Postprandial Lipoproteins: The storm after the quiet!
Part 1 - Fats

Postprandial, or after-eating, responses represent an exciting new territory for heart disease
prevention. It is also largely unexplored territory for the Track Your Plaque program.
Management of diet would be woefully incomplete without having some
understanding of postprandial phenomena.

Clinical studies suggest that postprandial responses play a major role in causing
coronary plaque. We begin our exploration of this somewhat complex world with
postprandial lipoproteins, the metabolic handling of fats after eating.
In a future Special Report, we will explore postprandial handling of carbohydrates.
 

Important points

• The postprandial, or after-eating, period is characterized by distinct changes in lipoproteins, triglycerides, blood coagulation, inflammatory responses, and arterial responses, all of which have been implicated as contributors to plaque and heart disease.
• Increased fasting triglycerides, LDL, small LDL, and low HDL can be markers for potential postprandial lipoprotein abnormalities.
• While excessive carbohydrate consumption leads to postprandial abnormalities in the long-term, fats are the immediate determinant of postprandial responses. The threshold for excessive fat intake in a single meal is likely in the range of 25-50 grams; more than this amount of fat in a meal and excessive postprandial phenomena develop. Non-fasting triglycerides of 85 mg/dl or less are desired.
• Monounsaturated fats, such as oleic acid from olive oil, provoke the least postprandial surges, while saturated fats provoke the greatest. Cholesterol intake delays clearance of postprandial particles. Oxidized fats, principally the polyunsaturates, generate more oxidized postprandial particles that can be incorporated into atherosclerotic plaque.
• Omega-3 fatty acids, EPA and DHA, but not linolenic acid (flaxseed), reduce the magnitude of postprandial lipoproteins.
• Weight loss and exercise also reduce postprandial responses, as do green tea and diacylglycerols.

You’ve just had dinner, now full and satisfied. You sit down to relax, perhaps have a glass of wine.

What becomes of the foods you’ve just ingested? How are the chewed chicken, beef, broccoli, cheese, olive oil, etc., processed and converted into the various components of your body? Do different foods or different habits, such as exercise, influence how foods are processed and whether they contribute to coronary plaque?

The time period of incorporation of food materials into our body, starting with the action of hydrochloric acid and digestive enzymes, is the postprandial period, the several hours after a meal in which foods make their way to the lymph system, the blood, then to the liver, muscle, and other organs. Much of the day, 12-18 hours, is spent in the postprandial state if there are three meals per day.

Blood is usually examined after a period of fasting, 8 to 12 hours of not eating with blood samples obtained the following morning, even though no data ever demonstrated the superiority of fasting levels. The Friedewald calculation for LDL cholesterol is also based on having a fasting triglyceride value; postprandial values essentially negate the value of the Friedewald calculation.

Up until now, we’ve relied on levels of intermediate-density lipoproteins (IDL) or remnant lipoproteins (RLP) on fasting lipoprotein panels, surrogates for postprandial particles that provide some insight into postprandial metabolism. But this fails to directly examine the phenomena of the crucial postprandial period, a period that displays dramatic variation in lipoprotein composition, even among people with similar fasting values.

Dietary fats are composed primarily of triglycerides. Triglycerides are therefore released into the bloodstream during the postprandial period, not during periods of fasting. Because postprandial particles (chylomicrons, chylomicron remnants, and VLDL) are all triglyceride-rich, measurement of triglycerides can serve as the most ready means to assess postprandial responses. Triglycerides will therefore be the most available index for us to assess postprandial patterns in the Track Your Plaque program.

Glucose (blood sugar) provides yet another aspect of postprandial responses that can influence cardiovascular risk and plaque growth or regression. Glucose responses are determined largely by carbohydrate intake and to a lesser degree by fat and protein intake and are associated with oxidative stress, inflammatory responses, and endothelial dysfunction. The important issue of carbohydrates and glucose responses will be considered in another Track Your Plaque Special Report.
 

What happens after you eat?

First, chewed, swallowed food is subject to stomach acid and enzymes like pepsin and amylase. Passing into the small intestine, bile acids (produced by the liver and stored in the gallbladder) are secreted and further break food down. Fats are dispersed into very small droplets by the action of bile acids.

Triglycerides from dietary fat are absorbed across the small intestinal lining where chylomicrons are formed, large particles consisting principally of triglycerides and the unique intestinal protein, apoprotein B48 (apoB48). Chylomicrons are released by the intestinal cells and enter the lymph system. Chylomicrons then travel for a short distance and enter the blood stream.

The large chylomicron particles themselves likely have no potential for causing plaque. Once in the bloodstream, chylomicrons are subject to the action of the enzyme, lipoprotein lipase, residing along the artery wall, that removes triglycerides and yields chylomicron remnants.

In particular, chylomicron remnants that remain after the action of lipoprotein lipase have been found to be associated with endothelial dysfunction, progression of coronary atherosclerotic plaque, and have been recovered from within plaque itself, suggesting a causal or contributing role (Batt 2004). Chylomicron remnants appear to enter the artery wall with the same rapidity as LDL particles (Mamo 1994) but can deliver 5-20 greater cholesterol than an LDL particle (Wilhelm 2003). Chylomicron remnants in the blood stream are normally cleared by the liver, followed by removal of triglycerides to form VLDL particles.

While chylomicrons are the particles that initially form after a meal, by two hours after a meal, VLDL particles outnumber chylomicrons substantially. (Most triglycerides measured in the blood stream are therefore provided by VLDL, not chylomicrons nor their remnants.) VLDL are, like chylomicrons, subject to the triglyceride removing effects of lipoprotein lipase, progressing from large VLDL particles to smaller, followed by “conversion” to IDL and LDL particles.

If substantial carbohydrates are included in a meal, then the process of de novo lipogenesis develops as an adaptive response to the high carbohydrate intake, since the body has little capacity for carbohydrate storage. In de novo lipogenesis, sugars are converted to fatty acids, which are in turn used by the liver to produce triglycerides and VLDL (Timlin 2005). This can yield greater triglyceride and VLDL levels at 4 hours postprandial and beyond, especially with carbohydrate intakes of 50% of calories or greater, or if overweight and/or insulin resistance are present (Perez-Martinez 2009;Volek 2004).

Because postprandial particles are triglyceride-rich, the more marked the postprandial response of chylomicrons, VLDL, and triglycerides, the more likely triglyceride-enriched small LDL particles will form, even within hours of the postprandial response (Blackburn 2003). Up to 50% of the size variation of LDL particles may be influenced by postprandial triglyceride-rich lipoproteins (Karpe 1993). Postprandial responses also influences HDL: the greater the triglyceride response, the lower the HDL and more triglyceride-rich, leading to smaller HDL particles (Patsch 1984). Thus, improved postprandial metabolism might lead to benefits for improving LDL and HDL levels and size.

Liver clearance of chylomicron remnants are dependent on the LDL receptor; greater numbers of LDL particles may therefore compete with chylomicron remnants for the liver LDL receptor and delay chylomicron clearance (César 2006). Increased dietary cholesterol, e.g., 3 egg yolks, can also impair clearance of chylomicron remnants, increased blood “residence time” by 52% (César 2006).

Along with chylomicrons, chylomicron remnants, and VLDL, changes in blood coagulation (clotting) occur in the postprandial period. Clotting factor VII is activated, as well as plasminogen activator inhibitor-I, both of which encourage blood clot formation (Silveira 2001).

Other phenomena that develop during the hours of the postprandial period include:

• Increased release of soluble adhesion molecules (SAM): Soluble adhesion molecules “invite” inflammatory white blood cells to enter plaque. One study compared SAM release after safflower (rich in polyunsaturated omega-6 fatty acids and linoleic acid) to olive oil (rich in monounsaturates and oleic acid); the safflower provoked a more vigorous SAM response (Jagla 2001).
  
  
• Endothelial dysfunction: Greater magnitude of postprandial chylomicron, chylomicron remnant, and VLDL responses, the greater the endothelial-impairing effect (i.e., reduced arterial enlargement in response to a challenge). This is believed to be due to the greater oxidative stress induced in the postprandial period, with greater blood glucose and triglyceride-containing lipoproteins that trigger superoxide anion (O2-) that inactivates endothelial relaxing factor, nitric oxide (NO) (Ceriello 2002).

Chylomicrons, chylomicron remnants, and VLDL are all composed mostly of triglycerides. Measuring triglycerides thereby provides an indirect method of assessing all the triglyceride-containing particles that develop. Following a meal, the peak triglyceride level is reached after 3-4 hours; this is the time point at which triglycerides are usually assessed. (Assessing “area under the curve,” while more accurate, requires multiple values, an impracticality for most people.) Triglycerides can require up to 12 hours to return to pre-meal levels, especially if obesity, insulin resistance, and diabetes are present (Campos 2005).

Several studies have demonstrated that both fasting triglycerides and postprandial triglycerides are associated with greater likelihood of increased carotid intimal-medial thickness and carotid plaque (Mori 2005; Sharrett 1995). Compared to control subjects, men with coronary artery disease have been shown to have greater postprandial triglyceride responses (Groot 1991) Four-hour and 6-hour triglyceride responses were 20% and 52% greater after a fat challenge in subjects with coronary disease (Patsch 1992). Postprandial responses also correlate with progression of coronary disease by angiography (Karpe 1994).

Two large studies have demonstrated the graded increased cardiovascular risk revealed by non-fasting postprandial triglyceride levels. The Women’s Health Study of over 26,000 females showed that triglycerides measured at 2-4 hours after a (non-standardized) meal had the greatest predictive value for future cardiovascular events, with the highest values predicting 6.27-fold greater risk (Bansal 2007). Fasting triglycerides were also predictive for events, but after other risk factors were factored out, such as BMI, HDL, CRP and presence of diabetes, fasting triglycerides lost their independent predictive value. Non-fasting triglycerides, however, maintained substantial predictive value. Interestingly, cardiovascular risk began to increase with fasting triglycerides ≥74 mg/dl, non-fasting (postprandial) triglycerides of ≥86 mg/dl. Highest risk developed with fasting triglycerides ≥185 mg/dl, non-fasting of ≥215 mg/dl.

In the Copenhagen City Heart Study, 7587 women and 6394 men were followed for 26 years (Nordestgaard 2007). For both men and women, cardiovascular risk increased with non-fasting triglycerides of 88 mg/dl or greater, with 2.2-fold increased risk for heart attack in the range of 88-176 mg/dl for females, 1.6-fold increased risk for heart attack for males. Graded risk developed with increasing non-fasting triglyceride levels. At all levels of non-fasting triglycerides, the risk for females was greater than that for males.

Note that, in the two above studies, there is remarkable agreement that increased cardiovascular risk begins to develop at the 86-88 mg/dl non-fasting triglyceride range. Also, in both the Women’s Health Study and the Copenhagen City Heart Study, participants ate their usual diets, in which fat intake tends to be less than that contained in high-fat standardized test meals, which usually contain 1 gram fat per kilogram body weight (0.45 grams fat per pound body weight). Non-fasting or postprandial triglycerides in these studies are therefore lower compared to controlled meal studies.

Studies that use a fat challenge demonstrate higher postprandial triglycerides in normal (i.e., non-diabetic, non-alcoholic, non-obese, no lipid disorders) control subjects than observed in people eating their usual diet. The following peak postprandial triglyceride values have been observed after high-fat test meals (usually at 3-4 hours postprandial):

• 162.8 mg/dl—After 8 weeks of high-monounsaturated fat adaptation + 2500 mg/day EPA + DHA); fat challenge total 123 grams fat (52 g saturated, 59 g monounsaturated, 12 g polyunsaturated) (Volek 2000). Note the high quantity of total fat in the fat challenge.
• 150-240 mg/dl after fat test meal (1 g/kg bodyweight) in slightly overweight subjects (Park 2003).
• 119 mg/dl after 62 g fat test meal (Brown 1991).
• 74 mg/dl after 15 g fat test meal (no different than after non-fat test meal); 123 mg/dl after 30 g test meal; 133 mg/dl after 40 gram test meal; 155 mg/dl after 50 gram test meal (Dubois 1998).
• 150 mg/dl after 83.5% fat test meal (62.5 g fat per m2 body surface area) (Kolovou 2005). 263.3 mg/dl after same fat test meal (Patsch 1992).
• 142 mg/dl following test meal including 50 g fat (20 g olive oil, 30 g fish oil) (Heath 2007). Note that acute fish oil administration did not substantially modify the response, distinct from the chronic response.
• 89 mg/dl after 25 g fat, 75 g carbohydrate meal in normal controls with very low BMI (21.4) (Harano 2006).
• 169 mg/dl after 1 g fat/kg meal, mostly olive oil; BMI 24.5 (Perez-Martinez 2009).
• 212 mg/dl in younger (mean age 29 years), 314 mg/dl in older (mean age 66 years) subjects given 1 g/kg fat challenge (Cohn 1988).
• 178 mg/dl in overweight subjects (BMI 28.4) after 75 g fat meal
• 98 mg/dl after 50 g fat, 50 g carbohydrate challenge in mildly overweight, non-diabetic (BMI 27.9) subjects (Mohanlal 2004)

The wide variation in peak postprandial triglycerides among studies is due to differing populations with different age profiles, ApoE types, different weights, varying proportion of men vs. women, etc. Nonetheless, it appears that a per-meal fat intake “threshold” of approximately 25-50 grams fat per meal exists, below which postprandial triglycerides stay at low levels <100 mg/dl, while above 25 grams per meal postprandial triglycerides, and thereby triglyceride-rich lipoproteins, are triggered excessively, as judged by triglycerides.

The postprandial response differs between acute changes in diet composition vs. chronic. In other words, an abrupt change in meal composition will yield different postprandial responses than the same meal consumed habitually. Varying the fat composition of a meal acutely will substantially affect postprandial responses, with greater triglycerides and triglyceride-containing lipoproteins with increasing fat intake (Van Amelsvoort 1989). Following a high-fat diet, for example, will yield lower postprandial triglyceride levels after 8 weeks compared to the start, suggesting an accommodation process via activation of lipoprotein lipase (Volek 2000). However, once accommodation develops, it is not clear what level of fat intake can be accommodated without excessive provocation of postprandial lipoproteins to an undesirable degree. That question has not yet been answered.

Factors that affect postprandial lipoproteins

Want to read the rest of this Track Your Plaque Special Report? Already a member? CLICK HERE to log-in. Want to become a member? CLICK HERE Want to learn more about the benefits of membership? CLICK HERE

Copyright 2010, Track Your Plaque.