Saturated Fat, Cholesterol & Carbohydrates all over the World & Updates

Hello again! It’s been a long 5 months since TheFatNurse’s last post! I’ve been finishing up the last semester of my Family Nurse Practitioner Program and getting ready for the Boards. This means I’ve been spending less time focusing on fat related issues and more time diving into other areas of health. As result, I’ve had less time to focus on the blog. I do plan to get back into updating more regularly once the year is over.

However, the past couple of weeks has had several developments that are too note worthy to not mention! Starting in Australia:

ABC has an investigative show called Catalyst in Australia. Last week they aired a controversial report on saturated fat and cholesterol’s weak association with heart disease. This generated the obvious controversy…but the show followed it up with an episode about statins that generated even more controversy!

The basic premise of this episode was the overprescription of statins based off faulty guidelines and research on primary prevention groups (this is important to keep in mind). In addition to the literature on statins and heart disease, the show also covers some of the research process/designs when drug trials are conducted that can lead to flawed conclusions.

The expected controversy even lead the Australian Advisory Committee to urge ABC to pull the episode from airing since they believed it could have lead people to stop taking their medications – leading to death. Today Dr. Kerryn Phelps, a former Australian Medical Association president, added to the controversy by writing:

Screen Shot 2013-11-01 at 12.33.06 PM

Both episodes are worth a look to understand what the discussion is all about as many people are probably going to be confused with all this conflicting advice.

Moving onto Italy:

Apparently Pasta consumption has dropped 23% in the past decade. Why is this?

Worried about its fattening effects, she and her husband eat it no more than a few times a week, favoring couscous, meat and vegetables instead. “Metabolism changes when you approach 40,” she says, “and pasta is out of the question.”

The share of women between 26 and 30 years old who believe pasta is fattening increased 26% from 2008 to 2012, according to a Nielsen survey. And among 26- to 30-year-old men, the number who think pasta makes people fat increased 16%.

Reminds me of this episode of Portlandia:

Now to Britain:

Looks like the amount of saturated fat that will be in Britain will be decreased and taken out of the food supply:

Almost half of the food manufacturing and retail industry has signed up to the Responsibility Deal Saturated Fat Reduction Pledge by agreeing to reduce the amount of saturated fat in our food and change their products to make them healthier.

Cutting the amount of saturated fat we eat by just fifteen per cent could prevent around 2,600 premature deaths every year from conditions such as cardiovascular disease, heart diseaseand stroke.

Check out the link to the story which details what companies are planning to do. Such as:

Nestlé – which will remove 3,800 tonnes of saturated fat from over a billion Kit Kat bars per year by reformulating the recipe

And whatever they end up replacing the saturated fat will make kit kats “healthier?” Sigh…

And in Sweden:

Apparently, “Sweden has become the first Western nation to develop national dietary guidelines that reject the popular low-fat diet dogma in favor of  low-carb high-fat nutrition advice.”

I’ve heard in the past that a huge portion of the population in Sweden follows a Low Carb High Fat diet so this is not too surprising.

We’ll end with China

I’ve covered in the past how asians are often used in popular press to demonstrate how carbohydrates cannot be fattening since Asians are so skinny…despite being healthy and skinny not being the same thing.

Apparently a new study was released last month showing increased carbohydrate consumption being tied to coronary heart disease in the Chinese.

I won’t get into too much about this particular study since it’s observational and relies on questionnaires – which have faults in generating conclusive evidence. However, these study designs were used in the past to demonize dietary fat. So even if this study is not conclusive, it’s worth noting since it produced different results using similar methods in the past. Some notable observations:

These associations were robust and independent of several known CHD risk factors, including socio economic status, centralobesity, smokingstatus, hypertension, and saturated fat intake.

In a Japanese cohort, the average intakes of raw white rice were 170 g/day in women and 180 g/day in men. In that study, white rice intake was found to be inversely associated with death from cardiovascular disease in men but not in women (49). The reasons for the apparent conflicting results between that study and ours are not clear.

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Lipids: What School Did and Did Not Teach

Hello again world! It’s been a long two months since TheFatNurse last posted due to busy events in TheFatNurse’s life. However, since that time, TheFatNurse finally had the lecture on lipids and heart disease in TheFatNurse’s nursing school. It had it’s highs, lows and also a few surprises as well. This post should offer you some insights into some of the formal education that some health care professionals may receive regarding lipids.

 Cholesterol is the most highly decorated small molecule in biology. Thirteen Nobel Prizes have been awarded to scientists who devoted major parts of their careers to cholesterol. Ever since it was isolated from gallstones in 1784, cholesterol has exerted an almost hypnotic fascination for scientists from the most diverse areas of science and medicine…

 -Michael Brown and Joseph Goldstein Nobel Lectures (1985)

I. Going Over The Basics

The lecture began with a quick overview of lipids. Specifically, the instructor explained that cholesterol was “made in the liver” and “absorbed in the gut.” This is only somewhat true; while the liver is most known for cholesterol synthesis, cholesterol is also made de novo in extrahepatic cells (made outside the liver) where it is often trafficked in pathways that cross/involve the liver.

The instructor also commented about cholesterol being absorbed in the gut…but did not make it clear where that cholesterol came from and could make one think he was referring to dietary cholesterol. However, most of the cholesterol that is absorbed in our gut is actually biliary in origin rather than diet.

TheFatNurse has gone over the basics of lipid metabolism in previous posts so won’t go over it again too much in this post but if you need a quick refresher a good review of the subject matter can be found here in this review in Nature [1]

Not everyone has an academic journal account so you can also gleam most of the basics of cholesterol in these two comics from the TheFatNurse comic collection

Cover

Click here for a review about the history of lipoproteins & cholesterol!

Click here for a review on what HDL and Triglycerides Do!

Click here for a review on what HDL and Triglycerides Do!

If you’re craving more in depth details then I would highly recommend reading Dr. Dayspring’s “Lipid and Lipoprotein Basics” [2] which contains not only a comprehensive overview of all the dynamic relationships involving everything lipid but also helpful diagrams that help visualize the whole process.

The instructor then proceeded to mentioned particles and explained, “cholesterol is found in HDLs, LDLs and IDLs.” This is somewhat correct, but cholesterol is also carried by Chylomicrons and VLDLs (although both to a lesser degree). The instructor also went over triglycerides and informed the class that they could be used for energy but were associated with higher cardiovascular risk and were carried by Chlyomicrons and VLDLs. Again, this is only somewhat true, since triglycerides can be found in HDLs, LDLs, and IDLs as well. This is important because the variations in how much triglycerides these lipoproteins have is associated with many dynamic changes on how many lipoproteins you have, their sizes, and ultimately even your cardiovascular risk. You can see a breakdown of their percentages of cholesterol and triglycerides below:

LP-Density-Wiki

The biggest critique TheFatNurse had with the intructors’ explanation of cholesterol was the lack of separation in explaining the differences between lipoproteins and cholesterol. For example, the instructor would mention “LDL cholesterol” and “HDL cholesterol” various times as if these were two different types of cholesterol. Cholesterol is cholesterol and it’s either in an unesterified form or esterified form. When we mention measurements of “HDL-cholesterol” or “LDL-cholesterol” we are hoping that the cholesterol we find on these lipoproteins tells us how many lipoproteins there are. This confusing language was mentioned in Frederickson, Levy and Lee’s landmark 5-part series on lipids in The New England Journal of Medicine [3] back in the 60’s.

Even then, Fredrickson, Levy and Lees pointed out that it may be more appropriate to use the terms dyslipoproteinemia and hyperlipoproteinemia rather than dyslipidemia and hyperlipidemia since the focus was on the lipoproteins rather than the lipids themselves. The lack of using this terminology in today’s world can be attributed to much of the confusion about cholesterol and lipoproteins in general (If there is still some confusion, there’s some pictures that provide an analogy of cholesterol vs the lipoproteins further down this post as well as more clarification in the cholesterol comics posted earlier).

II. Going Over Clinical Lipid Values

The instructor then informed the class that we could get these measurements through a fasting lipid panel to evaluate the total cholesterol and LDL cholesterol which would inform us of our risk and give us a target to shoot for. This created a transition to introduce the ATP-III guidelines [4] for us. However, at this point TheFatNurse put up a raised hand to point out the importance of how elevated triglycerides can effect the estimation of LDL-cholesterol (calculated by the Friedewald equation). [5] The ATP-III guidelines are old and definitely has problems, but what was disturbing was the lack of any mention on looking at non-HDL cholesterol which is actually mentioned in the guidelines!

Many persons with atherogenic dyslipidemia have high triglycerides
(≥200 mg/dL). Such persons usually have an increase
in atherogenic VLDL remnants, which can be estimated clinically by measuring VLDL cholesterol. In persons with high triglycerides, the combination of LDL cholesterol + VLDL cholesterol (non-HDL cholesterol) represents atherogenic cholesterol. Non-HDL cholesterol thus represents a secondary target of therapy (after LDL cholesterol) when triglycerides are elevated.

YUNONONHDL

Indeed, Non-HDL-Cholesterol  (Total Cholesterol – HDL-Cholesterol) is often a better predictor of risk than LDL-cholesterol. A simple search through pubmed will provide you with all sorts of studies for different populations. Here’s a small sample:

“Non-HDL cholesterol and apoB are more potent predictors of CVD incidence among diabetic men than LDL cholesterol” [6]

“Non-HDL-C was more strongly associated with subclinical atherosclerosis than all other conventional lipid values. These data suggests that Non-HDL-C may be an important treatment target in primary prevention.” [7]

“We reconfirmed non-HDL-C as a predictor of the risk for CAD and a residual risk marker of CAD after LDL-C-lowering therapy” [8]

“For participants with triglycerides <2.26 mmol/L (<200 mg/dL), the overall misclassification rate for the CVD risk score ranged from 5% to 17% for cLDL-C methods and 8% to 26% for dLDL-C methods when compared to the RMP…For participants with triglycerides ≥2.26 mmol/L (≥200 mg/dL) and <4.52 mmol/L (<400 mg/dL), dLDL-C methods, in general, performed better than cLDL-C methods, and non-HDL-C methods showed better correspondence to the RMP for CVD risk score than either dLDL-C or cLDL-C methods.” [9]

“The discrimination power of non-HDL-C is similar to that of apoB to rank diabetic patients according to atherogenic cholesterol and lipoprotein burden. Since true correlation between variables reached unity, non- HDL-C may provide not only a metabolic surrogate but also a candidate biometrical equivalent to apoB, as non- HDL-C calculation is readily available.” [10]

“…among statin-treated patients, levels of LDL-C, non–HDL-C, and apoB were each strongly associated with the risk of major cardiovascular events, but non–HDL-C was more strongly associated than LDL-C and apoB. Given the fact that many other arguments for the clinical applicability of non–HDL-C and LDL-C are identical, non–HDL-C may be a more appropriate target for statin therapy than LDL-C.” [11]

“CHD risk associated with ↓HDL-C in women was >2- to 4-fold elevated depending on TG levels. Non-HDL cholesterol was a significant predictor of CHD in men.” [12] *of note this study reported findings that “Non-HDL cholesterol was significantly related to CHD in men but not in women.”

“non-HDL-C remains an important target of therapy for patients with elevated TGs, although its widespread adoption has yet to gain a foothold among health care professionals treating patients with dyslipidemia.” [13]

“…in a Dutch population-based cohort…Both men and women with increasing levels of apoB and non-HDL-c were more obese, had higher blood pressure and fasting glucose levels, and a more atherogenic lipid profile….data support the use of first apoB and secondly non-HDL-c above LDL-c for identifying individuals from the general population with a compromised CV phenotype.” [14]

“Future guidelines should emphasize the importance of non–HDL-C for guiding cardiovascular prevention strategies with an increased need to have non–HDL-C reported on routine lipid panels.” [15]

There was honestly a lot more out there so TheFatNurse thought it was a little disturbing that the only lipid parameter that was covered was Total Cholesterol and LDL-Cholesterol, especially since Non-HDL (unlike Apo-B, LDL-particle count or Lipoprotein sizes) does not require advance lipid testing and is readily available with some simple math on a basic lipid panel.

Another free lipid marker that was not covered is the Triglyceride/HDL ratio. Again, there is plenty of evidence suggesting that this ratio should be evaluated due to it’s predictive value for metabolic syndrome which increases one’s cardiovascular risk significantly. Metabolic syndrome is elevated BP, increased trunk obesity, elevated triglycerides, decreased HDL, and impaired fasting glucose. You need 3 out of the 5 for the official diagnosis:

“The Tg/HDL-C ratio could be a useful index in identifying children at risk for dyslipidemia, hypertension, and MS.” [16]

“Among women with suspected ischemia, the TG/HDL-C ratio is a powerful independent predictor of all-cause mortality and cardiovascular events.” [17]

“We evaluated the predictive value of a surrogate maker of insulin resistance, the ratio of triglyceride (TG) to high-density lipoprotein (HDL), for the incidence of a first coronary event in men workers according to body mass index (BMI)… In conclusion, the TG/HDL ratio has a high predictive value of a first coronary event regardless of BMI.” [18]

“A triglyceride/HDL cholesterol ratio of 3.8 divided the distribution of LDL phenotypes with 79% (95% confidence interval [CI] 74 to 83) of phenotype B [more atherogenic] greater than and 81% (95% CI 77 to 85) of phenotype A less than the ratio of 3.8. The ratio was reliable for identifying LDL phenotype B in men and women.” [19]

“…results add further support to the notion that the TG/HDL-C ratio may be a clinically simple and useful indicator for hyperinsulinemia among nondiabetic adults regardless of race/ethnicity.” [20] *of note, there is some research suggesting that the TG/HDL marker may not be as good of a predictive marker for insulin resistance for African-American women in other studies.

“The triglyceride/HDL ratio, a simple, readily available and inexpensive measure, can be a useful surrogate to identify those with insulin resistance as well as those with more atherogenic small LDL particles in nondiabetic patients with schizophrenia.” [21]

“…findings of this study demonstrate that the triglyceride-to-HDL cholesterol ratio is associated with insulin resistance measures in White Europeans and South Asian men; this relationship appeared to be less established in South Asian women.” [22]

“The TG/HDL-C ratio may be a good marker to identify insulin-resistant individuals of Aboriginal, Chinese, and European, but not South Asian, origin.” [23]

“An elevated TG/HDL-C ratio appears to be just as effective as the MetS diagnosis in predicting the development of CVD.” [24]

“Adolescents with an elevated TG/HDL ratio are prone to express a proatherogenic lipid profile in adulthood. This profile is additionally worsened by weight gain.” [25]

“The TG/HDL-C ratio is associated with IR mainly in white obese boys and girls and thus may be used with other risk factors to identify subjects at increased risk of IR-driven morbidity.” [26]

The importance of predicting insulin resistance is  associated with it’s impact on the lipoprotein profile and thus cardiovascular risk:

“…progressive insulin resistance was associated with an increase in VLDL size (r = −0.40) and an increase in large VLDL particle concentrations (r= −0.42), a decrease in LDL size (r = 0.42) as a result of a marked increase in small LDL particles (r = −0.34) and reduced large LDL (r = 0.34), an overall increase in the number of LDL particles (r = −0.44), and a decrease in HDL size (r = 0.41) as a result of depletion of large HDL particles (r = 0.38) and a modest increase in small HDL (r = −0.21; all P < 0.01). These correlations were also evident when only normoglycemic individuals were included in the analyses (i.e., IS + IR but no diabetes), and persisted in multiple regression analyses adjusting for age, BMI, sex, and race.” [27]

*of note: “When compared with IS [insulin sensitive], the IR [insulin resistant] and diabetes subgroups exhibited a two- to threefold increase in large VLDL particle concentrations (no change in medium or small VLDL), which produced an increase in serum triglycerides; a decrease in LDL size as a result of an increase in small and a reduction in large LDL subclasses, plus an increase in overall LDL particle concentration, which together led to no difference (IS versus IR) or a minimal difference (IS versus diabetes) in LDL cholesterol” as well as “these insulin resistance-induced changes in the NMR lipoprotein subclass profile predictably increase risk of cardiovascular disease but were not fully apparent in the conventional lipid panel.”

YUNOLDL

The focus on LDL-cholesterol and Total cholesterol is nothing new. In speaking with doctors TheFatNurse has encountered, medical as well as PA & NP schools are lagging a bit behind when it comes to more current lipoprotein research. And while targeting LDL-Cholesterol remains the “gold standard.” The associations between LDL-cholesterol and heart disease aren’t as strong as you might think. In this study of 231,986 hospitalizations from 541 hospitals of CAD hospitalizations from 2000 to 2006 with documented lipid levels in the first 24 hours of admission, [28] they found

“mean lipid levels were LDL 104.9 +/- 39.8, HDL 39.7 +/- 13.2, and triglyceride 161 +/- 128 mg/dL.”

In otherwords, the average person admitted actually had Near optimal/above optimal LDL-cholesterol! However, you’ll notice that the average HDL was below target

And what about Triglycerides? You’ll see that they were elevated:

Triglycerides on average were borderline high in this group (although the standard deviation was pretty wide). So while LDL-Cholesterol, “the primary target of therapy,” was pretty good, perhaps just as much emphasis should be placed on HDL cholesterol and Triglycerides or even the evaluations of other lipid parameters such as the Non-HDL cholesterol and TG/HDL ratio we discussed earlier.

That’s not to say LDL-Cholesterol is worthless, it can have good predictive value for those who are concordant. Versus those who are discordant. TheFatNurse talks about this briefly and why it’s important in this other comic from TheFatNurse’s comic series. Here’s a little snippet on why discordance is not good:

ConDis

What is LDL-P? These are the actual number of LDL lipoproteins themselves! Apo-B measurements are also a way to get LDL-P numbers and the Non-HDL marker we discussed earlier can act as a surrogate for Apo-B and LDL-P (although Non-HDL is not as accurate). When we get a regular lipid panel, we are only looking at the cholesterol in the lipoproteins and not the lipoproteins themselves! Here are some pictures to illustrate. For example, say your doctor informs you that you have 16 oz of Cholesterol as you can see below:

Screen Shot 2013-03-01 at 12.35.28 AM

16 Oz of Thai Ice Tea *Ahem* TheFatNurse means 16 oz of cholesterol

In order to get that 16 oz measurement, the lab needed to break apart the lipoproteins that were carrying the cholesterol in the first place. Usually the amount of cholesterol can correlate with the number of lipoproteins…but not always. For example, was this 16 oz of cholesterol carried in lipoproteins the size of shot glasses?

Screen Shot 2013-03-01 at 12.36.20 AM

The 16 oz of cholesterol spread over six smaller shot glasses *Ahem* Lipoproteins

Or was it carried in the form of rock glasses?

Screen Shot 2013-03-01 at 12.36.49 AM

The same 16 oz of cholesterol carried in larger Rock *Ahem* I mean larger lipoproteins

As you can see it’s impossible to really know the characteristics of the lipoproteins based off just the cholesterol itself! In the first example, the 16 oz of cholesterol was carried in 6 small shot glasses/lipoproteins. In the second example, the 16 oz of cholesterol was carried in 2 larger rock glasses/lipoproteins. The first example is more atherogenic while the second one is less. You can see two different characteristics emerge at this point: size and number. Whether it’s the size or the total number of lipoproteins that is more atherogenic is hotly debated, but either characteristic is a much better predictor of risk than just looking at just the cholesterol itself. In many people LDL-cholesterol correlates (what is known as concordance) well with the number of LDL particles but not always. When LDL-cholesterol doesn’t correlate well, it’s said to be discordant.

Some support for looking at other markers besides LDL-cholesterol due to discordance can be found below:

“For individuals with discordant LDL-C and LDL-P levels, the LDL-attributable atherosclerotic risk is better indicated by LDL-P.” [29]

“…significant discordance between LDL and non-HDL cholesterol levels in diabetes patients with high triglycerides or the MS. This might explain patients’ high residual CV risk despite having achieved their desirable LDL cholesterol levels.” [30]

“Discordance analysis demonstrates that apoB is a more accurate marker of cardiovascular risk than non-HDL-C.” [31]

“Four-hundred twenty-eight (18%) of children were in the LDL-P < LDL-C subgroup and 375 (16%) in the LDL-P > LDL-C subgroup. Those with LDL-P > LDL-C had significantly greater body mass index, waist circumference, homeostatic model of insulin resistance, triglycerides, systolic and diastolic blood pressure… a discordant atherogenic phenotype of LDL-P > LDL-C, common in obesity, is often missed when only LDL-C is considered” [32]

“Many patients with type 2 diabetes mellitus (T2DM) have relatively normal levels of low-density lipoprotein (LDL) cholesterol yet have increased risk for cardiovascular events…despite attainment of LDL cholesterol <50 mg/dl or non-HDL cholesterol <80 mg/dl, patients with diabetes exhibited significant variation in LDL particle levels, with most having LDL particle concentrations >500 nmol/L, suggesting the persistence of potential residual coronary heart disease risk.” [33]

“Both men and women with increasing levels of apoB and non-HDL-c were more obese, had higher blood pressure and fasting glucose levels, and a more atherogenic lipid profile…Less clear differences in CV risk profile and subclinical atherosclerosis parameters were observed when participants were stratified by LDL-c level. Furthermore, apoB but not LDL-c detected prevalent CVD, and non-HDL-c only detected prevalent CVD in men…Our data support the use of first apoB and secondly non-HDL-c above LDL-c for identifying individuals from the general population with a compromised CV phenotype.” [34]

“A recent large meta-analysis with >60,000 patients in statin trials found that when LDL-C was low (LDL-C <100 mg/dl), but non–HDL-C was elevated (non–HDL-C >130 mg/dl) there was an increase in cardiovascular events compared with those with both elevated LDL-C and non–HDL-C…Although both lipid profiles represent a patient at high residual risk for a major adverse cardiac event, the patient with the low LDL-C (<100 mg/dl), but with a discordantly high non–HDL-C (>130 mg/dl), is the type of patient who may slip through the cracks because the at-goal LDL-C may mislead the clinician into believing the patient is adequately treated…Should non–HDL-C replace LDL-C as the main target of therapy? The advantages appear clear: non–HDL-C is a better risk predictor, can be performed in a nonfasting state, and does not incur any additional costs to the healthcare system.” [35]

Perhaps highlighting the imporatnace of the awareness of these other lipid markers: 44% of clinical providers could not calculate Non-HDL when given a standard lipid panel and there was confusion amongst not just primary care providers, but cardiologists as well. [36]

“…non-HDL-C appears to be an indirect way of estimating apoB. We argue that we should integrate the information from non-HDL-C and apoB for better risk assessment and a better target of therapy” [37]

“This meta-analysis is based on all the published epidemiological studies that contained estimates of the relative risks of non-HDL-C and apoB of fatal or nonfatal ischemic cardiovascular events. Twelve independent reports, including 233 455 subjects and 22 950 events, were analyzed…Whether analyzed individually or in head-to-head comparisons, apoB was the most potent marker of cardiovascular risk (RRR, 1.43; 95% CI, 1.35 to 1.51), LDL-C was the least (RRR, 1.25; 95% CI, 1.18 to 1.33), and non-HDL-C was intermediate (RRR, 1.34; 95% CI, 1.24 to 1.44)…We calculated the number of clinical events prevented by a high-risk treatment regimen of all those >70th percentile of the US adult population using each of the 3 markers. Over a 10-year period, a non-HDL-C strategy would prevent 300 000 more events than an LDL-C strategy, whereas an apoB strategy would prevent 500 000 more events than a non-HDL-C strategy.” [38]

In most studies, both apo B and LDL-P were comparable in association with clinical outcomes. The biomarkers were nearly equivalent in their ability to assess risk for CVD and both have consistently been shown to be stronger risk factors than LDL-C. We support the adoption of apo B and/or LDL-P as indicators of atherogenic particle numbers into CVD risk screening and treatment guidelines. [39]

III. Going Over Dietary Cholesterol and Fat

For individuals who are not at LDL cholesterol goal, the instructor recommended that cholesterol should be limited to <200 mg/day and total saturated fat reduced to less than 7% of daily caloric intake. However,despite the instructor’s recommendations, there has been some debate on whether the guidelines on dietary cholesterol are that effective or even necessary.

“The European countries, Australia, Canada, New Zealand, Korea and India among others do not have an upper limit for cholesterol intake in their dietary guidelines. Further, existing epidemiological data have clearly demonstrated that dietary cholesterol is not correlated with increased risk for CHD. Although numerous clinical studies have shown that dietary cholesterol challenges may increase plasma LDL cholesterol in certain individuals, who are more sensitive to dietary cholesterol (about one-quarter of the population), HDL cholesterol also rises resulting in the maintenance of the LDL/HDL cholesterol ratio, a key marker of CHD risk.” [40]

Sincerely, Sugar

Sincerely, Sugar

Physiologically, as we mentioned earlier, most of the cholesterol we absorb is biliary in origin rather than dietary. Therefore, would decreasing cholesterol consumption down to <200 mg/day even have a meaningful impact? The focus on dietary cholesterol can also take attention away from dietary plant sterols (phytosterols). The difference between these plant sterols and cholesterol (sterols from animals) is that plant sterol absorption is minimized compared to cholesterol:

“Dietary cholesterol comes exclusively from animal sources, thus it is naturally present in our diet and tissues. It is an important component of cell membranes and a precursor of bile acids, steroid hormones and vitamin D. Contrary to phytosterols (originated from plants), cholesterol is synthesised in the human body in order to maintain a stable pool when dietary intake is low…conversely, phytosterols are poorly absorbed and, indeed, rapidly excreted. Dietary cholesterol content does not significantly influence plasma cholesterol values, which are regulated by different genetic and nutritional factors that influence cholesterol absorption or synthesis. Some subjects are hyper- absorbers and others are hyper-responders, which implies new therapeutic issues. Epidemiological data do not support a link between dietary cholesterol and CVD.” [41]

Without going into too much detail (save that  for a future post), people who are hyperabsorbers may end up absorbing phytosterols into the plasma where some evidence is showing that they can be atherogenic if not more so than cholesterols in the artery wall. After all, there is a disease called phytosterolemia (also known as sitosterolemia) [42] that causes individuals to die at an early age from heart disease due to elevated absortion of these phytosterols. Remember, atherosclerosis occurs when a sterol is deposited into the arteries to elicit an inflammatory response; this can be a cholesterol or a phytosterol. Most people don’t have to worry about this tho and this point on phytosterols was only mentioned to show that there are other sterols out there than just cholesterol which can impact atherosclerosis. As expected, there was no mention of hyper absorbers in the class which is fair since this is newer emerging data.

And what about the saturated fat limitation? TheFatNurse has beat to death the notion that dietary saturated fat (and total fat) is responsible for coronary heart disease, but here’s a couple of meta analyses that you can look over yourself:

“Meta-Analysis of Cohort Studies of Total Fat and CHD…Intake of total fat was not significantly associated with CHD mortality…Intake of total fat was also unrelated to CHD events”

“Meta-Analysis of Cohort Studies of SFA and CHD…Intake of SFA was not significantly associated with CHD mortality…Similarly SFA intake was not significantly associated CHD events…no significant association with CHD death.”

“Randomized Controlled Trials of Dietary Fat and CHD…Meta-Analysis of Randomized Controlled Trials of Fat-Modified Diets and CHD…the low-fat diets did not affect CHD events”

“The available evidence from cohort and randomised controlled trials is unsatisfactory and unreliable to make judgement about and substantiate the effects of dietary fat on risk of CHD.” [43]

“…there is no significant evidence for concluding that dietary saturated fat is associated with an increased risk of CHD or CVD.””More data…needed to elucidate whether CVD risks are likely to be influenced by the specific nutrients used to replace saturated fat.” [44]

“Compared with participants on low-fat diets, persons on low-carbohydrate diets experienced a slightly but statistically significantly lower reduction in total cholesterol (2.7 mg/dL; 95% confidence interval: 0.8, 4.6), and low density lipoprotein cholesterol (3.7 mg/dL; 95% confidence interval: 1.0, 6.4), but a greater increase in high density lipoprotein cholesterol (3.3 mg/dL; 95% confidence interval: 1.9, 4.7) and a greater decrease in triglycerides (-14.0 mg/dL; 95% confidence interval: -19.4, -8.7).” [45]

“No clear effects of dietary fat changes on total mortality or cardiovascular mortality “”There are no clear health benefits of replacing saturated fats with starchy foods (reducing the total amount of fat we eat).” [46] *

There are other interesting individual studies challenging the notion of saturated fat and heart disease, but instead of continuing the onslaught of posting studies, it may be more interesting to go over the mechanisms of dietary fat. After all, it seems like it would be common sense that ingestion of saturated fats would lead to more fats in the blood stream right? However, this does not happen and.its more likely one would find increased levels of lipids, in particular, triglycerides in your blood stream with the consumption of carbohydrate. You can see in one of the meta-analysis above from Hu et al 2012 that low carb diets often yielded less total cholesterol, less LDL-cholesterol, more HDL-cholesterol and less triglycerides. How can this be?

The best way to view this is to break apart from the conventional “a calorie is a calorie.” While a calorie is a calorie is true by its definition to raise the temperature of 1 gram of water through 1 °C, this view often leads to people not realizing that calories from different sources have different effects hormonally and on the body’s regulatory system. Carbohydrates, for example, stimulate insulin secretion and effects the availability of energy sources such as free fatty acids.

IV. Going Over Metabolism of Fat in The Body

While the metabolic processes of dietary fat can be complex, the basic concepts can be broken down into a few key ideas. The main idea, as mentioned before, is to stop viewing, “a calorie is a calorie.” A calorie from fat, protein or carbohydrate can exert different hormonal and therefore regulatory effects on the body independent of its energy content.

For example, keeping calories the same but switching the amount of fat and carbohydrate changes the regulatory oxidative pathways of muscles in as few as three days, “isoenergetic high-fat/low-carbohydrate diet (HF/LCD) for 3 days with muscle biopsies before and after intervention. Oligonucleotide microarrays revealed a total of 369 genes of 18 861 genes on the arrays were differentially regulated in response to diet…” [47]

An even simpler example of this process is how dietary carbohydrates lead to a rise in insulin. Unfortunately, most of the focus on insulin is in its ability to bring blood sugar down in the body. This shouldn’t be surprising since regulation of blood sugar is such a huge treatment plan of healthcare today.

When the regulatory process of insulin and blood sugar is disrupted, say for example in the development of T2 Diabetics, issues such as hyperglycemia (high blood sugar) can occur which can eventually lead to insulin resistance and the development of the metabolic syndrome which is increased triglycerides, decreased HDL, elevated blood pressure, increased abdominal girth and impaired fasting blood sugar. How can it be that carbohydrates have the potential to impact all these 5 factors? Since this post is about lipids, we’ll limit the discussion to mostly increased triglycerides, low HDL and impaired fasting glucose (which indirectly impacts lipids and lipoproteins) for now and explore the other two elements in a latter post.

The body has an innate ability to convert excess glucose into triglycerides.  Indeed, there is a protein in the liver appropriately named carbohydrate response element binding protein (ChREBP) that stimulates lipogenesis in the liver in response to carbohydrate. [48]

When dietary carbohydrates are decreased, lipid metabolism in the body changes and fat oxidation (also known as beta oxidation which specifically refers to the breakdown of triglycerides into free fatty acids for energy) occurs irrespective of the amount of calories (such as fasting) one ingests. “Changes in plasma glucose, free fatty acids, ketone bodies, insulin, and epinephrine concentrations during fasting were the same in both the control and lipid studies…These results demonstrate that restriction of dietary carbohydrate, not the general absence of energy intake itself, is responsible for initiating the metabolic response to short-term fasting.” [49]

Not only is lipid oxidation increased, but expression of lipogenesis pathways are decreased when carbohydrates are decreased and fat increased in animal models (Although this supports the point TheFatNurse is trying to make, please remember that animal model can sometimes have limitations in applicability to humans). “Microarray analysis of liver showed a unique pattern of gene expression in KD [ketogenic diets which are high fat low carb], with increased expression of genes in fatty acid oxidation pathways and reduction in lipid synthesis pathways…these data indicate that KD induces a unique metabolic state congruous with weight loss.” [50]

Since carbohydrates (especially in the form of sugar) can have an effect on blood sugar, one of the recommended advice that we’re given is to exercise more. Indeed, one of the ways exercise helps to bring down blood sugar is the generation of what are called GLUT-4 receptors in the muscles and fat tissue of the body which allow glucose transport and therefore reducing some of the blood sugar levels in the body.

However, the consumption of carbohydrates can lead to these GLUT-4 receptors disappearing faster when compared to a consumption of lower carbohydrate after exercise. “…increases in GLUT4 mRNA and protein reversed completely within 42 h after exercise in rats fed a high-carbohydrate diet. In contrast, the increases in GLUT4 protein, insulin-stimulated glucose transport, and increased capacity for glycogen supercompensation persisted unchanged for 66 h in rats fed a carbohydrate-free diet…These findings provide evidence that prevention of glycogen supercompensation after exercise results in persistence of exercise-induced increases in GLUT4 protein and enhanced capacity for glycogen supercompensation.” [51]

So far we’ve set the stage that increased carbs can increase the blood glucose, increase insulin and therefore increase lipogenesis which increases Triglycerides. Increased triglycerides, as you know, is one of the factors of metabolic syndrome. By contrast, decreasing carbohydrate can have the opposite beneficial effect of lowering Triglyerides. How does it do this?

Again, the increase of circulating triglycerides is not from increasing consumption of fat. It’s when individuals become insulin-resistant, from the increasing consumption of excessive carbohydrates or sugar which impaires glucose to be taken up in the cells which makes the liver convert the glucose to triglycerides. This occurs irrespective of differences in obesity in an individual. What is commonly taught is that obesity leads to insulin resistance, but individuals can be insulin resistant and lean as well as shown here:

“Following ingestion of two high carbohydrate mixed meals, net muscle glycogen synthesis was reduced by ≈60% in young, lean, insulin-resistant subjects compared with a similar cohort of age–weight–body mass index–activity-matched, insulin-sensitive, control subjects. In contrast, hepatic de novo lipogenesis and hepatic triglyceride synthesis were both increased by >2-fold in the insulin-resistant subjects. These changes were associated with a 60% increase in plasma triglyceride concentrations and an ≈20% reduction in plasma high-density lipoprotein concentrations but no differences in…intraabdominal fat volume.”

“These data demonstrate that insulin resistance in skeletal muscle, due to decreased muscle glycogen synthesis, can promote atherogenic dyslipidemia by changing the pattern of ingested carbohydrate away from skeletal muscle glycogen synthesis into hepatic de novo lipogenesis, resulting in an increase in plasma triglyceride concentrations and a reduction in plasma high-density lipoprotein concentrations.” [52]

As far as how the liver actually convert glucose to triglycerides and how triglyceride production is decreased in the liver…there are several pathways by which this occurs but the main idea is the lowered inputs of Plasma Fructose, Plasma Glucose and Insulin by the consumption of dietary fat (even saturated fat) leads to decreased TGs. If you want more details on the biochemistry of carbohydrate and lipogenesis you can read more about it here: [53]

So what about HDL-cholesterol? Why is HDL-cholesterol decreased in Metabolic syndrome? As shown in the previous study, HDL-cholesterol tends to go down when Triglycerides go up. This shouldn’t be surprising since they are both measurements of metabolic syndrome. This is also why the TG/HDL ratio mentioned earlier is also a predictor of insulin resistance.

Along with decreasing Triglycerides, decreasing the amount of carbohydrates also raises the HDL cholesterol. This is important to note since policy recommends daily intakes of 30% total fat or less (with less than 10% of the saturated) and 60% carbohydrates. Studies showing the benefits of increased fat consumption and decreased carbohydrate consumption have vastly different ratios than the ones shown here obviously.

The benefits of reducing carbohydrate and increasing fat consumption are often ignored and suggestions to raise HDL are usually conventional advice like exercising more, glass of wine and losing weight. However, this increase in HDL tends to occur more to those who had elevated HDLs to begin with and not as pronounced with those who have low HDL levels to start with. This suggest that conventional wisdom may not be effective for those who already have metabolic syndrome:

“…the effects of physical activity, alcohol, and weight reduction on HDL-C levels may be, to a large extent, dependent on the initial level with the greatest improvement achieved in subjects with high HDL and the least improvement in those having low HDL-C levels.” [54]

But why exactly does HDL cholesterol tend to decrease? The answer may lie in the elevated triglycerides. One of the problems about teaching these lipid markers is that they are often portrayed as static entities rather than dynamic entities that interact with one another. In this case, elevated triglycerides can lead to decreased HDL cholesterol through catabolism in the megalin/cubillin processes in the kidney.

“…intravascular modeling of HDL bylipases and lipid transfer factors….determinant of the rate of HDL clearance from the circulation. CETP-mediated heteroechange of HDL cholesteryl ester (CE) with chylomicron and VLDL (TG-rich lipoproteins, TRL) triglycerides results in CE depletion and TG enrichment of HFL. TG-rich HDL releases lipid poor apoA-1 and HDL remnant particles. Lipid-poor apoA-1 is filtered by the renal glomerulus and then degraded by proximal tubular cell receptor such as cubili/megalin system.” [55]

There’s a lot of greater details in that quote I extracted from the study but if you’re interested in learning these details TheFatNurse’s HDL/Triglyceride comic covers most of the details in easy picture analogic fashion.

Anyways this post is starting to deviate a bit from it’s original purpose of critiquing the lipid lecture. However, the little side adventure of exploring TGs, HDLs and insulin resistance in more depth was to show that LDL cholesterol is not the only nor always the best indicator for heart disease of which insulin resistance is highly associated with. Unfortunately the class was taught to use LDL-cholesterol as a target goal which means intervention methods focused primarily on lowering LDL-cholesterol (and not necessarily the other markers as much although the instructor did mention targeting HDL and TGs but only briefly compared to LDL cholesterol).

V. An Unexpected Twist

However…things then took an unexpected turn! For example, the next slide was titled, “Lack of Evidence for LDL Goal.” Surprisingly, the instuctor pointed out that aiming for LDL cholesterol targets did not always yield reductions in events or mortality. One slide even said that trials which lowered cholesterol did not always improve outcomes! This is not surprising as we have covered, but it is surprising that it is being presented  in a formal setting.

The instructor then informed the class of additional studies that showed pharmaceutical treatment was beneficial despite the controversies on LDL cholesterol as a target goal. One of which was the HPS study which showed you can reduce all cause total mortality in 1 out of every 57 patients with simvastatin if given for at least 5 years. [56]

However, TheFatNurse had some criticism for the way the instructor presented these trials. Specifically, the instructor didn’t make it clear whether the studies were for primary or secondary prevention groups. There are benefits for pharmaceutical interventions, such as statins, for secondary prevention (in people with known CHD disease or its equivalent risk) although the benefits are not always as dramatic as their commercials may indicate. For primary groups (people without any CHD) the benefits are unclear if any at all. More on this in a bit…

If you want to look up the population being studied, you’ll have to find the paper and hope the patient population is described. But a good way to save time is to actually go to: http://www.trialresultscenter.org which describes the patient population along with any inclusions and exclusions for the methodology. They also list the end point goals of each trial. While the instructor did mention some populations, after diving in more details TheFatNurse learned other information about the populations being studied.

One had patients with end-stage renal disease on hemodialysis, another had adults (aged 40-80 years) with coronary disease, other occlusive arterial disease, or diabetes, one trial only used MI survivors, and  another had patients with a history of cardiovascular disease, high triglycerides, and low levels of HDL cholesterol. If TheFatNurse didn’t look up any of this information, none of this demographic information would have been known! This is important because we need to ask ourselves if the results from these high-risk populations are appropriate to extract for a general primary population.

Back to the primary and secondary issue, one meta analysis found, “This literature-based meta-analysis did not find evidence for the benefit of statin therapy on all-cause mortality in a high-risk primary prevention set-up” [57] while the Cochrane Review found some minor benefits in primary populations but point out there are “shortcomings in the published trials and we recommend that caution should be taken in prescribing statins for primary prevention among people at low cardiovascular risk.” [58] This is still a hotly debated subject to this day and you can read an interesting debate/exchange between Dr. Rita Redberg from UCSF vs Dr. Roger Blumenthal of John Hopkins on the issue of statin use in primary populations. [59]

Even after showing that LDL cholesterol is not a good target the instructor ended by recommending we still continue to target LDL-cholesterol since it’s still in the guidelines. This rationale was disappointing, as mentioned earlier, since Non-HDL is also a target in the guidelines…yet it was never mentioned by the instructor. Additionally, TheFatNurse was also a little disheartened with the lack of discussion on carbohydrate control on the lipid profile. While the instructor had recommended the reduction of saturated fat and dietary cholesterol in class, TheFatNurse had a private conversation with the instructor between lectures and guess what? The instructor actually knew all about dietary carbohydrate and it’s effect on triglycerides and HDL-cholesterol. How come he didn’t mention carbohydrate reduction and make a case for eating fat then? In either case, I will give him credit for at least introducing doubt about LDL-cholesterol as the end all be all risk marker.

Summary: TheFatNurse finally had the lipid intervention lecture in school. As expected, it focused mainly on targeting LDL cholesterol. Advance lipid testing/targets were not mentioned which is to be expected as well…but the instructor didn’t even mention anything about Non-HDL cholesterol! This was rather disturbing since there was such an emphasis on LDL-cholesterol due to the ATP 3 guidelines…but even ATP 3, for all it’s flaws, mentions using Non-HDL cholesterol! The instructor also mentioned avoiding dietary saturated fat and cholesterol, which was expected and the potential benefits of carbohydrate reduction was not mentioned at all. However, the class then took a 180 with the instructor showing some studies that targeting LDL-cholesterol may not always yield the outcomes we want! TheFatNurse has to give props to the instructor for that…but then another 180 happened with the instructor saying we should still focus on reducing LDL cholesterol since it’s in the guidelines.

Some studies were then shown to the class on the support of pharamaceutical intervention. However, the instructor didn’t make it clear what the study populations were for some of the trials. This could lead to confusion in not knowing whether the results of trials were applicable to primary or secondary prevention groups. In the end, TheFatNurse was happy to at least see, even if brief, LDL-cholesterol being doubted formally in a classroom setting.

* The Cochrane group does recommend the replacement of saturated fat for unsaturated fat due to a reduction of 14% in cardiovascular events with the replacement of saturated fats with unsaturated fats, but this effect was only seen in studies of men (not those of women) lasting longer than two years and with populations that had cardiovascular risk to begin with and not the general population. They point out the effect on heart attacks and strokes individually were not clear.

Is The Paradigm Shift Starting? Media Updates and Carpal Tunnel

TheFatNurse is Alive and Well despite the lack of updates. Had to take on finals and TheFatNurse is happy to report they never stood a chance! In the meantime, lots of changes occurred since the last update in regards to the media and some new things TheFatNurse learned on carpal tunnel and diabetics.

Doctor Oz…leading the way!? If you’ve followed this blog then you’ll know TheFatNurse is no fan of Dr. Oz who often regurgitates the existing paradigm and has condemned fat as a evil. So you can imagine TheFatNurse’s surprise when Dr. Oz had not ONE but TWO shows that challenged the existing paradigm on diet! Last week Dr. Oz had Dr. Stephen Sinatra & Dr. Jonny Bowden talking about how the current view on cholesterol is all wrong, that there is nothing generally wrong with eating saturated fat, and that cholesterol in general is good for us.

WHOOOA

TheFatNurse’s reaction to this Episode

None of this is new to TheFatNurse…but seeing it on the Dr. Oz show, a huge influential media source, was too surreal! Many days and nights TheFatNurse was laughed at for questioning the existing paradigm…well perhaps no more! The show was progressing nicely until Doctor Oz attempted to use an illustration on how LDL and HDL works…something about a suitcase? Simply put, this best explains how TheFatNurse felt about it:

Let your Guests Explain How it Works!

Kudos to Dr. Oz for bringing up the subject matter, but if you’re interested in how LDL and HDL relate to heart disease check out the For All Ages FatNurse comics on Cholesterol in General and HDL/Triglycerides. However, despite the kudos, TheFatNurse was deeply disturbed by one of Dr. Oz’s comments:

I’m blown away by these side effects you’re reporting. You’re saying there’s data that statin drugs cause diabetes…

For reals? This was big news earlier in the year (February 2012) when the FDA announced they were adding warnings to statins for this very thing. It’s right here on the FDA website if you’re curious. TheFatNurse is just a little shocked Dr. Oz didn’t know that.

People being treated with statins may have an increased risk of raised blood sugar levels and the development of Type 2 diabetes.

However, TheFatNurse was happy to hear Dr. Oz ending the online segment by informing people that sugar is a bigger problem than fats in the diet. What is a bit peculiar is how the online episodes cutoff 1/4 of the show about cholesterol. The part they cutoff is the segment exonerating dietary fats and dietary cholesterol. TheFatNurse was fortunate enough to come across the missing segment tho:

The second Oz show that got TheFatNurse all excited occurred two weeks ago and challenged the paradigm of healthy whole wheat grain. This episode featured Dr. William Davis, a cardiologist, and the author behind Wheat Belly. Again, nothing new if you’ve been following this blog but to see the idea that “healthy whole grain wheat” as unhealthy being discussed so openly on Dr. Oz is just amazing.

Another media boost challenging the dominant paradigm on fat came from CBN news which did a segment on how a ketogenic diet (super low carb & high fat) could help with cancer by “starving” the center cells of glucose.

Although it wasn’t easy, Hatfield stopped eating carbohydrates, which turn into glucose inside your body. Cancer cells love glucose and need it so badly, that if you stop giving it to them, they die.

TheFatNurse hasn’t looked into the medical literature on the subject for clinical trials and what not but this is certainly something worth following up on in the future.

Speaking of blood glucose, TheFatNurse never knew how much more at risk people with impaired blood glucose such as diabetics or people with metabolic syndrome were at developing carpal tunnel syndrome. In this study,

metabolic syndrome was found to be three times more common in patients with CTS and CTS was more severe in patients with metabolic syndrome when compared with those without metabolic syndrome.

To keep it short, what happens is when glucose is elevated and around proteins such as collagen, elastin and fascia in tendons, it goes through something called glycosylation. This basically means that the glucose and proteins combine together. This impairs the function of things such as collagen, elastin and fascia. In nerves, glucose is converted to sorbitol which attracts water. Nerves also have collagen and elastin components. So as you can see in the picture below, when you have all this glycosylation occurring on the median nerve and the surrounding tendons in an enclosed space like the carpal tunnel it’s bad news.

Picture by Wilfredor

TL;DR: Looks like the media may be more friendly and picking up on information that goes against the traditional paradigm than before. Who knows what direction their influence is going to direct things in the future? Also carpal tunnel and hyperglycemia may be closely related.

Low Carb Better Than Low Fat at Reducing CVD Risk?

Check out this new article from professional.diabetes.org with Dr. Krauss! Being one of the more influential researchers in the field, it’s a big influence when he makes statements like the ones featured in the article. Statements such as:

“It is certainly advisable for overweight individuals to lose weight, but for people who cannot achieve a sufficient weight loss, just reducing carbohydrate intake appeared to be quite effective in improving atherogenic dyslipidemia.”

“…you can go high on fats and if you go low on carbs, especially sugars and white starch, and limit red meats, you don’t have to worry too much about saturated fat…”

Be sure to check it out!

What if TheFatNurse Was Secretly a Double Agent?

Sometimes the news of saturated fats not being so unhealthy can come as a shock and met with huge denial. Every now and then TheFatNurse is met with these critiques…the response? Well actually TheFatNurse didn’t do everything in this comic but definitely thought through the events!

 

Fat Research During the MadMen Era

My friends keep obsessing over the new season of MadMen, so lets take a look at some of the landmarks of obesity related topics in this era. This era is well known for establishing Ancel Key’s Lipid hypothesis which states saturated fat increases cholesterol and increased cholesterol is a risk for heart disease therefore reduction of cholesterol and saturated fat reduced heart disease. This hypothesis is still widely accepted today. However, contradictory evidence was emerging around the same time. Two notable scientists providing an alternate hypothesis to heart disease at this time were Peter Ahrens and John Gofman.

John Gofman is famous for pioneering cholesterol research. While everyone was focusing on cholesterol as the circulating fat during the 50s, Gofman pointed out that the body circulated more lipid like substances than just cholesterol such as triglycerides. Additionally, there was also the lipoproteins that were involved in these lipids. This discovery naturally lead to the question: is there more to this story than just cholesterol? However, due to the technology at the time, it was only feasible to measure cholesterol (total).

With time, scientists eventually discovered three important Lipoproteins involved with cholesterol: HDL (the so called good one), LDL (what we commonly think of as the bad one) and VLDL (which carries most of the triglycerides). While everyone else was concerned about total cholesterol, Gofman realized that LDL seemed to be in larger amounts in patients with atherosclerosis independent of their total cholesterol. Therefore, Gofman pointed out that measuring total cholesterol was useless. However, even more compelling, was Gofman’s research on VLDL.

Gofman discovered that eating saturated fats could raise LDL which would fall in line with our current way of thinking. However, he also discovered that eating more carbohydrates would raise VLDL levels! The implications of this finding showed the potential dangers of using a low fat – high carbohydrate diet. For example, Gofman pointed out that the substitution of saturated fats for carbohydrates (the “carbohydrate factor” as he put it) could potentially cause more harm for individuals if it elevated their VLDL levels too high. This was of particular concern since cholesterol levels during this era was measured as total cholesterol and not into more specific subsets.

John W. Gofman

“If LDL was abnormally elevated, then this low-fat diet might help, but what Gofman called the ‘carbohydrate factor’ in these low-fat diets might raise VLDL so much that the diet would do more harm than good.”

– Gary Taubes, Good Calories Bad Calories

Another prominent scientist at this time was Peter Ahrens who is associated with terming the phenomenon of carbohydrate-induced lipemia. Simply put, this is circulation of fatty triglycerides in the blood (carried by VLDLs as shown from Gofman’s research) which is a risk for heart disease. The question is: was a person more likely to have this circulating systemically on a high carb or a high fat diet?

Since VLDLs were more likely to increase under carbohydrates consumption, you would be right if you said a diet focused more on carbohydrates. Ahrens demonstrated this by showing blood serum from the same patient following a high fat or high carbohydrate meal. The test tube was cloudy with triglycerides if they had eaten the carbohydrate diet but clear if they had eaten the high fat diet. However, during this period, having a high triglyceride level was still being questioned whether or not to play a role in heart disease. Ahrens warned the lipid hypothesis needed more questioning before low-fat diets (which would mean an increase of calories from carbohydrates) should be recommended since they did not know whether carbohydrates, fats or some other factor played a role in heart disease.
***Of note, Ahrens showed that a high carbohydrate diet would have less triglyceride levels if the total caloric intake was very low. A point he used to argue certain Asian countries having lower heart disease despite having a high carbohydrate diet at the time.

Margaret Albrink, at the metabolic division of Yale Medical School would provide some observations on the importance of triglycerides. Her findings showed high triglycerides were more common than elevation of cholesterol in patients with cerebral, coronary and aortic atherosclerosis. And that potential accumulation of triglycerides may be the most common lipid derangement in coronary artery disease.

Albrink presented her results to the association of the American Physicians but was met with anger and disbelief. This occurred only recently after the American Heart Association decided to accept and endorse Ancel Key’s idea of saturated fat and cholesterol (Lipid hypothesis) being the culprit. Albrink would continually be attacked by proponent’s of the lipid hypothesis. However, she would receive more support from other scientists later such as Nobel laureate Joseph Goldstein who found elevated triglyerides just as common if not more so than cholesterol in over 500 patients with heart disease. Even more interesting was a study done by Peter Kuo which showed:

More than 90% of the 286 patients were found to have hyperglyceridemia derived from increased endogenous lipogenesis from carbohydrate. This abnormal carbohydrate sensitivity was revealed with an ad libitum carbohydrate (35% to 40%) diet. Since lipoproteins synthesized from carbohydrates were shown to be rich in both triglyceride and cholesterol, carbohydrate-sensitive hyperglyceridemia was frequently found in association with hypercholesteremia. The abnormal metabolism was controlled by a sugar-free diet, with a carbohydrate allowance of 125 to 150 gm supplied as starches.

So 90% of the subjects had elevated triglycerides related to carbohydrate consumption. Additionally, since VLDLs carry triglycerides and cholesterol (majority triglycerides), that could potentially mean increases in cholesterol levels could be related to carbohydrate consumption as well. Interestingly enough, the elevated triglycerides and cholesterol were controlled when patients were put on limited carbohydrates…

Even more interesting was an editorial put out by the Journal of the American Medical Association about these new discoveries:

“Research,like therapeutics, experiences cyclic fads. These are characterized by a rush of investigators towards an avenue of research initiated by publication of a few promising studies. For nearly fifteen years, an almost embarrassingly high number of researchers boarded the “cholesterol bandwagon” in pursuit of understanding of atherosclerosis. This fervent embrace of cholesterol to the exclusion of other biochemical alterations resulted in a narrow scope of study of a disease which is probably multifaceted in causation. Fortunately, other fruitful approaches have been made possible in the past few years by identification of the fundamental role of such factors as triglycerides and carbohydrate metabolism in atherogenesis.”

Somehow tho, saturated fats and cholesterol being the culprit behind heart disease has still become unquestionable medical facts to many practitioners and thus society. Just how sure are we of this?

Peter Ahrens

“Some thought him to be obtuse or stubborn, as he refused to endorse claims that changing our diets by lowering cholesterol intake would be the sole and most effective weapon to win the battle against heart disease. He was indefatigable in pointing out the necessity of additional clinical research in human subjects to delineate individual differences in response to diet. Unpopular as these views may have been, time has revealed the correctness of his views.
http://www.jlr.org/content/42/6/891.full

Serum Lipids and Cerebral Vascular Disease
ROBERT G. FELDMAN, MD; NEW HAVEN; MARGARET J. ALBRINK, MD
Arch Neurol. 1964;10(1):91-100.

Hyperlipidemia in Coronary Heart Disease I. Lipid levels in 500 survivors of  Myocardial InfarctionJOSEPHL.GOLDSTEIN,WILLIAMR.HAzzmm, HELMUTG.ScinoTT, EDWINL.BIERMAN,andARNoG.MOTULSKYwiththeassistanceof MARYJoLEVINSKIandELLEND.CAMPBELL

Hyperglyceridemia in Coronary Artery Disease and Its Management
Peter T. Kuo, MD JAMA.1967;201(2):87-94. doi: 10.1001/jama.1967.03130020033007

CORONARY HEART DISEASE AND CARBOHYDRATE METABOLISM JAMA.1967;201(13):1040-1041. doi:10.1001/jama.1967.03130130066017CORONARY HEART DISEASE AND CARBOHYDRATE METABOLISM JAMA.1967;201(13):1040-1041. doi:10.1001/jama.1967.03130130066017

Unintended consequences of Medical Dogma

So what do people know about heart disease? Well that is often determined by what their healthcare providers tells them. And what is their healthcare provider likely to tell them? Well, unless they constantly keep up with the latest research, they are likely to tell them the knowledge they were educated with themselves. For myself, I was taught to inform patients that they should eat a low fat (especially of animal fats) and low cholesterol diet (along with low sodium but that’s for another discussion) if they wanted to reduce their incidence of developing heart disease. From my Pathology and Nutrition textbooks:

“A major intervention related to atherosclerosis is encouraging the consumption of a low-fat diet, with those fats being primarily polyunsaturated (from vegetable sources as opposed to animal). Additionally, exercise and weight control are effective in improving lipid profiles. Pharmacologic management of elevated serum lipids is encouraged as a prophylactic intervention”

“Saturated fats are of animal origin. Fats from plant sources usually are unsaturated fats and help reduce health risks (notable exceptions are coconut and palm oil).” 

By now this is common sense right? After all, everybody knows that eating fats is unhealthy and will clog your arteries. But in case you forgot, celebrity doctors like Dr. Oz was on the other day informing viewers that “cutting the fat in half saves a lot of lives.” So how do we know all this? There must be thousands of research studies that show consumption of fat and cholesterol is bad right? Actually…not really.

The connection between heart disease with cholesterol and saturated fat is often taught as eating saturated fat raises cholesterol (LDL) which ends up clogging your arteries. This connection is often cited as if it were unquestionable medical dogma but the evidence of this ever being clear cut is shaky at best. Much has been discussed at length about this by other medical professionals such as the bloggers in my dispatch link. If this is the first time you’ve heard about this, an entertaining documentary about the matter can be found in Fathead by Tom Naughton. For those who want more details, Good Calories, Bad Calories by Gary Taubes provides much more detail about the matter. So instead of going over the subject matter I thought I’d share my thoughts on the unintended consequences of this.

With everybody believing saturated fat and cholesterol are the culprits without solid evidence what has happened?

We now have supermarkets filled with low-fat options that substitute the fat with more carbohydrates when some research is showing carbohydrates as the original culprit.

We’ve developed drugs (Statins) which are now one of the most prescribed medicines that are believed to reduce risks of heart attacks since they lower cholesterol. However, if cholesterol was never a cause for heart disease, then patients have been taking a drug they have never needed while being exposed to adverse risks such as cognitive dysfunction and increased risk of diabetes from these drugs.

We can’t be objective because everything is viewed through this diet-heart hypothesis. A good example of this is the “best diets” list by U.S News which seems to have diets ranked upon how little saturated fat and cholesterol they compose of. It doesn’t bother asking whether the assumption of saturated fat and cholesterol being bad is valid in the first place.

It’s created an obesity stigma where people who can’t lose weight are viewed upon as lazy, incompetent and lack will power. However, if carbohydrates are the original cause, their obesity may have been contributed because they were informed to eat less fat and more carbohydrates!

Defining cholesterol and saturated fats in this manner without reexamining them focuses a lot resources used in research on potentially the wrong cause and treatment.

More importantly, if everything was based on the wrong hypothesis, then the rises in obesity, diabetes, childhood obesity, heart disease, metabolic syndrome, and etc were the cause of unintended consequences!