Last week, during a meeting, Dave brought up the idea for me to go on a formal hunt for any studies that fit the triad outlined in his Low Carb Cholesterol Challenge. I tend to spend a fair bit more time digging through studies than he does, and a fresh set of eyes can help with any task. Plus, by digging through hundreds of papers you never know what you’ll turn up. As a result of this expedition I found some papers that, although not what I was looking for, were certainly fascinating and worth sharing. Although this isn’t all of the papers I came across, it is a list of the most interesting ones, in my eyes. I’ll likely do these roundups occasionally, especially as I come across particularly fun or pertinent studies, so I hope you enjoy.
10. A Look at the Lipid System in Insects
The reason: This study is particularly fascinating for a few different reasons. For one, I had never really consciously thought about insects having a fleshed out lipid system, but also because of the implication of just how old this energy model of the lipid system is. Although, for sure, the insect lipid system is a bit different from ours due to its use of reusable lipid “shuttles” (called lipophorin) and appears to be much less complex than mammalian lipid systems, it does a fantastic job at demonstrating a streamlined version of the energy distribution usage of lipoproteins – just with a bit more exoskeleton involved.
By comparing the mammalian and insect lipoprotein mediated lipid transport systems, we propose the concept that, despite the apparent differences, the two systems are remarkable similar in many aspects of their structure and functioning.
9. Residual Marker Abnormalities In People On Statin Treatment
Cholesterol efflux and metabolic abnormalities associated with low high-density-lipoprotein-cholesterol and high triglycerides in statin-treated coronary men with low-density lipoprotein-cholesterol <70 mg/dl.
The Reason: This study took a look at those on statin therapies, who achieved a target of LDL-C under 70 mg/dL (impressively low, by any standard). They then further separated out the people in the group, only looking at those with low HDL, and high triglycerides, to see what other differences they could see in their markers. Those with low HDL and high triglycerides also had higher insulin levels, poorer cholesterol efflux capacity, and other abnormalities. This highlights that even beyond LDL levels (whatever you think of them) there may be other signs of trouble brewing worth looking out for and addressing.
In conclusion, the decreased cholesterol efflux and metabolic abnormalities found in the dyslipidemia group may contribute to the residual risk observed in the large statin trials and the higher morbidity and mortality in statin-treated coronary patients with low HDL cholesterol even when attaining low-density lipoprotein cholesterol <70 mg/dl.
8. The Predictive Power of LDL Levels in Women
The Reason: Although I’ve come across quite a few of these types of studies by this point, I always find it useful to make a note when I come across another one. This study took a look at lipid markers and their relation to cardiovascular mortality, specifically in women. Similar to the studies mentioned in our Top Ten list, it found that if comparing women with high HDL versus low HDL, LDL levels didn’t seem to be particularly relevant for cardiovascular mortality prediction. In fact, in women with low HDL, those with high LDL had lower rates of cardiovascular mortality. Combined with the other studies mentioned, this seems to highlight the importance of taking in the “big picture” of all the markers together to get an accurate picture of risk.
The LDL level was a relatively poor predictor of CVD mortality in this cohort of women, with no consistent relationship noted between LDL levels and CVD mortality.
7. Impact of Endurance Exercise on Lipids
The Reason: I always find it interesting to come across a study that mirrors an experiment Dave has already done. Similar to his endurance exercise experiment this likewise showed lipid changes in those undergoing similar exercise – namely a reduction in LDL during the recovery period, as well as a reduction in triglycerides.
LDL + VLDL cholesterol, however, showed a tendency to decrease immediately after the race and was reduced by 17% and 11% of the pre-race level on the following 2 days. Triglycerides were reduced by 30% of the initial level immediately after the race, were still low on the following day, but were restored to normal 2 days after the race.
6. Lipid Level Changes During Exercise
The potential clinical importance of our findings is that evaluation of lipid profiles should be performed carefully since lipoprotein concentrations may not reflect a potentially atherogenic subclass distribution and may be impacted by recent exercise.
5. Ischemic Heart Disease Risk and All-Cause Mortality Modified By HDL and TG In Those On Hypertensive Medication
The Reason: This study was looking at the risk of Ischemic Heart Disease (IHD) mortality in those on antihypertensive medication. They found that the there was no difference in IHD mortality in those who were on hypertensive medication and those with normal blood pressure who weren’t on medication so long as the people taking antihypertensive medication had high HDL and low triglycerides at baseline. Beyond even that, all-cause mortality and death from IHD was increased in those with low HDL and high triglycerides.
Men on antihypertensive medication without TG or HDL-C dyslipidemia at baseline
had no increased risk of IHD mortality compared to normotensive, untreated men. In contrast, men on medication who had one or two dyslipidemias had a clearly increased risk of IHD mortality.
4. A Possible Mechanism Behind High HDL in Alcoholics Explained
The Reason: This one actually caught my attention not only because of the topic of the paper, but also because of its implications beyond the population studied. In short, frequent consumers of alcohol can present with an abnormally high HDL level, and this can eventually progress to high HDL along with high triglycerides. An unusual profile, for sure, and also one that can lead to thinking they’re healthier than they actually are, just by looking at their lipid profile. If you ask them to stop drinking for a while, their HDL goes back to reflecting their normal level. They found, in short, that this was likely due to rapid cycling of VLDL – both increased production, and increased clearance – resulting in higher HDL levels. I found this bit interesting, and perhaps especially relevant in regards to the super high levels of HDL found in Lean Mass Hyper-responders, as well.
Thus, the increased fractional catabolic rate of VLDL triglycerides during chronic intake of ethanol would be well expected to be accompanied by a rise of […] HDL, levels, which decrease again when drinking is discontinued and the VLDL catabolism returns back to normal.
3. HDL Function Beyond Reverse Cholesterol Transport
The Reason: If anyone knows me at all, they know I love the type of research that dives deep into functional aspects of any given particle, or organism. This paper is exactly that, taking a close look at the functional role of HDL beyond Reverse Cholesterol Transport. All too often, HDL is relegated to the particle that “takes cholesterol out of the arteries”, and nothing more. Although RCT is one role HDL has a hand in, it likely has a multitude of functions, including carrying “messages” between cells. I’ve said before that HDL has a managerial role in the lipid system, doing a lot of busywork in the background that isn’t generally noticed or appreciated, and indeed just like a good manager HDL may be far more valuable (and complex) than we realized at first glance.
Although its image has recently taken a publicity hit, HDL still remains a remarkable and highly beneficial factor in the multiple layers of systemic homeostatic control beyond cholesterol metabolism.
2. A Deeper Look at ApoC-III
The Result: Another mechanism paper, taking a look at the functionality of ApoC-III. Although not as frequently discussed as ApoB or ApoAI, ApoC-III is an important signaling protein found on lipoproteins that help regulate triglyceride metabolism, among other things. It’s likely most known for higher levels being related to increased risk of cardiovascular disease, especially as higher levels decrease clearance of lipoproteins from the system. The paper makes the point that insulin resistance may lead to higher levels of apoC-III, so (in my eyes at least) this may point to increased levels potentially having some role in the immune/repair system.
ApoC-III expression is downregulated by insulin […] Thus, in insulin-resistant states, the expression and secretion of apoC-III may be dysregulated.
1. Infection Induced Insulin Resistance
The Reason: While technically not a lipid-related paper, nor a paper I found while on my hunt for #LCCholesterolChallenge related papers, I wanted to include this one for its relevancy to some other topics discussed on the blog. This paper came about from Gabor Erdosi via Twitter, and discusses transient insulin resistance (and hyperinsulinemia) as a result of viral infection. As I’ve discussed previously, insulin resistance may be more than just a response to overstuffed fat cells, but rather may also be induced for signaling purposes as a part of a response to various stimuli. As it so happens, this paper appears to tell the same tale of an orchestrated immune response in the form of insulin resistance and hyperinsulinemia.
Thus, upon pathogen encounter, the immune system transiently reduces insulin sensitivity of skeletal muscle to induce hyperinsulinemia and promote antiviral immunity, which derails to glucose intolerance in pre-diabetic obese subjects.