Non-fasting triglycerides have been proposed as a predictor of cardiovascular risk. In low-carb athletes and sedentary low-carbers, postprandial triglycerides rise to the same levels as those associated with higher cardiovascular risk in the general populattion. It is, however, not clear if higher postprandial triglycerides increase cardiovascular risk in people on low-carb diets.

Some claim that high amounts of fat consumed on low-carb high fat diets are safe and are really the best and the safest fuel. A larger question is whether this claim is true, or whether it is always true.

Trying to identify a particular type of lipoprotein, lipid or other marker as the ultimate causal factor in atherosclerosis has limited interest. The entire blood lipid picture changes in the states that are associated with metabolic disease. Multiple markers change. It is more productive to understand how we can improve the entire “metabolic picture”.

The postprandial triglyceride rise after a normal food intake and after “fat intake”.

Here is how the authors of a 2007 study describe the postprandial triglyceride rise after a normal food intake and after “fat intake”. Nordestgaard et al., 2007 (3):

During a fat tolerance test, plasma triglyceride levels reached a mean peak level of 2.3 mmol/L (203.5 mg/dL) 4 hours after fat intake, whereas in individuals from the general population the mean peak level was 1.6 mmol/L (61.8 mg/dL) 4 hours after normal food intake.

Triglycerides are expected to return to baseline 10 hours after a fat meal.

Triglycerides are expected to return to baseline 10 hours after a fat meal. But this does not always happens in people on low-carb, high-fat diets. Shaikh et al., 1001 (4):

Triglyceride levels normally return to baseline fasting levels at 10 hours after the fat meal.

The figure from Cohn et al., 1988 (6), seems to confirm that, at least for some people, total triglycerides return to baseline after 10 to 12 hours after a fat-rich meal.

Fig. 3. Separation of TRL apolipoproteins by gradient (4-22.5%) polyacrylamide gel electrophoresis. The gels for three subjects, with increasing magnitude of postprandial triglyceridemia, are shown in the three panels. Postprandial changes in TRL triglyceride concentration are shown in the graphs at the bottom of each panel. The five lanes on each gel correspond (from left to right) to TRL fractions isolated at 0, 3, 6, 9, and 12 hr after the ingestion of the fat-rich meal. Panel A: Fractions from 25-year-old female; total postprandial plasma triglyceridemia - 894 mg - hr/dl. Panel B: Fractions from 65-year-old female; total postprandial plasma triglyceridemia - 1578 mg - hr/dl. Panel C: Fractions from 25-year-old male; total postprandial plasma triglyceridemia - 3224 mg * hr/dl. The apolipoprotein bands are identified at the left of each gel. Alb., albumin. Source: Cohn, 1988. — Fig. 3. Separation of TRL apolipoproteins by gradient (4-22.5%) polyacrylamide gel electrophoresis. The gels for three subjects, with increasing magnitude of postprandial triglyceridemia, are shown in the three panels. Postprandial changes in TRL triglyceride concentration are shown in the graphs at the bottom of each panel. The five lanes on each gel correspond (from left to right) to TRL fractions isolated at 0, 3, 6, 9, and 12 hr after the ingestion of the fat-rich meal. Panel A: Fractions from 25-year-old female; total postprandial plasma triglyceridemia – 894 mg – hr/dl. Panel B: Fractions from 65-year-old female; total postprandial plasma triglyceridemia – 1578 mg – hr/dl. Panel C: Fractions from 25-year-old male; total postprandial plasma triglyceridemia – 3224 mg * hr/dl. The apolipoprotein bands are identified at the left of each gel. Alb., albumin. Source: Cohn, 1988.

“A major source of circulating triglycerides is dietary fat.”

Ridker, 2008 (1):

A major source of circulating triglycerides is dietary fat, which, after hydrolysis into free fatty acids and glycerides, is transported through the intestinal villi and absorbed by enterocytes, where these particles are synthesized into chylomicron-associated triglycerides for entry into the blood compartment and ultimately storage in adipose tissue.

A rise in chylomicron triglycerides that are derived from dietary fat in the experiments of Nowotny et al., 2013 (2).

The statement above by Ridker, 2008 (1), is correct and can be illustrated by a figure from Nowotny et al., 2013 (2) (below). We can, indeed, see a rise in chylomicron triglycerides that are derived from dietary fat (“per oral” or “po fat” in the experiments of Nowotny et al., 2013 (2)).

FIG. 1. Study protocol in experiments comparing high-fat oral loading with fat and LPS infusion. Source: Nowotny, 2013.

It is interesting to note that after “per oral fat” (“po fat: 100 mL of soy bean oil consumed within 10 min”) in the experiment by Nowotny et al., 2013, (the two figures above), total triglycerides did NOT change, while chilomycron triglycerides almost doubled by 180 minutes. Why?

There is also a contradiction with the citation above from Nordestgaard et al., 2007 (3), who wrote that after a fat tolerance tests, triglycerides rise to a peak of 2.3 mmol/L. Nordestgaard et al., 2007 (3), provide a reference for their statement. It is the study by Cohn et al., 1988 (6). What was the fat meal composition and who were the subjects in that study?

Well, it turns out that the “fat meal” contained 33.3% fat, 33.3% protein, and 33.3% carbohydrate (by weight). Cohn et al., 1988 (6):

After a 14-hr overnight fast, subjects were given a fat meal, containing 1.0 g of fat/kg body weight and 7.0 mg of cholesterol/kg (given as egg yolk powder). The fat was given as soybean oil to 12 sub- jects and as soybean oil plus cream (l:l, w/w) to the remaining 10 subjects. Since no differences were observed between subjects fed the two fat mixtures, data were ana- lyzed together for all 22 subjects. The amount of fat given was designed to be %-% of that which an average Ameri- can ingests per day. The meal was prepared as a formula milkshake with added flavoring. Polycose and egg white protein were added to the formula so that the meal contained 33.3% fat, 33.3% protein, and 33.3% carbohydrate (by weight) or 53% fat, 23.5% protein, 23.5% carbohy- drate (by energy).

Postprandial triglycerides, cholesterol and lipoproteins after a “fat-rich meal” in the study by Cohn, 1988 (6).

We have learned that Cohn et al., 1988 (6), used a “fat-rich” meal and not a fat-only meal. Therefore, we can not really compare the experiments of Nowotny et al., 2013 (2), and Cohn et al., 1988 (6). However, Cohn et al., 1988 (6), made a series of very informative measurements of postprandial blood triglycerides and lipoproteines. Below, we share several informative graphs and tables from their study (=Physiological Literacy).

Fig. 1. Chromogenicity of the TRL aptipopmteins. Increasing amounts of TRL protein were loaded onto gradient gels. Gels were electrophoresed, stained. and then scanned with a two-dimensional laser densitometer. In- tensity of staining for each protein band was measured in arbitrary units (am.), as the average of three measure- ments made on the same sample. Eaeh sample was run in duplicate. Data for the remaining TRL apolipoproteins (apoH, a@-IV, and apoA-I) are not shown. Linearity of staining was observed for all TRL apoIipopruteins when less than 45 fig of total TRL protein was loaded. Cohn, 1988.

TABLE 2. Ptasma mgtyceride, chdestd, apohpopmtein A-I and apolipopmtein B concentrations fdiowing the ingestion of thc fat-rich meal. Values am -s * SEM bor 22 subjects. Rcsults are signidy differrnt fmm zero-time by paired t-test: "Zero-hr concentrations were measured after a 14-br overnight fast, before the ingestion of the fat-rich meal. Source: Cohn, 1988. — TABLE 2. Ptasma mgtyceride, chdestd, apohpopmtein A-I and apolipopmtein B concentrations fdiowing the ingestion of thc fat-rich meal. Values am -s * SEM bor 22 subjects. Rcsults are signidy differrnt fmm zero-time by paired t-test: “Zero-hr concentrations were measured after a 14-br overnight fast, before the ingestion of the fat-rich meal. Source: Cohn, 1988.

TABLE 3. Postprandial changes in the triglyceride-rich lipoprotein (TRL) fraction after the fat-rich meal. Values are means f SEM for 22 subjects. Significantly different from zero time by paired t-test: , P < 0.05; ', P < 0.01; **', P < 0.001. "Zero-hr concentrations were measured after a 14-hr overnight fast, before the ingestion of the fat-rich meal. 'TRL apoB was measured by ELISA assay using a polyclonal antibody that recognized both apoB-100 and apoB-48. Source: Cohn, 1988. — TABLE 3. Postprandial changes in the triglyceride-rich lipoprotein (TRL) fraction after the fat-rich meal. Values are means f SEM for 22 subjects. Significantly different from zero time by paired t-test: , P

Fig. 2. Relationship between A) fasting plasma triglyceride concentra- tions and postprandial increases in plasma triglyceride concentration; B) fasting TRL triglyceride concentrations and postprandial increases in TRL triglyceride concentration; and C) fasting TRL apoB concentra- tions and postprandial increases in TRL apoB concentrations. A coefficient of correlation (r) is shown for each relationship, together with its level of statistical significance. Postprandial rise for each parameter was measured as the difference between zero-hour concentration and the maximum concentration observed postprandially. Source: Cohn, 1988.

Fig. 4. Change in triglyceride-rich lipoprotein (TRL), apoB-100, and apoB-48 concentrations in subjects fed a fat-rich meal. Relative TRL apoB-100 and apoB-48 concentrations were calculated as a percentage of their zero- hour (fasting) concentrations. Quantitation of TRL apoB-100 and apoB-48 was achieved by densitometric scanning of the apoB-100 and apoB-48 bands of polyacrylamide gradient gels after electrophoretic separation of the TRL apolipoproteins (see Methods). Each point represents the mean f SEM for 22 subjects. Significantly different from zero time by paired t-test: **P < 0.01, ***P < 0.001. — Fig. 4. Change in triglyceride-rich lipoprotein (TRL), apoB-100, and apoB-48 concentrations in subjects fed a fat-rich meal. Relative TRL apoB-100 and apoB-48 concentrations were calculated as a percentage of their zero- hour (fasting) concentrations. Quantitation of TRL apoB-100 and apoB-48 was achieved by densitometric scanning of the apoB-100 and apoB-48 bands of polyacrylamide gradient gels after electrophoretic separation of the TRL apolipoproteins (see Methods). Each point represents the mean f SEM for 22 subjects. Significantly different from zero time by paired t-test: **P

TABLE 4. Postprandial changes in TRL triglyceride, TRL apolipoprotein B, and TRL apoB-100/apoB-48 ratio in subjects grouped according to their magnitude of postprandial triglyceridemia". Values are means f SEM for seven subjects in group A, seven subjects in group B, and eight subjects in group C. Results are significantly different "Magnitude of postprandial triglyceridemia was measured by calculating the area between curve and baseline, from the graph of plasma triglyceride *Zero-hr measurements were made on plasma obtained after a 14-hr overnight fast, before ingestion of the fat-rich meal. 'TRL apoB was measured by ELISA assay using a polyclonal antibody that recognized both B-100 and B-48. dCalculated from the two-dimensional densitometric scans of polyacrylamide gradient gels. Source: Cohn, 1988. — TABLE 4. Postprandial changes in TRL triglyceride, TRL apolipoprotein B, and TRL apoB-100/apoB-48 ratio in subjects grouped according to their magnitude of postprandial triglyceridemia”. Values are means f SEM for seven subjects in group A, seven subjects in group B, and eight subjects in group C. Results are significantly different “Magnitude of postprandial triglyceridemia was measured by calculating the area between curve and baseline, from the graph of plasma triglyceride *Zero-hr measurements were made on plasma obtained after a 14-hr overnight fast, before ingestion of the fat-rich meal. ‘TRL apoB was measured by ELISA assay using a polyclonal antibody that recognized both B-100 and B-48. dCalculated from the two-dimensional densitometric scans of polyacrylamide gradient gels. Source: Cohn, 1988.

Fig. 5. Change in triglyceride-rich lipoprotein (TRL) apolipoprotein concentrations in subjects fed a fat-rich meal. Relative TRL apolipo- protein concentrations were calculated as a percentage of their zero-hour (fasting) concentrations. Each point represents the mean f SEM for 22 subjects. Significantly different from zero time by paired t-test: 'P < 0.05, "*P < 0.001. Source: Cohn, 1988. — Fig. 5. Change in triglyceride-rich lipoprotein (TRL) apolipoprotein concentrations in subjects fed a fat-rich meal. Relative TRL apolipo- protein concentrations were calculated as a percentage of their zero-hour (fasting) concentrations. Each point represents the mean f SEM for 22 subjects. Significantly different from zero time by paired t-test: ‘P

The rise in postprandial triglycerides and atherogenesis.

Already cited above Ridker, 2008 (1), goes on with his description of the possible role of triglycerides in cardiovascular risk, but some of his statements are questionable. For example:

“Postprandial lipids and their associated partially hydrolyzed chylomicron remnants appear to promote early atherogenesis, adversely affect endothelial function, associate with atherogenic small LDL particles, and correlate with both prothrombotic and proinflammatory biomarkers, including factor VII, plasminogen activator inhibitor-1, and C-reactive protein.”

Indeed, on low-carb diets, postprandial lipids, including triglycerides, do rise considerably after meals. But it is not clear if this rise is associated with atherogenesis.

For example, in the FASTER study by Volek et al., 2015 (5), two groups, a group of low-carb athletes and a group of high-carb athletes, were given a meal 90 minutes before the two groups started a long run on a treadmill. By the time point “90 minutes”, triglycerides rose a lot more in the low-carb group.

Circulating concentrations of plasma triglycerides (mmol/L) in a group of low-carb (LC) athletes and in a group of high-carb (HC) athletes. *Indicates significant (P = 0.000) difference between HC and LC values at that time point. Source: Volek et al., 2015.

Note, however, that the differences in triglycerides did not reach statistical significance. The size of the groups may not have been big enough and, as we learned from the study, some of the athletes may have been insulin-resistant.

Some of the athletes in the FASTER study by Volek, 2015 (5), may have been insuluin-resistant.

A Test.

A Test: Is there any athletes in the two groups who are insulin-resistant?

Post-prandial triglycerides in a low-carb self-experimenter.

Another factoid: Postprandial triglycerides triple after each meal in a low-carb self-experimenter. Is this self-experimenter metabolically healthy? Should he change his diet?

A factoid: Postprandial triglycerides triple after each meal in a low-carb self-experimenter.

Elevated nonfasting triglyceride levels in the general population.

Nordestgaard et al., 2007 (3):

We found that elevated nonfasting triglyceride levels, which indicate the presence of remnant lipoproteins, were associated with increased risk of MI, IHD, and total death in men and women in the general population.

The authors propose to explain the association of higher postprandial triglycerides with cardiovascular risk by the level of “remnant lipoprotein cholesterol”. The following citation also explains what the study population was. Nordestgaard et al., 2007 (3):

With increasing levels of nonfasting triglycerides, levels of remnant lipoprotein cholesterol increased (FIGURE 2). These levels were measured in 6677 of the original participants from the Copenhagen City Heart Study.

Figure 1.Triglyceride Levels and Levels of Remnant Lipoprotein Cholesterol as a Function of Time Since the Last Meal. Source: Nordestgaard et al., 2007 (3).

Figure 2.Levels of Remnant Lipoprotein Cholesterol as a Function of Levels of Nonfasting Triglycerides. Source: Nordestgaard et al., 2007.

Analysis: Among the general public, a lot more than elevated “Remnant Lipoprotein Cholesterol” may be wrong in the metabolism of subjects with elevated nonfasting triglycerides.

Conclusions.

In the general population, postprandial triglycerides appear to be associated with cardiovascular risk. In low-carb athletes and sedentary low-carbers, postprandial triglycerides rise to the same levels as those associated with higher cardiovascular risk in the general populattion. It is, however, not clear if higher postprandial triglycerides increase cardiovascular risk in people on low-carb diets.

Some claim that high amounts of fat consumed on low-carb high fat diets are safe and are really the best and the safest fuel. A larger question is whether this claim is true or whether it is always true.

A short summary.