycerides with no double bonds between carbon atoms (nutritional sciences, nourishing traditions). This allows the molecules to stack tight to each other, forming a solid fat at room temperature (nutritional sciences, nourishing traditions). Saturated fats have a structure similar to the below image, the only difference from one saturated fat to another is the number of carbon atoms:
Image taken from: http://firstname.lastname@example.org:15/Anatomy_&_Physiology
Because saturated fatty acid molecules can stack tight to one another, they create a chemically stable fat that is resistant to rancidity/oxidation outside and inside the body (nutritional sciences, nourishing tradition, deep nutrition, 7), also called peroxidation. Peroxidation is the degradation of lipids by free radicals, leading to cell damage and systemic inflammation. Therefore, during periods of high oxidative stress (more free radicles) saturated fats will resist peroxidation.
Saturated fats also have a large number of physiological functions including: cellular structure, utilization of calcium, protecting the liver from toxins, enhancing immune system function, proper utilization of essential fatty acids, and providing antimicrobial properties (nourishing transitions). Furthermore, it is suggested that for the proper utilization of calcium for bone health it is estimated that 50% of our dietary fats should be saturated (nourishing transitions)
Cholesterol is simply a type of lipid having a different chemical structure than most other lipids (nutritional sciences). Due to cholesterol’s multi-ring structure it is referred to as a sterol (nutritional sciences) and has the following structure:
Image taken from: http://chemistry.tutorvista.com/biochemistry/cholesterol-structure.html
Cholesterol is a molecule that is essential to life and has the following functions: synthesis of bile acids, maintaining fluidity and stiffness of cellular membranes, synthesis of steroid hormones (needed for reproduction, energy metabolism, immune system function, calcium homeostasis, and electrolyte balance), synthesis of vitamin D, acts as an antioxidant, needed for proper function of serotonin receptors, and required for proper intestinal wall health (nutritional sciences, nourishing traditions). In additional support of the requirement for cholesterol in the human body is the fact that almost every tissue in our body has the ability to synthesize cholesterol on their own (nutritional sciences).
Cholesterol can also be esterified, attached to a fatty acid, or un-esterified, free cholesterol molecule (nutritional sciences, 8). Esterified and free cholesterol play a critical role in the digestion and absorption of dietary cholesterol (8); discussed later in this series.
Cholesterol’s traditional relation to cardiovascular disease mainly pertains to its transport through the body in blood (serum), otherwise known as lipid transport or the lipid cycle. The lipid cycle refers to the way in which dietary lipids (fats) are transported throughout the body once they are absorbed through the intestines; cholesterol is included in this transport cycle (nutritional sciences). Lipids are hydrophobic (do not dissolve in water) and since our blood is water based, the transport of free lipids is not possible in blood. Therefore, lipids must be transported through the blood in complex molecules called a lipoprotein. Lipoproteins contain triglycerides, cholesterols, phospholipids, proteins, and fat soluble vitamins and minerals (nutritional sciences, deep nutrition). Lipoprotein structure ensures that the hydrophilic (dissolves in water) parts of phospholipids face outwards, forming the majority of the molecule’s surface (nutritional sciences), allowing for efficient transport in the blood.
There are a number of different types of lipoproteins classified by their density as measured by the ratio of protein to lipid (Nutritional sciences). A lipoprotein with more protein than fat would have a higher density than that of a lipoprotein with more fat than protein. Lipoproteins are classified under the following major types: Chylomicron, Chylomicron Remnant, Very Low Density Lipoprotein (VLDL), Intermediate Density Lipoprotein (IDL), Low Density Lipoprotein (LDL), and High Density Lipoprotein (HDL) (Nutritional Sciences). Upon absorption, the intestinal cells package triglycerides, cholesterols, phospholipids, proteins, and fat soluble vitamins and minerals into Chylomicrons. Chylomicrons then circulate through the body delivering fats, cholesterol, and vitamins and minerals to cells for physiological functions. As Chylomicrons release triglycerides to cells, they shrink in size and become Chylomicron Remnants which are then taken up by the liver for processing.
The liver packages and releases VLDL into circulation. VLDL also delivers fats, cholesterol, vitamins, and minerals to peripheral cells for physiological functions. As VLDL particles shrink they become IDL particles and finally LDL particles which are taken up by cells and also used for physiological functions such as cellular structure (nutritional sciences). Ultimately, Chylomicrons, VLDL, and IDL particles mainly deliver lipids to cells while LDL particles mainly deliver cholesterol when taken up by cells. This is because LDL particles have a high concentration of cholesterol, due to their low density, in comparison to the other lipoprotein particles.
Interestingly, lipoproteins can also be distinguished based on the type of protein contained on their surface. For instance, HDL particles contain one apoprotein A-I (apoA-I), LDL particles contain one apoprotein B-100 (apoB), and other lipoproteins contain multiple apoproteins (9, 10). Because HDL and LDL only carrier a single molecule of one type of apoprotein, not seen in significant amounts on other lipoproteins, apoA-I can be used to measure HDL particle number and apoB can be sued to measure LDL particle number (9, 10); the significance of which is discussed later in this series.
So there you have it. A basic explanation of the information required to understand the remainder of posts in this series. Part 2 will be a discussion on dietary saturated fat and it’s relation to serum cholesterol and cardiovascular disease risk. Stay tuned.
The Barefoot Golfer
- Keys, A. (1970). Coronary heart disease in seven countries. Circulation, 41(suppl. I):1-195