"For a large proportion of the population, the effect of
higher-carbohydrate diets, particularly those enriched in refined
carbohydrates, coupled with the rising incidence of overweight and obesity,
creates a metabolic state that can favor a worsening of the atherogenic
dyslipidemia that is characterized by elevated triglycerides, reduced HDL
cholesterol, and increased concentrations of small, dense LDL particles."
- Siri-Tarino et al. 2010 (1)
“It was the opinion of some Cholesterol Conference
participants that recommendations based on attempts to isolate the effects of
dietary cholesterol from complex dietary patterns and extrapolations from
calculated models are flawed and may lead to unintended negative consequences.
It is, perhaps, more effective to recommend broader dietary patterns where
there is more direct evidence for an effect on health outcomes.” – Brownawell
and Falk 2010 (2)
Background
Cholesterol may be regarded as an "evil" dietary component, but
the fact remains that cholesterol is an essential molecule for human
development and bodily function. The critical role of cholesterol in
maintaining health is most evident in those suffering from genetic mutations
that result in the impairment of cholesterol synthesis; they suffer from
craniofacial abnormalities, syndactyly, polydactyly, genital malformations,
jaundice, and congenital heart disease (3).
Furthermore, cholesterol serves as the precursor for bile acids as well as many
hormones that we regard as invaluable for physical development such as
testosterone, estrogen, progesterone, as well as the adrenal hormones (4). Certainly there is a reason
that (dietary) cholesterol has become somewhat of a pariah - circulating blood
(serum) cholesterol levels are a good predictor of/reason for cardiovascular
disease.
More recently blood cholesterol has been described by the sort of protein
that it is associated with as it travels through our circulation in
cholesterol/protein complexes of various sizes. Thus when we talk about
LDL or HDL we are describing the entire circulating complex, rather than just
the total cholesterol found in circulation. Without going into the
mechanisms by which LDL or the LDL:HDL ratio or particle size contributes to
cardiovascular disease or metabolic syndrome, I think its safe to conclude that
high LDL levels in the blood in the absence of high HDL levels is associated
with unfavorable outcomes regarding our health.
Diet and Cholesterol
Consuming animal products, results in the consumption of dietary
cholesterol, plain and simple. Whether it be eggs, milk, cheese, or
steak, these contain some amount of cholesterol. Don't
make the common mistake to assume that all high fat foods contain
cholesterol; for example avocado, despite its buttery texture and plethora of
fats, avocado is a fruit, and cholesterol-free. Based on this
observation, one might conjecture that avoidance of animal products (i.e.
veganism) would facilitate tight regulation of serum cholesterol levels by
reducing all dietary cholesterol. Certainly from a dietary standpoint,
this is one very powerful way of eating that is beneficial for those
predisposed to be at a greater risk of cardiovascular disease (5).
Cholesterol also plays a hugely important role in the synthesis of bile
salts (bile) (4). These compounds are
synthesized in the liver, stored in the gall bladder, and secreted into the
intestine to help better absorb fats by emulsifying them and reducing
their hydrophobicity. Because bile is derived from cholesterol, one
dietary approach is to increase the amount of bile that is lost in the feces (6, 7).
Normally the body reabsorbs bile during digestion, but certain plant
components, mainly fiber, can bind bile and cause it to be lost in the stool (6). Thus, the body must
synthesize new bile from cholesterol, which is thought to help lower serum
cholesterol levels.
Regulation of Cholesterol Synthesis
Because of the critical importance of cholesterol in cell structure and
function, our bodies do not rely on dietary cholesterol as the sole source of
cholesterol. Perhaps even more important than dietary cholesterol,
endogenous cholesterol (cholesterol synthesized by our bodies) is a/the major contributor to
the total cholesterol pool within our bodies (4). The importance of
manipulating this pathway is emphasized by the methods for treating elevated
serum cholesterol in a clinical setting. One of the most commonly prescribed drugs
in for treating this condition is a family of drugs known as Statins (8).
Statins are HMG-CoA reductase inhibitors, an enzyme found mostly in the
liver responsible for the synthesis of cholesterol that is not obtained through
the diet (4). Inhibition of HMG-CoA
by Statins has been shown to lower serum cholesterol levels by nearly 50%,
supporting the notion that endogenously synthesized cholesterol makes up a
large portion of total serum cholesterol levels (8).
Follow me so far? HMG-CoA produces endogenous cholesterol.
 |
| Cholesterol Trafficking Pathways (Eatingacademy.com) |
Focusing on this pathway is of particular interest to me and leads me to ask
several questions. How does our body regulate cholesterol levels in the
absence of minimal dietary cholesterol? Does diet still influence this
pathway?
I guess the short-answer is yes, further investigation into this concept
reveals that dietary cholesterol travelling in cholesterol remnants such
as LDL or HDL reaching the liver results in feedback inhibition on HMG-CoA
reductase, such that, during a period of elevated dietary cholesterol, the body
receives a signal to reduce endogenous cholesterol synthesis (4). Feedback inhibition is
one mechanism that phytosterols, a plant component known to reduce circulating
cholesterol levels, are thought to work. Indeed, phytosterols have a very
similar structure to cholesterol, supporting the notion that feedback
inhibition results from phytosterols in the diet.
The concept of feedback inhibition results in the eventual question,
well then what happens when cholesterol is removed from the diet entirely?
Interestingly, in the absence of dietary cholesterol, endogenous cholesterol
levels can vary widely. In my understanding, serum cholesterol levels are
tightly related to endogenous synthesis rates i.e. HMG-CoA reductase activity (4), a high degree of which is
attributed to hormonal and genetic regulation of HMG-CoA reductase (9). Since genetic
regulation of HMG-CoA activity is more or less beyond our control at this time,
I'll talk about hormonal regulation of HMG-CoA activity. Especially and
specifically metabolic hormones such as insulin, glucagon, thyroid hormone, and
glucocorticoids.
The concept that insulin stimulates the liver to synthesize cholesterol was
first published as early as 1969 (as far as I could find). Interestingly,
in animals, complete absence of insulin signaling, HMG-CoA reductase levels are
nearly non-existent, suggesting a critical role for insulin in maintaining
basal cholesterol synthesis (10).
If insulin is a major driver of cholesterol synthesis, is there evidence
that dietary modifications independent of changing dietary cholesterol can
result in more promising outcomes regarding cholesterol and
cardiovascular health?
Evidence and Conjecture
I've spent a long time looking for specific studies that are well controlled
in regards to the relationship between serum cholesterol and glycemic load of
meals. While there may not be many studies designed to directly
examine this relationship from a mechanistic standpoint, there are a plethora
of dietary studies available that look at the correlations between study and
draw conclusions based upon.
In 2006 a group of scientists published a study in the Journal of Nutrition
that compared the effectiveness in reducing risk factors associated with cardiovascular
disease (mostly serum cholesterols). The authors chose to compare the
American Heart Association Diet (AHAD) and a Low Glycemic Index Diet (LGID)
containing plant phytosterols (11).
While both diets resulted in improved blood panels, the LGID diet was
more effective than the AHAD diet at improving blood panels when studying the
affect of the diets on serum cholesterol levels. Similar findings were
recently reported recently in two other separate occasions in women (12, 13),
and has also been reporte din men (14)
strongly supporting the notion that reducing glycemic load is associated with
reduced cardiovascular disease risk.
A direct opposite, a study looking at Japanese women found increasing the
glycemic load of the diet resulted in reduced HDL (15).
Because high HDL levels are considered protective, we again find a
situation in the literature where diets with a high glycemic load appear to
have negative impacts on the LDL:HDL ratio, one of the most important
biomarkers of risk. These are just some examples of numerous publications
looking at relationships between glycemic load (and thus insulin load) and
cholesterol levels. I should point out that there are other studies that
found no benefit to reducing glycemic index, although I'd argue the data seems
to generally support my position.
On
a side note: Do you think your doctor
knows about these studies and/or is aware of this sort of evidence????
Take Home Message(s).
I'm not going to go so far as to criticize carbohydrates, rather argue that
food choices should be made with glycemic index in mind. This is
especially important as food labels will use just about every catch phrase to
try to get you to buy the product. Just because you see a low-fat,
cholesterol free food, the glycemic index may be very high.
I don’t think this is a shocking concept to
anyone concerned with what they’re eating, however, I hope to have made a
relatively convincing argument here that dietary cholesterol is likely not a
major culprit in the ailing health of Americans. Because of the
aforementioned studies regarding the role of insulin and glycemic load in
regulating cholesterol synthesis, I feel confident saying that highly
insulinogenic diets, even in the absence of dietary cholesterol, have the
potential to be counter productive for persons watching cholesterol levels.
Eating
 |
| My idea of a pyramid |
I think the evidence presented here supports the importance of including
adequate fiber in the diet. (Soluble) Fiber has the potential to reduce
cholesterol levels through at least two mechanisms discussed here. #1
fiber lowers the glycemic index of a meal, thus reducing the amount of insulin
that will be secreted. #2 fiber also is capable of binding to bile,
causing it to be excreted, and forcing the body to use endogenous cholesterol
to synthesize new bile.
I could go on and on about what the food industry has done to us by creating
these "low-fat" foods, where sugar is relied on for taste rather than
fat. I'll try not to indict anyone, but I do think that fat the potential
to influence cholesterol levels in the diet, similar to fiber. Fat and protein
stimulate the secretion of bile through the production of CCK. Thus,
adequate fat is required in the diet to maintain or support bile secretion
during the consumption of a meal.
Furthermore, fat and protein also lower the glycemic load of a meal,
emphasizing the importance of having a diet adequately balanced in macro-nutrients.
Hmm what kind of diet is high in fiber, contains adequate fat and protein, and is generally low glycemic index and/or non-insulinogenic.
If you follow my blog, you probably know what
I’m thinking about already (cough, cough, paleo, cough, cough).
Works Cited
1. Siri-Tarino
PW, Sun Q, Hu FB, Krauss RM. Saturated fat, carbohydrate, and cardiovascular
disease. Am J Clin Nutr. Mar;91:502-9.
2. Brownawell
AM, Falk MC. Cholesterol: where science and public health policy intersect.
Nutr Rev. Jun;68:355-64.
3. Irons M,
Elias ER, Tint GS, Salen G, Frieden R, Buie TM, Ampola M. Abnormal cholesterol
metabolism in the Smith-Lemli-Opitz syndrome: report of clinical and
biochemical findings in four patients and treatment in one patient. Am J Med
Genet. 1994 May 1;50:347-52.
4. Ness GC,
Chambers CM. Feedback and hormonal regulation of hepatic
3-hydroxy-3-methylglutaryl coenzyme A reductase: the concept of cholesterol
buffering capacity. Proc Soc Exp Biol Med. 2000 May;224:8-19.
5. Craig WJ.
Health effects of vegan diets. Am J Clin Nutr. 2009 May;89:1627S-33S.
6. Lattimer JM,
Haub MD. Effects of dietary fiber and its components on metabolic health.
Nutrients. Dec;2:1266-89.
7. Story JA,
Furumoto EJ, Buhman KK. Dietary fiber and bile acid metabolism--an update. Adv
Exp Med Biol. 1997;427:259-66.
8. Nawrocki JW,
Weiss SR, Davidson MH, Sprecher DL, Schwartz SL, Lupien PJ, Jones PH, Haber HE,
Black DM. Reduction of LDL cholesterol by 25% to 60% in patients with primary
hypercholesterolemia by atorvastatin, a new HMG-CoA reductase inhibitor.
Arterioscler Thromb Vasc Biol. 1995 May;15:678-82.
9. Goedeke L,
Fernandez-Hernando C. Regulation of cholesterol homeostasis. Cell Mol Life
Sci. Mar;69:915-30.
10. Ness GC,
Wiggins L, Zhao Z. Insulin increases hepatic 3-hydroxy-methylglutaryl coenzyme
A reductase mRNA and immunoreactive protein levels in diabetic rats. Arch
Biochem Biophys. 1994 Feb 15;309:193-4.
11. Lukaczer D,
Liska DJ, Lerman RH, Darland G, Schiltz B, Tripp M, Bland JS. Effect of a low
glycemic index diet with soy protein and phytosterols on CVD risk factors in
postmenopausal women. Nutrition. 2006 Feb;22:104-13.
12. Shikany JM,
Tinker LF, Neuhouser ML, Ma Y, Patterson RE, Phillips LS, Liu S, Redden DT.
Association of glycemic load with cardiovascular disease risk factors: the
Women's Health Initiative Observational Study. Nutrition. Jun;26:641-7.
13. Jones JL,
Comperatore M, Barona J, Calle MC, Andersen C, McIntosh M, Najm W, Lerman RH,
Fernandez ML. A Mediterranean-style, low-glycemic-load diet decreases
atherogenic lipoproteins and reduces lipoprotein (a) and oxidized low-density
lipoprotein in women with metabolic syndrome. Metabolism. Mar;61:366-72.
14. Mosdol A,
Witte DR, Frost G, Marmot MG, Brunner EJ. Dietary glycemic index and glycemic
load are associated with high-density-lipoprotein cholesterol at baseline but
not with increased risk of diabetes in the Whitehall II study. Am J Clin Nutr.
2007 Oct;86:988-94.
15. Amano Y,
Kawakubo K, Lee JS, Tang AC, Sugiyama M, Mori K. Correlation between dietary
glycemic index and cardiovascular disease risk factors among Japanese women.
Eur J Clin Nutr. 2004 Nov;58:1472-8.
