Introduction
Postprandial lipemia (PPL), defined as the rise in circulating triacylglycerols (TAG)
following a meal, is an issue of concern to the medical community because it is
considered an independent risk factor for cardiovascular disease (CVD) [1]. Two non-pharmaceutical ways to lower PPL are
reducing fat intake and increasing exercise/physical activity; the latter
has been found to be more effective [2].
Postprandial TAG derive primarily from lipoproteins of intestinal (chylomicrons) and
hepatic origin (very low-density lipoproteins, VLDL). Circulating total, low-density
lipoprotein (LDL) and high-density lipoprotein (HDL) cholesterol concentrations are
barely influenced by normal food intake or after an oral fat load [3]
[4]. PPL is usually
measured through repeated blood sampling for 3 to 8 h after a meal and is
typically presented as TAG concentrations at the different sampling points, area
under the curve (AUC) or incremental AUC (iAUC), the latter being calculated by
subtracting the fasting concentration from postprandial concentrations.
The scientific literature concerning the effect of exercise on PPL displays a large
variety of study designs regarding (i) exercise type, intensity and duration, (ii)
meal content, (iii) timing of exercise relative to the test meal(s) and (iv)
characteristics of the participants. This makes it difficult to produce a clear
picture of the effect of exercise on PPL. Nevertheless, previous reviews on both
healthy and diseased individuals have concluded that exercise has an acute, moderate
lowering effect on PPL, with a positive influence of the energy expenditure of
endurance exercise [5]
[6]
[7]
[8]
[9]
[10]
[11]
[12]
[13].
The aim of this review is to present an update covering the effect of exercise on
PPL. We will discuss why exercise is important, when it is more
effective to exercise relative to a meal, what is the preferred exercise and
how exercise lowers PPL.
Criteria for study inclusion
The review was mainly based on a PubMed search for studies including one of the
terms, “exercise,” “physical activity” and
“exercise training,” and one of the terms, “postprandial
lipemia,” “postprandial triacylglycerol” and
“postprandial triglycerides,” published from 2014 to present
(unless our reference to earlier studies served a specific purpose or a
reference was not included in previous reviews), as the detailed reviews by
Maraki and Sidossis [8] and Freese and coworkers
[10] cover the issue up to 2014. Additional
studies were found through the reference lists of some studies. To be included
in the review, studies had to be on humans, with adequate description of the
exercise and test meals used, with at least 3 h of postprandial TAG
measurements, with a no-exercise control and written in English.
Why is exercise important in lowering PPL?
The answer to this question lies in the following:
-
Most individuals are in a postprandial state during the largest part of
the time they are awake, as they usually consume two to three main meals
and intermediate snacks during the day. Additionally, dietary patterns
characterized by high consumption of fat and carbohydrate, which prevail
in many modern societies, lead to high PPL [4]
[14].
-
PPL plays a crucial role in the formation and development of
atherosclerosis, mainly through endothelial dysfunction, oxidative
stress and inflammation; this makes PPL an independent risk factor for
CVD [1]. Specifically, PPL is connected to
atherogenicity through the remnants of postprandial lipoproteins, which
infiltrate the arterial wall, leading to the accumulation of
atherosclerotic plaques, and through changes in HDL and LDL (decreased
HDL cholesterol and increased small-dense LDL particles) [5]. Epidemiological studies have found that
an increase of 1 mmol/L (88.5 mg/dL) or
higher in non-fasting, or postprandial, circulating TAG concentration is
associated with increased risk, ranging from 1.2 to 16.8-fold, of CVD
and death [15]
[16]. Additionally, an increase of 1 mmol/L
(39 mg/dL) in plasma non-fasting remnant cholesterol (a
marker of which is postprandial TAG) is associated with a 2.8-fold
causal risk for ischemic heart disease [17].
Attesting to the deleterious effects of PPL, a panel of experts [18] and the European Atherosclerosis
Society and European Federation of Clinical Chemistry and Laboratory
Medicine [19] have recommended the
replacement of fasting by non-fasting plasma TAG concentration in the
assessment of CVD risk, with a non-fasting concentration
of≥220 mg/dL
(≥2.50 mmol/L) indicating increased CVD risk
[18]. It has been suggested that
individuals with fasting TAG<70 mg/dL will
likely not exceed postprandial TAG of 220 mg/dL and
individuals with fasting TAG>130 mg/dL will
likely exceed postprandial TAG of 220 mg/dL, whereas
individuals with fasting TAG between 70 and 130 mg/dL
should be recommended for postprandial TAG testing [20]. Thus, decreasing postprandial lipid
concentrations could be a measure against CVD.
-
Exercise lowers PPL, as has been concluded by reviews [8]
[10] and
will be further shown in the present update, although the clinical
relevance of this effect is limited. To document this, we examined how
many of the original studies that are included in the present review and
showed a significant effect of exercise on PPL satisfied the criterion
of lowering circulating TAG by at least 1 mmo/L, which
is the minimal established clinically relevant effect [15]
[16]. On
this basis, 7 studies demonstrated a clinically relevant effect, with an
average TAG reduction of 38% (range 29 to 47%) [21]
[22]
[23]
[24]
[25]
[26]
[27], whereas 42 studies did not find a
clinically relevant effect, with an average TAG reduction of 22%
(range 4 to 35%) [14]
[28]
[29]
[30]
[31]
[32]
[33]
[34]
[35]
[36]
[37]
[38]
[39]
[40]
[41]
[42]
[43]
[44]
[45]
[46]
[47]
[48]
[49]
[50]
[51]
[52]
[53]
[54]
[55]
[56]
[57]
[58]
[59]
[60]
[61]
[62]
[63]
[64]
[65]
[66]
[67]
[68].
-
In addition to its postprandial TAG lowering effect, exercise plays an
important role in improving inflammation [69], reducing oxidative stress [39], and protecting the vasculature from the deleterious
effects of a high-fat meal [70]
[71]
[72],
although evidence for a lack of such effects also exists [73]
[74]
[75].
Thus, the short answer to the title question (why is exercise important in
lowering PPL?) is: Exercise lowers PPL, which characterizes large parts of the
day and is an independent risk factor for CVD.
When is it most effective to exercise to lower PPL?
To facilitate the examination of this question, we have grouped studies according
to the timing of exercise relative to the test meal(s) and according to the fat
content of the test meal(s). Moreover, we consider the chronic effect of
exercise (that is, training) on PPL.
Exercise performed on the day preceding a high-fat meal
Since 2014, 36 studies have confirmed that exercise performed on the evening
prior to a morning high-fat meal (that is, a meal containing above 0.7 g of
fat per kg body mass) lowers PPL, compared to no exercise. This has been
shown in young, middle-aged and/or older men [14]
[21]
[22]
[23]
[27]
[28]
[29]
[30]
[31]
[32]
[33]
[34]
[35]
[36]
[37]
[38]
[39]
[40]
[41]
[42]
[43]
[76]
[77], young men and women [44], young or middle-aged women [45]
[67], normal
and overweight individuals [68], overweight
and obese individuals [24]
[46]
[47] and
adolescent boys and girls [48]
[49]
[50]
[51]
[52]
[53].
On the other side, 13 studies have reported no significant effect on PPL when
exercise was performed on the evening preceding a morning high-fat meal.
Specifically, this has been shown in men [39]
[70]
[78]
[79]
[80]
[81]
[82], older adults [79]
[83], postmenopausal women [84], overweight and obese individuals [73]
[85] and
adolescent boys and girls [86]
[87]. It is worth mentioning that there is a
great diversity of types of exercise performed in these studies.
A possible explanation for not finding a lowering effect of exercise on PPL
is the compensation for the energy expenditure of exercise through a meal
[73]. Immediate replenishment of the
exercise-induced energy deficit diminished the reduction in PPL [43]
[64]
[88]. Along the same line, previous studies have
shown that maintaining an exercise-induced energy deficit resulted in a
greater reduction in TAG iAUC, compared to restoring energy balance through
food intake [10], although previous data
demonstrated greater reduction of PPL with exercise compared to equivalent
dietary energy deficit [89]. A factor that may
modulate the role of compensation for the energy expenditure of exercise
through a postexercise meal is its carbohydrate content, as a
low-carbohydrate meal did not diminish the lowering effect of exercise on
PPL, whereas an isoenergetic high-carbohydrate meal did [27]. In overweight and obese individuals,
consumption of low-glycemic index carbohydrates after exercise did not
diminish the attenuation of PPL, whereas consumption of high-glycemic index
carbohydrates did, which was attributed to the suppression of fat oxidation
by the higher insulin response to the high-glycemic index meal [24]. Nevertheless, replenishment of the
exercise energy expenditure by glucose did not affect the exercise-induced
decrease in PPL, possibly because of an absence of an effect on the insulin
response [21].
Habitual physical activity may be a determinant of the effect of acute
exercise on PPL, since recent studies have shown that exercise performed on
the evening prior to a high-fat meal failed to reduce PPL when daily step
count was low (< 5000 steps) and/or sitting time was long,
as opposed to high daily step count (8500 steps) [90]
[91]
[92]. This effect has been termed “exercise
resistance” [92].
Exercise performed on the day preceding a moderate-fat meal
A few studies examining the effect of exercise on PPL have used test meals of
moderate fat content (that is, 0.4 to 0.7 g of fat per kg body mass)
to be closer to real-life settings. All support a lowering effect of
exercise, performed approximately 12 h before the test meal, on PPL
compared to no exercise. This has been shown in adults [54]
[55],
postmenopausal women [56]
[57] and adolescent boys [58].
Exercise performed on the day of a high- or moderate-fat meal
Many studies have examined the effect of exercise on PPL when exercise is
performed on the same day as the test meal. This includes the following
cases: (i) exercise before the test meal, (ii) exercise after the test meal
and (iii) exercise both before and after the test meal.
Most of the studies that employed exercise immediately to 1 h before
a high-fat meal found no effect on PPL in lean and obese men [93]
[94], trained
men [95]
[96],
hypercholesterolemic individuals [59]
[97] and adolescents [60]
[71]. This was also the case
with low/moderate-fat meals in obese adults [98]
[99] and individuals with
chronic paraplegia [100].
In contrast, there are studies that have reported a lowering effect of
exercise, performed 30 min to 1 h before a high-fat meal, on
PPL in adults [25]
[59] and girls [60]. A lowering
effect was also found when exercise was performed 2 h before a
high-fat meal in overweight and obese men [61]
and in postmenopausal women [26], as well as
4.5 h before a high-fat meal in men with prediabetes [62]. Interestingly, a pre-exercise fructose
drink (low glycemic index) resulted in lower PPL after a high-fat meal that
was administered immediately after exercise, as compared to a pre-exercise
glucose drink (high glycemic index) [101].
Another study design, closer to real-life conditions, involves short bouts of
exercise that interrupt prolonged sitting (with or without comparison to
continuous exercise), performed between two or three meals (breakfast, lunch
and dinner) during the day. A variety of exercise types and timing patterns
have been used. A recent meta-analysis found that regular activity breaks
from prolonged sitting (“exercise snacks”) did not change
PPL when compared to prolonged sitting [102].
A subsequent meta-analysis reported a small effect of breaking up sitting
with physical activity on attenuating PPL, whereas there was no difference
between exercise snacks and a bout of continuous exercise [103]. Both meta-analyses showed that exercise
snacks were more effective in lowering PPL when performed the day before the
test meal [102]
[103].
Results from original studies following (or not included in) the
aforementioned meta-analyses are similar. Breaking up prolonged sitting with
standing, walking, chair squats, resistance exercise (RE) or stair climbing
in young healthy individuals [104]
[105]
[106],
individuals with increased cardiometabolic risk [106]
[107]
[108]
[109]
[110] and older women [109] on the
day of the test meals did not affect PPL.
However, there are data supporting reduced PPL by frequent interruptions of
prolonged sitting with light- and moderate-intensity walking breaks in young
obese men [63] and postmenopausal women [26]. Additionally, accumulating short bouts of
brisk walking throughout the day reduced PPL in older women, although
dietary replenishment of the exercise-induced energy deficit diminished this
effect [64]. Finally, PPL was reduced by a
combination of moderate-intensity continuous exercise (MICE) and exercise
snacks, relative to uninterrupted sitting, in men and postmenopausal women
over 55 y, suggesting an additive effect [65].
Exercise performed after a high- or moderate-fat meal
Many people exercise in the postprandial, rather than postabsorptive, state,
as modern lifestyles include a large number of meals and snacks during the
day. Reviews have concluded that, although post-meal exercise is more
beneficial than pre-meal exercise in lowering postprandial hyperglycemia in
healthy individuals and individuals with type 2 diabetes [111]
[112],
pre-meal exercise is superior to post-meal exercise in lowering PPL [111].
In accordance with this conclusion, no difference in PPL was found between
walking immediately to 1 h after a high-fat or Mediterranean-diet
meal and resting [74]
[113]
[114]. Curiously, exercise
split between the early pre- and postprandial periods resulted in a higher
lipemic response, compared to no exercise [94]. On the contrary, RE performed 2 h after a high-fat meal
attenuated PPL and improved peripheral arterial stiffness [115]. Additionally, combined walking and light
RE performed 1 h after a high-fat meal attenuated PPL and,
interestingly, more so compared to the same exercise performed 1 h
pre-meal [66].
Exercise training
Findings show that the effect of exercise on PPL is an acute one [7], in contrast to its well-established chronic
effect on fasting TAG concentration [116].
While endurance-trained people generally have low PPL and rapid TAG
clearance, this is quickly reversed in the absence of recent exercise [5]. Data from the last decade confirm that the
attenuating effect on PPL is abolished 37 to 48 h after an exercise
session [14]
[34]
[117]. Therefore, any effect of
exercise training on PPL should be considered a chronic effect only if it is
observed at least two days after the last exercise session. In this sense,
findings of studies that investigated the effect of training on PPL by
administering a test meal less than two days or on undisclosed time after
the last exercise session [118]
[119]
[120]
[121]
[122] cannot
be considered as reflecting chronic exercise effects.
No effect of training on PPL was found after four weeks of high-intensity
interval training in healthy volunteers when the test meal was administered
at least three days after the last exercise session [123]. Similarly, eight weeks of low-volume endurance training did
not influence PPL two days after the last session [124]. Additionally, no difference in PPL one day after the last
session was observed between physically active and inactive patients with
CVD [125]. Finally, there does not appear to
exist an additive effect of previous exercise sessions, performed on
consecutive days, to that of the last session [41]
[67]
[126]. On the other hand, two studies that compared the
postprandial TAG response to a high-fat meal between inactive adults and
physically active adults, who had abstained from exercise for two days,
reported lower PPL in the active groups [127]
[128]. Overall, it is
interesting to mention that most studies that focused on the effects of
training found a decrease in baseline TAG, which by itself is fairly
interesting in terms of cardiovascular risk.
Thus, the short answer to the title question of this section (when is it most
effective to exercise to lower PPL?) is: Exercise lowers PPL most
effectively when it is performed on the day preceding a high- or
moderate-fat meal, and this effect lasts up to approximately two days.
What is the preferred exercise to lower PPL?
The types of exercise examined in previous reviews include MICE, HIIE, RE and
accumulating exercise in the form of several short bouts throughout the day
[8]
[9]
[10]
[11]
[129]. Below we review recent findings on this
issue, as summarized in [Table 1].
Table 1 Numbers of studies on the effects of exercise on
postprandial lipemia published from 2014 to present.
|
Type of exercise
|
Timing of exercise relative to the test meal
|
Effect
|
Percentage of studies showing a lowering effect
|
|
|
Lowering
|
None
|
|
|
Moderate-intensity continuous exercise
|
Previous day
|
19
|
8
|
70
|
|
Same day
|
4
|
8
|
33
|
|
High-intensity interval exercise
|
Previous day
|
8
|
4
|
67
|
|
Same day
|
2
|
1
|
67
|
|
Resistance exercise
|
Previous day
|
3
|
2
|
60
|
|
Same day
|
1
|
1
|
50
|
|
Accumulating short bouts of exercise
|
Previous day
|
3
|
0
|
100
|
|
Same day
|
3
|
7
|
30
|
MICE
Walking, running or cycling for 30 to 90 min at intensities ranging
from 45 to 70% of VO2peak reduced PPL when performed
on
-
the day before a high-fat meal [14]
[21]
[28]
[29]
[33]
[36]
[39]
[40]
[42]
[46]
[49]
[50]
[53]
[76]
[77],
-
the day before a moderate-fat meal [54]
[55]
[57]
[58]
or
-
the day of a high-fat meal [25]
[60]
[61]
and a moderate-fat meal [26].
On the contrary, there are studies showing no effect of MICE on PPL when
performed on
-
the day before a high-fat meal [23]
[37]
[73]
[78]
[79]
[81]
[83]
[85],
-
the day of a high-fat meal [71]
[93]
[95]
[96]
[97] or
-
the day of a moderate-fat meal [60]
[98]
[99].
In addition, a study has found reduced PPL with MICE in metabolically healthy
individuals but not in individuals with metabolic syndrome [59]. Regarding the issue of whether MICE
intensity plays a role in the lowering of PPL, most findings show a positive
association [10], although, in one study [38], both high- and moderate-intensity
exercises of similar energy expenditure were found to reduce PPL without a
difference between intensities.
HIIE
From data reviewed in 2015, it appears that supramaximal, low-volume HIIE can
induce reductions in PPL, but findings are inconsistent [11]. On the contrary, all studies using
submaximal, high-volume interval exercise showed reductions in PPL [11]. Studies published afterwards showed that
HIIE in the form of running or cycling reduced PPL when performed on
-
the day before a high-fat meal [22]
[23]
[37]
[47]
[48]
[51]
[52],
-
the day before a moderate-fat meal [58]
or
-
the day of a high fat meal [60]
[61].
On the contrary, there are studies showing no significant effect of HIIE on
PPL when performed on
Comparisons between HIIE and MICE have shown the former to be more effective
in lowering PPL, even when it has a lower energy expenditure [10]
[23]
[37]. However, low-intensity intermittent
exercise was less effective than MICE [130],
suggesting that exercise intensity is more important than exercise mode in
lowering PPL.
RE
Recent studies have shown mixed results regarding the effect of RE on PPL,
since some have found a lowering effect when exercise was performed on the
day before [35]
[39]
[43] or on the day of the test
meal [62], while others did not find a
lowering effect when exercise was performed on the day before [82]
[84] or on the
day of the test meal [98]. Additionally,
combined strength and endurance exercise of either circuit (strength
exercises alternated with running bouts) or traditional pattern (strength
exercises followed by MICE) reduced PPL after a high-fat meal [32].
Accumulating short bouts of exercise throughout the day
Performing short bouts of exercise during the day provides an additional
physical activity option to individuals with limited time or with limited
capacity to engage in more structured forms of exercise [9]. Most of the evidence until 2013 [9] and afterwards [30]
[56] shows that exercise
accumulated in this way is as effective as continuous exercise in reducing
PPL on the next day. This has also been found with cycling sprints spread
over the day [44]. When short bouts of
exercise are performed on the day of the meal(s), most studies find no
effect on PPL [104]
[105]
[106]
[107]
[108]
[109]
[110], whereas some find a
lowering effect [26]
[63]
[64].
Thus, the short answer to the title question of this section (what is the
preferred exercise to lower PPL?) is: Although MICE, HIIE, RE and
accumulating short bouts of exercise throughout the day are all effective in
lowering PPL, submaximal, high-volume interval exercise seems to be
superior.
How does exercise reduce PPL?
The potential factors contributing to the reduction of PPL by exercise are a
lower rate of appearance and a higher clearance of TAG-rich lipoproteins (that
is, intestinally derived chylomicrons and hepatically derived VLDL) during the
postprandial period. Let us consider the evidence.
Lower rate of appearance of TAG-rich lipoproteins in the
circulation
Exercise may lower the rate of appearance of TAG-rich lipoproteins in the
circulation due to
-
decreased VLDL secretion [8]
[10],
-
decreased rate of appearance of chylomicrons [12] and
-
decreased incorporation of endogenous and meal-derived fatty acids
into TAG-rich lipoproteins [62].
Higher clearance of TAG-rich lipoproteins from the circulation
After a meal, chylomicrons compete with VLDL for clearance by lipoprotein
lipase (LPL) residing on the capillary endothelium of extrahepatic tissues,
particularly adipose tissue and skeletal muscle. Exercise possibly augments
this process through
-
increased whole-body postprandial fatty acid oxidation [2]
[12]
[30], which may create a
steeper inward fatty acid gradient, thus augmenting TAG hydrolysis
by LPL,
-
increased expression of the muscle LPL gene during
4–8 h post-exercise, which returns to baseline at
about 20 h [131], thus fitting
with the time frame of the effectiveness of exercise in reducing
PPL,
-
increased muscle LPL activity [12],
-
increased affinity of large VLDL particles for LPL postprandially
[46] and
-
increased chylomicron clearance because of decreased VLDL secretion
and, hence, lower competition for LPL [132].
The reader is referred to Figure 2 of Gill and Hardman [5] for a visual presentation of the potential
mechanisms involved. It is possible that the contribution of each of the
aforementioned mechanisms to the PPL-lowering effect of exercise differs
according to the time between exercise and meal, as well as the type of
exercise. Thus, because activation of muscle LPL peaks at about 8 to
18 h post-exercise [131]
[133], this is probably the main mechanism of
PPL reduction in studies in which exercise was performed on the day
preceding the meal, whereas decreased VLDL secretion is probably the main
cause of PPL reduction when exercise precedes the meal by fewer than
3 h [132]. Additionally, studies using
MICE suggest that reduced VLDL secretion may be more important than
increased LPL activity and/or mass in PPL reduction [134], whereas evidence suggests that HIIE
elicits PPL reduction mainly by increasing skeletal muscle LPL activity
and/or mass [11]
[135].
Thus, the short answer to the title question of this section (how does
exercise reduce PPL?) is: Exercise reduces PPL by both lowering the rate of
appearance and increasing the clearance of TAG-rich lipoproteins from the
circulation.
