Cardiovascular Disease and Eating Right: The Facts

The facts on Cardiovascular Disease

This article is going to explore the development of cardiovascular disease. Since the previous iteration of this article, there is a lot of new information that has come to light through the research.

This Scientific Statement by the (American Heart Association) is by far the most sourced and accurate information on the development of cardiovascular disease and atherosclerosis that can lead to heart attacks and strokes.

As the goal is to give you the most accurate and up-to-date information, I’ve decided to go through the entire review and convert it into layman terms so that everyone can understand what they’re talking about. The statement is highly technical, and it’s very easy to misunderstand what they are saying when there is so much misinformation out there on triglycerides, VLDL, LDL, and HDL.

 


Introduction and Scope of the Problem

The AHA recognized in 2011, that there were tons of issues surrounding cardiovascular disease (CVD) and the paradoxes in measuring LDL as an indicator of CVD and atherosclerosis.

A long-standing association exists between elevated triglyceride levels and cardiovascular disease* (CVD).1,2 However, the extent to which triglycerides directly promote CVD or represent a biomarker of risk has been debated for 3 decades.3 To this end, 2 National Institutes of Health consensus conferences evaluated the evidentiary role of triglycerides in cardiovascular risk assessment and provided therapeutic recommendations for hypertriglyceridemic states.4,5 Since 1993, additional insights have been made vis-à-vis the atherogenicity of triglyceride-rich lipoproteins (TRLs; ie, chylomicrons and very low-density lipoproteins), genetic and metabolic regulators of triglyceride metabolism, and classification and treatment of hypertriglyceridemia. It is especially disconcerting that in the United States, mean triglyceride levels have risen since 1976, in concert with the growing epidemic of obesity, insulin resistance (IR), and type 2 diabetes mellitus (T2DM).6,7 In contrast, mean low-density lipoprotein cholesterol (LDL-C) levels have receded.7 Therefore, the purpose of this scientific statement is to update clinicians on the increasingly crucial role of triglycerides in the evaluation and management of CVD risk and highlight approaches aimed at minimizing the adverse public health–related consequences associated with hypertriglyceridemic states. This statement will complement recent American Heart Association scientific statements on childhood and adolescent obesity8 and dietary sugar intake9 by emphasizing effective lifestyle strategies designed to lower triglyceride levels and improve overall cardiometabolic health.

Triglyceride levels seem to be associated with CVD, but LDL levels have been reduced overall. That’s the paradox. Triglyceride and LDL levels were being used to measure risk, but these were not quite accurate as they seemed, at least for LDL levels.

3. Epidemiology of Triglycerides in CVD Risk Assessment
[…]
3.1. Methodological Considerations and Effect Modification

Triglyceride has long been the most problematic lipid measure in the evaluation of cardiovascular risk. First, the distribution is markedly skewed, which necessitates categorical definitions or log transformations. Second, variability is high (Section 10) and increases with the level of triglyceride.12 Third, the strong inverse association with high-density lipoprotein cholesterol (HDL-C) and apolipoprotein (apo) AI, suggests an intricate biological relationship that may not be most suitably represented by the results of multivariate analysis. Finally, evidence from prospective studies of the triglyceride association supports a stronger link with CVD risk in people with lower levels of HDL-C13,14 and LDL-C13,14 and with T2DM.15,16 Such an effect modification could obscure a modest but significant effect, as demonstrated recently.17
[…]
A pivotal consideration is how triglycerides may directly impact the atherosclerotic process in view of epidemiological studies that have failed to demonstrate a strong relationship between very high triglyceride levels and increased CVD death.13,20 As will be described in Section 4, hydrolysis of TRLs (eg, chylomicrons, very low-density lipoproteins [VLDL]) results in atherogenic cholesterol-enriched remnant lipoprotein particles (RLPs). Accordingly, recent evidence suggests that nonfasting triglyceride is strongly correlated with RLPs,21 and in 2 recent studies, nonfasting triglyceride was a superior predictor of incident CVD compared with fasting levels.21,22

Even simply measuring triglyceride levels directly for “high” or “low” does not necessarily indicate cardiovascular disease event — heart attacks and stroke — risk.

You should now be getting a much clearer understanding of why there is a lot of confusion about simply measuring blood lipid levels as serious risk factors. The data indicates there is a correlation between elevated blood lipid levels, but simply measuring the levels of any individual person doesn’t tell us anything about their individual risk of an event like a heart attack or stroke.

3.2. Case-Control Studies, Including Angiographic Studies

Triglyceride has routinely been identified as a “risk factor” in case-control and angiographic studies, even after adjustment for total cholesterol (TC) or LDL-C23,–,34 and HDL-C.24,27,–,29,33,34 In another case-control study, case subjects were 3-fold more likely to exhibit small, dense low-density lipoprotein (LDL) particles, referred to as the “pattern B” phenotype.35 However, the triglyceride level explained most of the risk of the pattern B phenotype and was a stronger covariate than LDL-C, intermediate-density lipoprotein (IDL) cholesterol, or HDL-C. Overall, data from case-control studies have supported triglyceride level as an independent CVD risk factor.

The previous rendition of this article looked at the Pattern B LDL particles (small, dense LDL) as one of the main factors in CVD and atherosclerotic development, but that seems to be mistaken. Hence, the total re-write of this article.

So what is it? I’m going to keep the rest of the 3.x section because I don’t think it’s particularly relevant to understanding the process (just more data from trials). The next section on 4.x is about mechanisms, which is what we are all here for.

Pathophysiology of Hypertriglyceridemia

4. Pathophysiology of Hypertriglyceridemia
4.1. Normal Metabolism of TRLs
4.1.1. Lipoprotein Composition

Lipoproteins are macromolecular complexes that carry various lipids and proteins in plasma.41 Several major classes of lipoproteins have been defined by their physical and chemical characteristics, particularly by their flotation characteristics during ultracentrifugation. However, lipoprotein particles form a continuum, varying in composition, size, density, and function. The lipids are mainly free and esterified cholesterol, triglycerides, and phospholipids. The hydrophobic triglyceride and cholesteryl esters (CEs) compose the core of the lipoproteins, which is covered by a unilamellar surface that contains mainly the amphipathic (both hydrophobic and hydrophilic) phospholipids and smaller amounts of free cholesterol and proteins. Hundreds to thousands of triglyceride and CE molecules are carried in the core of different lipoproteins.

Apolipoproteins are the proteins on the surface of the lipoproteins. They not only participate in solubilizing core lipids but also play critical roles in the regulation of plasma lipid and lipoprotein transport. Apo B100 is required for the secretion of hepatic-derived VLDL, IDL, and LDL. Apo B48 is a truncated form of apo B100 that is required for secretion of chylomicrons from the small intestine.

Back to science class.

Basically, lipoproteins are a normal part of human metabolism as they carry all sorts of various triglycerides (fat) to various parts of the body. This includes cholesterol. These fats are used in normal human metabolism for energy, making cell membranes, repairing damage done to cells, and things of that nature. Apolipoproteins are on the surface of these lipoproteins and basically act as “lock and key” in determining where the various triglycerides go in the body.

4.2. Transport of Dietary Lipids on Apo B48–Containing Lipoproteins

Figure 3 provides an overview of triglyceride metabolism. After ingestion of a meal, dietary fat and cholesterol are absorbed into the cells of the small intestine and are incorporated into the core of nascent chylomicrons. Newly formed chylomicrons, representing 80% to 95% triglyceride as a percentage of composition of lipids,41 are secreted into the lymphatic system and then enter the circulation at the junction of the internal jugular and subclavian veins. In the lymph and blood, chylomicrons acquire apo CII, apo CIII, and apo E. In the capillary beds of adipose tissue and muscle, they bind to glycosylphosphatidylinositol-anchored HDL-binding protein 1 (GPIHBP1),42 and core triglyceride is hydrolyzed by the enzyme lipoprotein lipase (LPL) after activation by apo CII.43 The lipolytic products, free fatty acids (FFAs), can be taken up by fat cells and reincorporated into triglyceride or into muscle cells, where they can be used for energy. In addition to apo CII, other activators of LPL include apo AIV,44 apo AV,45 and lipase maturation factor 1 (LMF1),46 whereas apo CIII47 and angiopoietin-like (ANGPTL) proteins 3 and 448 inhibit LPL. Human mutations in LPL, APOC2, GPIHBP1, ANGPTL3, ANGPTL4, and APOA5 have all been implicated in chylomicronemia (Section 5).

The consequence of triglyceride hydrolysis in chylomicrons is a relatively CE- and apo E–enriched chylomicron remnant (CMR). Under physiological conditions, essentially all CMRs are removed by the liver by binding to the LDL receptor, the LDL receptor–related protein, hepatic triglyceride lipase (HTGL), and cell-surface proteoglycans.49,–,51 Apo AV facilitates hepatic clearance of CMRs through direct interaction with SorLA.52 HTGL also plays a role in remnant removal,49 and HTGL deficiency is associated with reduced RLP clearance. However, studies53 have indicated that HTGL is elevated in T2DM (Section 6) and may be an important contributor to low HDL-C levels in this disease.

Here’s the normal process simplified.

  1. You eat fat and it makes it’s way down through the stomach. The gallbladder releases bile to help absorb the fat.
  2. In the small intestines, it gets absorbed to form chylomicrons which are 80-95% triglycerides.
  3. These are absorbed into the lymphatic system and into the blood stream.
  4. They go all throughout the body where the “apolipoproteins” bind and start the process of release the fats call hydrolyzation.
  5. Once the triglycerides are released into the blood stream — called free fatty acids (FFA) at this point — they can be absorbed into cells directly.
  6. Mutations can occur which mess up this process.

4.3. Transport of Endogenous Lipids on Apo B100–Containing Lipoproteinstrl

4.3.1. Very Low-Density Lipoproteins

VLDL is assembled in the endoplasmic reticulum of hepatocytes. VLDL triglyceride derives from the combination of glycerol with fatty acids that have been taken up from plasma (either as albumin-bound fatty acids or as triglyceride–fatty acids in RLPs as they return to the liver) or newly synthesized in the liver. VLDL cholesterol is either synthesized in the liver from acetate or delivered to the liver by lipoproteins, mainly CMRs. Apo B100 and phospholipids form the surface of VLDL. Although apos CI, CII, CIII, and E are present on nascent VLDL particles as they are secreted from the hepatocyte, the majority of these molecules are probably added to VLDL after their entry into plasma. Regulation of the assembly and secretion of VLDL by the liver is complex; substrates, hormones, and neural signals all play a role. Studies in cultured liver cells51,54 indicate that a significant proportion of newly synthesized apo B100 may be degraded before secretion and that this degradation is inhibited when hepatic lipids are abundant.54

Once in the plasma, VLDL triglyceride is hydrolyzed by LPL, generating smaller and denser VLDL and subsequently IDL. IDL particles are physiologically similar to CMRs, but unlike CMRs, not all are removed by the liver. IDL particles can also undergo further catabolism to become LDL. Some LPL activity appears necessary for normal functioning of the metabolic cascade from VLDL to IDL to LDL. It also appears that apo E, HTGL, and LDL receptors play important roles in this process. Apo B100 is essentially the sole protein on the surface of LDL, and the lifetime of LDL in plasma appears to be determined mainly by the availability of LDL receptors. Overall, ≈70% to 80% of LDL catabolism from plasma occurs via the LDL receptor pathway, whereas the remaining tissue uptake occurs by nonreceptor or alternative-receptor pathways.41,53

4.4. Metabolic Consequences of Hypertriglyceridemia

Hypertriglyceridemia that results from either increased production or decreased catabolism of TRL directly influences LDL and HDL composition and metabolism. For example, the hypertriglyceridemia of IR is a consequence of adipocyte lipolysis that results in FFA flux to the liver and increased VLDL secretion. Higher VLDL triglyceride output activates cholesteryl ester transfer protein, which results in triglyceride enrichment of LDL and HDL (Figure 4). The triglyceride content within these particles is hydrolyzed by HTGL, which results in small, dense LDL and HDL particles. Experimental studies suggest that hypertriglyceridemic HDL may be dysfunctional,55,56 that small, dense LDL particles may be more susceptible to oxidative modification,57,58 and that an increased number of atherogenic particles may adversely influence CVD risk59; however, no clinical outcome trials to date have determined whether normalization of particle composition or reduction of particle number optimizes CVD risk reduction beyond that achieved through LDL-C lowering.

An additional complication in hypertriglyceridemic states is accurate quantification of atherogenic particles in the circulation. That is, a high concentration of circulating atherogenic particles is not reliably assessed simply by measurement of TC and/or LDL-C. Moreover, as triglyceride levels increase, the proportion of triglyceride/CE in VLDL increases (ie, >5:1), which results in an underestimation of LDL-C based on the Friedewald formula.60 Although this scientific statement will address other variables to consider in the hypertriglyceridemic patient (eg, apo B levels), it supports the quantification of non–HDL-C.60,61

Very low density lipoprorteins (VLDL) are made in the liver from from fatty acids. Once they get released into the blood stream, it’s broken down into smaller dense VLDL and IDL (intermediate density lipoproteins). IDL can get further broken down into LDL. Therefore, increases of VLDL is a precursor to smaller dense LDL and HDL particles, of which there is experimental evidence to show that this type of HDL is dysfunctional, small dense LDL can be oxidated, and increase of said particles likely increases atherosclersis risk.

The last paragraph points out the fact that high atherogenic particle circulation is NOT quantified by triglyceride concentrations or LDL-C measurements. Also, triglyceride concentration is not accurately quantified as triglycerides are in VLDL and not able to be measured by just taking blood lipid samples.

Chart from the study showing how VLDL processing works:

View post on imgur.com

4.5. Atherogenicity of TRLs

In human observational studies, TRLs have been associated with measures of coronary atherosclerosis.62 To provide a pathophysiological underpinning for observations that relate specific lipoprotein particles to human atherosclerosis or CVD, experimental models have been developed to investigate the impact of specific lipoprotein fractions on isolated vessel wall cells. For example, in macrophage-based studies, lipoprotein particles that increase sterol delivery or reduce sterol efflux or that promote an inflammatory response are considered atherogenic. In endothelial cell models, lipoprotein particles that promote inflammation, increase the expression of coagulation factors or leukocyte adhesion molecules, or impair responses that produce vasodilation are also considered atherogenic. These experimental systems have been used to understand the mechanisms by which modified LDL particles are associated with atherosclerosis in humans and in animals.

When one evaluates the usefulness of these systems, it is important to recognize that triglyceride overload is not a classic pathological feature of human atherosclerotic lesions, because the end product, FFA, serves as an active energy source for myocytes or as an inactive fuel reserve in adipocytes. However, the by-product of TRLs (ie, RLPs) may lead to foam cell formation63 in a manner analogous to modified LDL. In addition, TRLs share a number of constituents with classic atherogenic LDL particles. They include the presence of apo B and CE. Although TRLs contain much less CE than LDL particles on a per particle basis, there are pathophysiological states (eg, poorly controlled diabetes mellitus [DM]) in which CEs can become enriched in this fraction. TRLs also possess unique constituents that may contribute to atherogenicity. For example, the action of LPL on the triglycerides contained in these particles releases fatty acid, which in microcapillary beds could be associated with pathophysiological responses in macrophages and endothelial cells. Apo CIII contained in TRLs has also been shown to promote proatherogenic responses in macrophages and endothelial cells. In the following paragraphs, we will consider selected aspects of the atherogenicity of TRL using in vitro macrophage and endothelial cell models and associated in vivo correlates.

Since they can’t do studies on humans because of ethics, they basically look at experimental evidence showing increased inflammation, accumulation, and deposition of particles onto the blood vessel wall and decreased removal of said particles to be classified as the mechanisms of “causing atherosclerosis.”

Overall, it is the triglyceride rich lipids (TRLs) with certain receptors like apo B, CE, Apo CIII and such that are pro-inflammatory and therefore most likely the cause of said atherosclerosis. In particular these are summarized by:

  • 4.5.1. Remnant Lipoprotein Particles — after VLDL is made and split up in the blood stream
  • 4.5.2. Apo CIII — major component of circulating TRLs and correlated with increased blood triglyceride levels
  • 4.5.3. Macrophage LPL — increase the expression of inflammatory proteins, adhesion molecules, and coagulation factors in endothelial cells or monocytes and macrophages

5. Causes of Hypertriglyceridemia
5.1. Familial Disorders With High Triglyceride Levels
5.2. Obesity and Sedentary Lifestyle
5.3. Lipodystrophic Disorders
5.3.1. Genetic Disorders
5.3.2. Acquired Disorders

6. Diabetes Mellitus
6.1. Type 1 Diabetes Mellitus
6.1.1. Chylomicron Metabolism
6.1.2. VLDL Metabolism
6.2. Type 2 Diabetes Mellitus
6.2.1. Chylomicron Metabolism
6.2.2. VLDL Metabolism
6.2.3. Small LDL Particles
6.2.4. Reduced HDL-C

7. Metabolic Syndrome
7.1. Prevalence of Elevated Triglyceride in MetS
7.2. Prognostic Significance of Triglyceride in MetS

8. Chronic Kidney Disease

These are all of the risk factors. Pretty much all of them, aside from genetic disorders are related to too much intake overall calories — obesity and sedentary lifestyle, diabetes, metabolic syndrome, and chronic kidney disease.

All of these are co-morbid with each other. For example, as obesity increases the risk of diabetes increases usually because of increased insulin resistance. The same is true of metabolic syndrome with accumulation of intra-visceral fat in the abdomen and effect it has on metabolism. When you have a lot more blood vessels needed to supply the fat cells, blood pressure is increased. Sustained increased blood pressure can kill kidney cells and lead to chronic kidney disease.

9. Interrelated Measurements and Factors That Affect Triglycerides

9.1. Non–HDL-C, Apo B, and Ratio of Triglycerides to HDL-C

As discussed previously in this statement, TRLs and RLPs in particular are atherogenic. Therefore, when a high-triglyceride profile is assessed, it is important to assess the overall atherogenicity of plasma. Both non–HDL-C (non–HDL-C=TC−HDL-C), which is a summary measure of all the cholesterol carried in apo B–containing particles, and directly measured apo B levels can be used for this purpose.

9.1.1. Non–HDL-C
9.1.2. Apo B
9.1.3. Ratio of Triglycerides to HDL-C

These are the factors that they recommend watching to look at atherogenic risk in patients.

Basically, looking at “other” types of HDL, Apo B, and triclyderide to HDL-C ratios. These are what you can look for on detailed blood panels.

However, I find it particularly interesting because of all of the research that was stated above about VLDL and they don’t mention it here. In particular, it’s been shown in at least observation studies that VLDL is an independent and strong risk factor in at least 2 studies that I am aware of. One, Two.

CONCLUSIONS: In a large Chinese cohort, elevated VLDL cholesterol was found to be significantly associated with elevated CHD risk, similar to that observed with LDL cholesterol. CHD risk was further amplified when elevated VLDL cholesterol was combined with elevated LDL cholesterol and/or the presence of major CVD risk factors.

CONCLUSION: These results suggest that an increased number of VLDL particles is strongly associated with CHD, independently of traditional risk factors or newly recognized atherogenic lipoproteins, such as IDL or small, dense LDL, in Japanese men.

If you are looking at a blood panel, VLDL levels especially with elevated LDL and triglycerides are something you want to look for too. This is along with Apo B, non-HDL C, and triglyceride to HDL-C ratios.

I’m skipping a few sections because the next few are about special populations. Going right to the food section and summarizing them for everyone:

13. Dietary Management of Hypertriglyceridemia
13.1. Dietary and Weight-Losing Strategies
13.1.1. Weight Status, Body Fat Distribution, and Weight Loss

13.2. Macronutrients
13.2.1. Total Fat, CHO, and Protein
13.2.2. Mediterranean-Style Dietary Pattern

13.3. Type of Dietary CHO
13.3.1. Dietary Fiber
13.3.2. Added Sugars
13.3.3. Glycemic Index/Load
13.3.4. Fructose

13.4. Weight Loss and Macronutrient Profile of the Diet
13.5. Alcohol
13.6. Marine-Derived Omega-3 PUFA
13.7. Nonmarine Omega-3 PUFA
13.8. Dietary Summary

  • Remove trans-fats —  One intervention is to eliminate dietary trans fatty acids, which increase triglycerides and atherogenic lipoproteins (ie, lipoprotein[a], LDL-C)382 and are linked to increased cardiovascular risk.383
  • Lose weight — A weight loss of 5% to 10% results in a 20% decrease in triglycerides, approximately a 15% reduction in LDL-C, and an 8% to 10% increase in HDL-C.386
  • Eat enough fat — In this analysis comparing low-fat, high-CHO diets versus higher-fat diets, for every 5% decrease in total fat, triglyceride level was predicted to increase by 6% and HDL-C to decrease by 2.2%. In a subsequent meta-analysis of 30 controlled feeding studies in patients with or without T2DM (n=1213), a moderate-fat diet (32.5% to 50% of calories from fat) versus a lower-fat diet (18% to 30% of calories from fat) resulted in a decrease in triglyceride level of 9.4 mg/dL (range from −6.1 to −12.2 mg/dL, P<0.00001) in those without T2DM391; however, in those with T2DM, the moderate-fat diet resulted in greater triglyceride reduction (−24.8 mg/dL, P<0.05) than seen with the low-fat diet.391 Lastly, in a large meta-analysis of 60 controlled feeding studies,392 replacement of any fatty acid class with a mixture of dietary CHOs increased fasting triglyceride levels. Specifically, for each 1% isoenergetic replacement of CHOs, decreases in triglyceride levels resulted with saturated fat (SFA; 1.9 mg/dL), MUFA (1.7 mg/dL), or PUFA (2.3 mg/dL) interchange (all P<0.001), which translated into an approximate 1% to 2% decrease in triglyceride levels.
  • Don’t eat a lot of carbohydrates — The evidence statement from ATP III relative to dietary CHOs conveyed the following message: “… [V]very high intakes of carbohydrate (>60 percent of total calories) are accompanied by a reduction in HDL cholesterol and a rise in triglyceride […] Accordingly, the recommendation by ATP III for dietary CHO was, “Carbohydrate intakes should be limited to 60 percent of total calories. Lower intakes (eg, 50 percent of calories) should be considered for persons with the metabolic syndrome who have elevated triglycerides or low HDL cholesterol.”221
  • Avoid high carbohydrates if you have elevated triglycerides — Berglund et al393 evaluated a high-CHO (54% of calories) and low-fat (8% SFA) diet versus a high-MUFA (37% of calories from fat; 22% MUFA, 8% SFA) and average American (37% of calories from fat; 16% SFA) diet in individuals with any combination of HDL-C ≤30th percentile, triglyceride levels ≥70th percentile, or insulin ≥70th percentile. Although triglyceride levels were not affected by the MUFA diet compared with the average American diet, they were higher on the CHO diet than with either the average American diet or the MUFA diet (7.4% and 12%, respectively; P<0.01 for both).
  • If you are eating high carbohydrates, the fiber from vegetables and fruits and/or unsaturated fatty acids may help — Thus, although many studies of high-CHO diets have shown increases in triglyceride levels, others (eg, DASH, OmniHeart, and WHI) have shown no effect. This discrepancy may reflect higher fiber intake (≈30 g/d; DASH, OmniHeart), higher protein intake (>15% of energy; DASH, OmniHeart, WHI), or a combined effect. Notably, the dietary patterns in DASH, OmniHeart, and WHI were high in fruits and vegetables, as well as grains (including whole grains). Results also suggest that moderate intake of predominately unsaturated fat (30% to 35% of energy or more) and plant-based proteins (17% to 25% of energy) may produce a triglyceride-lowering effect.
  • They still love the Mediterranean diet — [With a few exceptions], implementation of a Mediterranean-style diet versus a low-fat diet is more commonly associated with an approximately 10% to 15% lowering of triglycerides and a reduced prevalence of hypertriglyceridemia.
  • Get your fiber — In 7 studies (n=98) that compared moderate CHO and high fiber versus moderate CHO and low fiber, triglyceride levels decreased by 8% in the high-fiber groups. Similarly, in 9 studies (n=119) that compared high CHO and high fiber versus moderate CHO and low fiber, triglyceride levels decreased 13% in the high-fiber group. Therefore, these data support a triglyceride-lowering effect for dietary fiber in individuals with T2DM.
  • Remove as much sugar as possible from your diet — Consumption of added sugars has increased markedly in the United States from 1977–1978, when it was 10.6% of calories, to the current intake of 15.8% of calories.407,408 The American Heart Association recommends limiting added sugars to fewer than 100 calories daily (ie, 6 tsp) for women and 150 calories daily (9 tsp) for men (≈5% of total energy).9 The association of added sugars with increased obesity, T2DM, dental carries, and decreased diet quality is evident, which is part of the evidence base for recommendations made by other organizations to limit added sugars.409,410 […] The lowest triglyceride levels were observed when added sugar represented <10% of total energy. Conversely, higher triglyceride levels (5% to 10%) were observed when added sugar represented a greater proportion of energy intake.
  • Glycemic Index/Load is still controversial — For example, the Insulin Resistance Atherosclerosis Study419 found GL but not GI to be positively associated with triglycerides, whereas in the Whitehall II Study, GI but not GL correlated with triglyceride levels.420 A Cochrane review of 15 RCTs from 1982 to 2003 assessing the relationship between low-GI diets and lipids found no evidence that low-GI diets affected plasma triglycerides421; however, 2 subsequent studies reported lower triglyceride levels with low-GI diets.422,423 The relationship between GI/GL and triglycerides also remains unresolved in patients with T2DM, with 1 meta-analysis having identified a 6% reduction in triglyceride level in low- versus high-GI diets406 but another study finding no appreciable differences in triglyceride levels in 162 subjects with T2DM assigned to a low- or high-GI diet.424
  • Limit fructose in your diet  — In an extensive meta-analysis of 60 studies that evaluated the effects of fructose consumption on triglyceride levels, intakes ≤100 g/d had no significant effects on fasting plasma triglycerides. The lack of effect was demonstrated irrespective of whether fructose replaced starch, sucrose, or glucose. In contrast, intakes of fructose that exceeded 100 g/d revealed a dose-related increase in plasma triglycerides.428 Similarly, in the 12 studies that monitored ppTG, a dose-dependent increase was observed above the 50-g fructose dose.428 These data support limiting fructose in men and women with borderline or elevated triglyceride levels (Figure 5). A list of fructose-containing products is provided in Table 9.
  • Low carb diets have better triglyceride reducing effects short term, but long term they’re the same. Pick a diet that leads to significant and sustained weight loss —  A meta-analysis of RCTs that evaluated low-CHO versus low-fat (<30% of energy) diets found greater reductions in triglyceride levels on the low-CHO diet.435 Consistent with these findings, Bonow and Eckel434 concluded that low-CHO diets produced a more robust triglyceride-lowering effect than low-fat diets despite a similar magnitude of weight loss after 1 year. […] The effects of a Mediterranean-style weight loss diet were compared with low-CHO and low-fat energy-restricted diets.439 After 6 months, triglyceride levels were reduced the most in the low-CHO group (22%), but after 12 months, similar reductions were observed in both the low-CHO and Mediterranean-style groups, with minimal change in the low-fat group. Two additional studies evaluated 4 popular weight loss diets440,441 in free-living subjects for 1 year. Dansinger et al440 studied the effects of the Atkins diet, the Zone diet, the Weight Watchers diet, and the very low-fat Ornish diet on weight loss and CVD risk factors. Weight loss was similar after 12 months (4.8 to 7.3 kg) for all 4 diets. Although significant reductions in triglycerides occurred after 2 months on the Atkins and Zone diets, these effects were no longer significant after 12 months. In the study by Gardner et al,441 which compared the Atkins, Zone, LEARN (Lifestyle, Exercise, Attitudes, Relationships, and Nutrition) and Ornish diets, weight loss was greatest on the Atkins diet (4.7 kg) followed by LEARN (2.6 kg), Ornish (2.2 kg), and Zone (1.6 kg), with corresponding reductions in triglyceride levels (3% to 23%). Thus, diets that produce significant and sustained weight loss offer the most favorable reductions in triglyceride levels.
  • Moderate alcohol consumption (< 1oz/day) may lower risk, whereas high consumption (>1oz/day) increases risk. Alcohol abusers should abstain. — Prospective studies have demonstrated an inverse relationship between moderate alcohol consumption (ie, up to 1 oz daily) and CVD.442 In evaluating the relationship between alcohol consumption and triglycerides, some studies have shown no association,443,–,445 whereas others found modestly lower triglyceride levels in women who consumed up to 0.6 oz daily.446 At higher intakes, triglyceride levels increase,447,448 and Rimm et al449 estimated that ingestion of 1 oz/d would correspond to a 5% to 10% higher triglyceride concentration than found in nondrinkers. […] In contrast, alcohol abuse may be associated with hypertriglyceridemia; nearly 1 in 5 hospitalized alcoholics have triglyceride levels exceeding 250 mg/dL.450 An exaggerated rise in triglycerides occurs in the setting of excess alcohol intake combined with a meal high in saturated fat.
  • Fish oil helps, non-marine such as plant based (flax and other seeds do not) — In a comprehensive review of human studies, Harris454 reported that ≈4 g of marine-derived omega-3 PUFA per day decreased serum triglyceride concentrations by 25% to 30%, with accompanying increases of 5% to 10% in LDL-C and 1% to 3% in HDL-C. A dose-response relationship exists between marine-derived omega-3 PUFA and triglyceride lowering, with an approximate 5% to 10% reduction in triglycerides for every 1 g of EPA/DHA consumed455; efficacy is greater in individuals with higher triglyceride levels before treatment.455,–,457 Note: Supplementation via O-3s hasn’t been evaluated by RCTs yet though. […] Non–marine-based omega-3 PUFA is derived from α-linolenic acid, a plant-based PUFA found in canola, chia, flaxseed, perilla, rapeseed, soybeans, walnuts, and purslane.465,466 Yet non–marine-based PUFAs have not demonstrated consistent reductions in triglycerides467; this may reflect very low conversion rates of α-linolenic acid and its intermediary, stearidonic acid,468 to the active triglyceride-lowering omega-3 compounds EPA and DHA.469 Therefore, if omega 3 PUFAs are used for triglyceride lowering, they should be exclusively marine-derived EPA and/or DHA.

13.8. Dietary Summary

Overall, optimization of nutrition-related practices can result in a marked triglyceride-lowering effect that ranges between 20% and 50%. These practices include weight loss, reducing simple CHO at the expense of increasing dietary fiber, eliminating industrial-produced trans fatty acids, restricting fructose and SFA, implementing a Mediterranean-style diet, and consuming marine-derived omega-3 PUFA (Table 11). Dietary practices or factors that are associated with elevated triglyceride levels include excess body weight, especially visceral adiposity; simple CHOs, including added sugars and fructose; a high glycemic load; and alcohol.

  • Exercise is most effective in lowering triglycerides (eg, 20% to 30%) when baseline levels are elevated (ie, >150 mg/dL), activity is moderate to intensive, and total caloric intake is reduced — For example, an optimal fasting triglyceride level (eg, <100 mg/dL) was associated with minimal (ie, <5%) reductions in postexercise triglyceride levels compared with greater (ie, 15% to 20%) reductions if baseline triglyceride levels exceeded 150 mg/dL.474 Moreover, in a study of 2906 middle-aged men, moderately intensive activity (ie, jogging 10 miles weekly) versus no activity was associated with a 20% lower fasting triglyceride level; the highest activity level (>20 miles weekly) was also accompanied by the lowest mean fasting triglyceride level (86 mg/dL).475 Higher baseline triglyceride levels (mean 197 mg/dL) also translated into significant triglyceride reductions (26%) in a 6-month trial of overweight subjects who walked 12 miles weekly at 40% to 55% of peak oxygen consumption.476 However, other studies evaluating walking duration, frequency, and intensity (30 minutes daily at a maximum 65% to 75% of age-predicted heart rate) in the absence of weight loss did not demonstrate differences in postexercise triglyceride levels.477 Similarly, increasing energy expenditure through physical activity without changing energy intake did not result in lower triglyceride levels if baseline levels were relatively normal (ie, mean 110 mg/dL). However, a reduction in energy intake (300 kcal/d) resulted in a 23% reduction in fasting triglyceride levels during the 1-year trial.478 Additional benefits of exercise include reduction in the ppTG response and attenuation of the triglyceride elevations observed after consumption of a low-fat, high-CHO diet.479 In fact, 60 minutes of aerobic exercise daily abolishes the CHO-induced increases in TRL.480 Overall, exercise is most effective in lowering triglycerides (eg, 20% to 30%) when baseline levels are elevated (ie, >150 mg/dL), activity is moderate to intensive, and total caloric intake is reduced.481

Note: I skipped the section on statins and fibrates. I also skipped prevention strategies which basically describes eliminating excess sugar and trans-fats from schools.

Conclusions

Cardiovascular disease and atherosclerosis arises from a dysfunctional overload of the body’s dietary lipid transport systems.

When too many calories are ingested over long periods of time, this raises production of VLDL within the liver. VLDL is converted into different various different triglyceride rich lipids within the blood stream which are atherogenic. Overall, it is the triglyceride rich lipids (TRLs) with certain receptors like apo B, CE, Apo CIII and such that are pro-inflammatory and therefore most likely the cause of said atherosclerosis. In particular these are summarized by:

  • 4.5.1. Remnant Lipoprotein Particles — after VLDL is made and split up in the blood stream
  • 4.5.2. Apo CIII — major component of circulating TRLs and correlated with increased blood triglyceride levels
  • 4.5.3. Macrophage LPL — increase the expression of inflammatory proteins, adhesion molecules, and coagulation factors in endothelial cells or monocytes and macrophages

What to look for in assessing risk, especially on blood panels:

  • 9.1.1. Non–HDL-C
  • 9.1.2. Apo B
  • 9.1.3. Ratio of Triglycerides to HDL-C
  • VLDL as a strong independent risk factor, especially in combination with high LDL and triglyceride levels

Regarding dietary modification and exercise:

  • Remove trans-fats
  • Lose weight
  • Eat enough fat
  • Don’t eat a lot of carbohydrates (>50-60% CHO)
  • Avoid high carbohydrates if you have elevated triglycerides (>50% CHO)
  • If you are eating high carbohydrates, the fiber from vegetables and fruits and/or unsaturated fatty acids may help
  • They still love the Mediterranean diet
  • Get your fiber
  • Remove as much sugar as possible from your diet
  • Glycemic Index/Load is still controversial
  • Limit fructose in your diet
  • Low carb diets have better triglyceride reducing effects short term, but long term they’re the same. Pick a diet that leads to significant and sustained weight loss
  • Moderate alcohol consumption (< 1oz/day) may lower risk, whereas high consumption (>1oz/day) increases risk. Alcohol abusers should abstain.
  • Fish oil helps, non-marine such as plant based (flax and other seeds do not). Carlson’s fish oil is one I have used before. High DHA/EPA content. Doesn’t taste nasty.
  • Exercise is most effective in lowering triglycerides (eg, 20% to 30%) when baseline levels are elevated (ie, >150 mg/dL), activity is moderate to intensive, and total caloric intake is reduced

Overall, optimization of nutrition-related practices can result in a marked triglyceride-lowering effect that ranges between 20% and 50%. These practices include weight loss, reducing simple CHO at the expense of increasing dietary fiber, eliminating industrial-produced trans fatty acids, restricting fructose and SFA, implementing a Mediterranean-style diet, and consuming marine-derived omega-3 PUFA (Table 11). Dietary practices or factors that are associated with elevated triglyceride levels include excess body weight, especially visceral adiposity; simple CHOs, including added sugars and fructose; a high glycemic load; and alcohol.

Thoughts on this scientific statement & the conclusion

  • VLDL wasn’t a huge risk factor for heart disease on blood panels. This is a glaring oversight that I had to add into the conclusion. I already covered the reason why above.
  • They still say to restrict saturated fatty acids, when there is no evidence in their above study that says to restrict fatty acids. The only evidence they’re going on is maybe a slightly reduction of elevated triglycerides compared to replacement of saturated fatty acids with mono and polyunsaturated fatty acids. This is not something I would worry about. SFA > excess carbohydrates.
  • Glycemic Index/Load is controversial, but they still say to avoid high GL/GI. Alright, fine.
  • They discussed “some” alternative diets like Atkins, Zone, and so on, but they did not touch any of the Paleo studies that show better results than other counterparts, even in diabetes. This is very questionable. However, given the data, I do not think that the overall benefits are necessarily because of Paleo in particular but overall sustained weight loss and exercise.
  • They only looked at aerobic exercise and didn’t take a look at strength training or analyze anything in terms of increased muscle mass. Probably beyond the scope of this statement, but it is something to look for.

TL;DR:. Do NOT be obese. Pretty much everything stems from being obese. Find a way to lose weight that is sustainable and permanent, exercise (aerobic or otherwise), and aim for lots of vegetables, fruits, remove refined sugars, and get enough fats and protein in your diet. Watch for various factors on your blood panels that can indicate potential risk, especially VLDL.


This article was originally published May 24th, 2010 on Eat Move Improve. Updated Jan 2017. 

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Author: Steven Low

Steven Low, author of Overcoming Gravity: A Systematic Approach to Gymnastics and Bodyweight Strength (Second Edition), is a former gymnast who has performed with and coached the exhibitional gymnastics troupe, Gymkana. Steven has a Bachelor of Science in Biochemistry from the University of Maryland College Park, and his Doctorate of Physical Therapy from the University of Maryland Baltimore. Steven is a Senior trainer for Dragon Door’s Progressive Calisthenics Certification (PCC). He has also spent thousands of hours independently researching the scientific foundations of health, fitness and nutrition and is able to provide many insights into practical care for injuries. His training is varied and intense with a focus on gymnastics, parkour, rock climbing, and sprinting.