- What is LDL-C?
- What determines LDL-C levels in the blood?
- Why all the conflicting information on saturated fat and LDL-C?
- Breaking down the Retterstøl study
- What foods increase LDL-C? Key takeaways
- Rule #1 – Avoid Trans Fat (and by extension vegetable oils)
- Rule #2 – choose monounsaturated fats (MUFA) over Omega 6 PUFAs and saturated fats
- Rule #3 – Cholesterol hyper-absorbers/producers may benefit from reducing saturated fat intake
- Rule #4 – Know your PCSK9 Genes
- Rule #5 – Ignore the diet gurus!
- Rule #6 – Experiment with a plant based diet
Perhaps some of you saw this recent study which looked at the impact of a high fat, low carbohydrate (HFLC) diet on LDL-C levels in healthy adults. Overall, the HFLC diet increased LDL-C by 44%, but that wasn’t the biggest takeaway from the study. For me, the big flashing neon message was the incredible variability exhibited between different individuals.
In some subjects, LDL-C only went up 5%, while others saw a 107% spike!
Soak that in for a minute.
This data highlights perfectly our message here at Gene Food: that one size fits all diet advice is pretty much worthless. Based on the fat metabolism and LDL analysis we do for our custom nutrition plans, we have a pretty good idea of how different genotypes will respond to a high fat diet. It’s clear that some of us can eat a diet higher in fat with very little trouble, and others should be in the habit of strictly limiting dietary fats, including vegetable oils, which are the secret killer for many people.
Armed with the knowledge that one’s propensity to see spikes in LDL is driven by genetics, let’s dive into the causes of elevated LDL-C, and what those of us prone to higher lipid numbers can do to bring them down (spoiler alert, a high fat diet won’t be on the menu).
What is LDL-C?
You’ve probably heard of LDL-C in association with blood tests run by your doctor, often called lipid panels. Lipid is just another word for fat. When you go to have a standard “lipid panel” done, doctors are measuring for the amount of certain types of fats in your blood, both animal (cholesterol) and if it’s a good blood test, sterol (plant). Fats can’t dissolve in water, and our blood is mostly water, so special molecules called lipoproteins carry cholesterol throughout the body, just like taxis carry a passenger through a city.
Although it’s been demonized in certain nutrition circles for years (in some cases rightfully so), cholesterol, standing alone, is a good thing. The problem is when cholesterol ends up in a place it shouldn’t, like the wall of an artery. And the only way cholesterol can end up in the wall of an artery is if it is carried there by a lipoprotein taxi.
For a deeper dive into all things cholesterol, I highly recommend Dr. Peter Attia’s excellent series The Straight Dope on Cholesterol.
HDL-C, or high density lipoproteins carrying cholesterol, are said to be the “good type” of cholesterol, because they shuttle cholesterol to the liver, out of the body and away from the artery wall.
LDL-C, or low density lipoproteins carrying cholesterol, are labeled as the bad cholesterol because they have the potential to deposit cholesterol into the artery wall, where the accumulated plaque can then rupture, causing a heart attack. Tests like the calcium score can actually measure the amount of plaque that has built up in the artery, which gives you a picture of how much damage, if any, gas accrued, but that is not what LDL-C tests measure. LDL-C measures how much cholesterol is in your LDL particles. High LDL-C doesn’t mean that any of that plaque has done damage, but the higher the LDL-C is, the greater likelihood that a calcium score would confirm lesions somewhere in the heart.
So, in other words, your LDL-C number gives you an idea of how cholesterol rich your LDL particles are. The reason LDL-C doesn’t give you the full picture is because LDL particles carry both triglycerides and cholesterol, a topic we will cover in more detail in a minute.
What determines LDL-C levels in the blood?
For this part of the post I am bringing in the big guns, aka Aaron.
Thanks John. I want to dive in and explore what actually causes LDL-C levels in the blood.
LDL-C in the blood is determined by two things: its production and removal from the blood.
LDL can actually be produced from cholesterol and dietary fats as shown in the image below, forming from VLDL (very low density lipoprotoeins) which are then converted into LDL.
However, studies show that an increase in saturated fat intake does not significantly alter LDL-C in much of the population (see below). Similarly, increasing polyunsaturated fatty acid (PUFA) intake did not alter LDL synthesis suggesting other mechanisms are at play. Importantly, trans-fat intake was correlated with an increased production of LDL, further evidence that avoiding trans-fats is an important step if you want to bring down LDL-C levels (R).
So if production isn’t a major issue for most people, what about LDL removal from the blood?
Well, as you can see in the image above, LDL (and the cholesterol it is carrying) is absorbed through LDL receptors (LDLR) found on the surface of cells. Interestingly saturated fats were shown to decrease LDLR (R), and also cause changes in the expression of the sterol regulator element binding protein 1 (SREBP1) (R), which led to increased LDL-C in mice following a high fat diet.
Interestingly a high PUFA diet had the opposite effect and led to increased LDLR levels (R).
This teaches us that problems with LDL are often the result of a lower number of LDL receptors, and saturated fat can impede the function of LDL receptors, causing greater levels of LDL in the blood.
So should we replace all saturated fat in our diets with PUFA and MUFA equivalents? The answer depends largely on genetics. For some genotypes, the answer is yes, it will be best to avoid almost all sources of saturated fat, from ribeyes to MCT oil. For others, there is no need to avoid all saturated fat. Some can even thrive on a diet higher in saturated fat. It should also be pointed out that, although there is a link between saturated fat intake and increased LDL-C, there isn’t a strong link between those two factors and an increased risk of heart disease, some of these discussion surrounding LDL-C have more to do with biomarkers than they do health outcomes.
Furthermore, there are major issues with PUFA intake in the typical diet. The goal is to get just as much in the way of omega 3 fatty acids as omega 6 fatty acids, but the balance for most of us is skewed towards the omega 6 side of the spectrum. We should be aiming for a near 1:1 ratio (or as good as possible) of omega-3 (more fish oils) and omega-6 (incorporate nuts and seeds), whereas most are actually strongly shifted towards omega-6 as the result of overconsumption of processed vegetable oils (R). Furthermore, there are issues surrounding possible oxidation of these vegetable oils, which can be worse for your heart than saturated fat. (R) In fact, this NEJM study demonstrates that oxidized phospholipids tend to bind preferentially with Lp(a) particles, which is thought to be part of the reason Lp(a) can be so dangerous.
Why all the conflicting information on saturated fat and LDL-C?
As we’ve seen, the impact of saturated fat is probably governed by the amount of LDL receptor activity in a given individual. Those with a genetic predisposition to have lower LDL receptor activity should probably eat less, or in some cases, very low fat, whereas those with more robust LDL receptor activity can eat more fat. Especially when it comes to saturated fat, there is an all out battle afoot for hearts and minds, with the Vegan and Paleo camps essentially at each other’s throats. Why the conflict and who is right?
It’s possible they both are, it just depends on the person.
The conflicting picture likely arises because of the huge variation in individual responses to eating dietary fat. There are definitely people who are “hyper responders,” meaning they have an elevated reaction to eating saturated fat and cholesterol. Some people will be at much greater risk for heart disease on a high fat diet. Others won’t be. The trick is to figure out whether you are a hyper responder. For example, cholesterol absorption can vary from as little as 20% to as much as 80% of the cholesterol we eat (R). This was further evidenced in the recent study by Retterstøl et al (R) which we cited at the outset of this post.
While that study is small, and so we shouldn’t draw strong conclusions, it is an important first step. High fat diets have been growing in popularity and studies looking at the effects are lacking, especially in generally healthy populations. The take home message is that in those who followed a LCHF diet (5% carbohydrate) LDL-C increased by 44% over three weeks. That’s a dramatic spike.
For the purposes of this post though, the most interesting outcomes occur when you look at the individuals within that LCHF group, as shown in the figure below.
Breaking down the Retterstøl study
Let’s look at some of those individuals.
In the figure above, the blood biochemistry of various factors for the 15 individuals following the LCHF diet was plotted. The top left graph shows the LDL-C outcomes and already you can see significant variation (from 5 – 107% increase in LDL-C). Moving to the right, we can see that this then correlates quite closely with total-cholesterol (TC). Things get more interesting with HDL-C where there is a trend of increased LDL-C matching with HDL-C but it’s not perfect, and then when looking at total triglycerides (TRIG) there is no noticeable trend at all.
So what conclusions can we draw from this?
Well, individual #1 looks like the ideal candidate for a LCHF diet (a non responder or low responder), their LDL-C doesn’t dramatically increase, nor does their TC and their TRIGs actually decreases. In our nutrition matrix, individual #1 would likely fall under the Mosaic, Urban Grazer and Paleo diet types.
Whereas individuals such as 13 and 14 might not be ideal candidates as their LDL-C increases as does their TC (so they may be hyper-responders/absorbers), however, they don’t see a similar increase in HDL-C (LDL:HDL ratio is often thought of as being important for heart health) and individual 14 (but not 13) sees a large increase in their TRIGS. These individuals would have a greater chance of being classified as a Wyoan, Villager or Okinawan diet type in our matrix.
As this is a genetics focused site, our next major questions was did they look at the genetics?
While they looked at a wide panel of genes they did not assess SNPs within these genes, nor did they show the gene expression data for individuals, most likely due to the small size of the study making such interpretations difficult. Interestingly they saw no difference in the gene expression of LDLR either between the control and diet groups, or in the diet group before and after treatment. In fact, the only gene that was differentially expressed was SREBP1 which was elevated in the diet group compared to the control group after the end of the 3 weeks, which correlates with the mouse study discussed previously.
Although the authors didn’t look at LDL-R protein expression, they did measure the expression of proprotein convertase subtilisin/kexin type 9 (PCSK9). This protein has been shown to regulate the degradation of the LDL-R receptors (R) and so may provide some evidence of effect on LDL-R expression. Lipid experts Tom Dayspring and Peter Attia touched on PCSK9 recently on one of their mega podcasts which can be viewed here.
|SNP ID||Risk Allele||Effect on LDL||CVD Risk|
|rs11591147||G||Increased LDL (R)||Increased CVD risk (R)|
|rs28362286||C||Increased LDL (R)||Increased CVD risk, but subclinical (R)|
|rs67608943||C||Increased LDL (R)||Unknown|
|rs72646508||C||Increased LDL (R)||Increased CVD risk (R)|
|rs28362263||G||Increased LDL (R)||Small increased CVD risk (R)|
What foods increase LDL-C? Key takeaways
Ok, me again (John). I am taking back the mic from Aaron to try to land this plane.
With the necessary technical issues addressed above, let’s see if we can’t give you what you want to end the post. And I know what you want, you want me to give you a list of foods to eat and foods to avoid to lower LDL-C. At the end of the day, it’s not really that simple, because it’s becoming more and more obvious that this issue is driven in large measure by genetics.
Having said that, there are some key takeaways for everyone.
Rule #1 – Avoid Trans Fat (and by extension vegetable oils)
Trans fat increases LDL-C in all people. Regardless of genotype, it’s bad for everyone, but avoiding trans fat isn’t as easy as it may sound. Trans fat can be sneaky. Some food that is labeled as free of trans fat, will actually have trans fats. Nutrition labels are only required to disclose trans fat if it is found in levels over 0.5 grams per serving. Did you know that all vegetable oils contain trace amounts of trans fat, it’s just the levels are usually low enough that they don’t need to be disclosed? if you’re a hyper absorber of cholesterol, you’re also very likely a hyper absorber of sterol (the fat in plants). Eating vegetable oil opens you up to:
- Tons of omega 6 fats
- Oxidized fats that are bad for your heart
- Trans fat
As such, if you want to keep LDL low, it is imperative that you avoid vegetable oils, as well as food cooked in vegetable oil. This is a tough task in light of the fact that many restaurants use vegetable oils to cook with, but you can speak up and ask the kitchen what they’re using if you’re truly motivated.
Rule #2 – choose monounsaturated fats (MUFA) over Omega 6 PUFAs and saturated fats
Most people should balance fat intake with a preference for MUFAs Omega 6 PUFA and saturated fats. This means exclude processed grains, factory raised meat, cheap salad dressings and food from restaurants dripping in vegetable oil. Many restaurants “cut” their olive oil salad dressings with a cheap canola oil to keep costs down. Ask your waiter or waitress what you’re getting. Instead, opt for whole plant sources of fat, such as nuts and seeds, avocado, choline rich plant foods like chickpeas, and even small portions of grass fed or pasture raised meat.
Rule #3 – Cholesterol hyper-absorbers/producers may benefit from reducing saturated fat intake
People who have read that dietary cholesterol isn’t absorbed into the blood often take the unfortunate step of equating saturated fat with cholesterol. They are not the same, and the irony is there are very few foods out there which are cholesterol rich and saturated fat poor. Eating foods high in saturated fat, like pork, beef, fatty fish, coconut products, cheese, and some others will cause an increase in LDL-C and LDL-P, especially for the “hyper responders.”
The trick here is to know how your body does with fat metabolism, storage and transport. A test like our LDL panel and custom nutrition plan can give you a good idea of whether you’re likely to be a hyper responder, or you can test for yourself at home with an Everlywell kit. Eat a low fat Vegan diet for two weeks, see what your LDL-C numbers look like. Now, try a diet higher in fat for two weeks. Eat some duck confit, eat some steak. Test again. The degree to which your lipids are out of range is the degree to which you’re a hyper responder. This is a very real phenomenon. If you find your lipids look especially bad on a high fat diet, I would recommend reading John Mackey’s book on plant based nutrition “The Whole Foods Diet.” It’s the most reasonable of the Vegan books I’ve read because it acknowledges that most people can be perfectly healthy eating 10% of their calories from animal products.
Use that book as your template.
Rule #4 – Know your PCSK9 Genes
Certain PCSK9 SNPs “may” predict cholesterol response to LCHF diets. Knowing your status for the markers listed above can help you determine whether you are likely to have an increased risk for heart disease when eating a high fat diet.
Rule #5 – Ignore the diet gurus!
LCHF diets are not for everyone, and the lipid changes reported by the Retterstol study are severe. The 5% carbohydrate diet reported in the study is especially extreme, as evidenced by the following quote:
Seven out of 39 participants discontinued the study due to the non-serious adverse events headache and/or fatigue but there were also two serious adverse events. The cause of the two serious adverse events, myocardiopathy and autoimmune thyroiditis after few days on LCHF diet, remains undetermined despite extensive investigation.
The takeaway here is don’t try a ketogenic diet because your favorite podcast host swears by it. High fat diets may work for some, but others are not genetically suited to this style of eating. Even if acute symptoms don’t develop right away, you could be slowly damaging your cardiovascular health. Make an educated decision based on your genetics and important biomarkers.
Rule #6 – Experiment with a plant based diet
We are not here to claim that everyone needs to be on a plant based diet. However, if you’re reading an article about how to lower LDL-C, it’s likely you or someone you know has been told their lipids are a bit high and they need to come down. As we’ve established in this post, people that find themselves in this situation may have lower LDLR activity which prevents clearance of LDL particles, or your body may be producing VLDL from the cholesterol and fat you eat. In either case, there isn’t as much room to add much more dietary fat into the system because your body is using it to make some bad stuff downstream. It’s these situations where people can benefit from the type of plant based diets advocated for by the Ornish and Esselstyn camps. Love them or hate them, these diets will bring down LDL-C, period. The problem is they are notoriously difficult to stick with. Having said that, if the choice is between a plant based diet and a statin, many people will choose the plants. As a general rule, the Ornish and Esselstyn approach is to treat heart disease patients with a whole foods plant based diet that excludes all oils, nuts, avocados and other foods high in sterols. Dr. Esselstyn has had some impressive results stopping, and in some cases reversing, advanced heart disease. (R)