When I wrote a blog post entitled Lipid Changes on a Very-Low-Carbohydrate Ketogenic Diet about 10 months ago, I knew it would be controversial. Although some people in the low-carb community agreed with my position and conclusions, others thought I shouldn't have revealed my lab results because it would give critics ammunition to use against carb restriction.
I think the jury is still out on the significance of high levels of LDL-C and LDL-P in people following a low-carbohydrate, high-fat diet. My intent is never to offend anyone, and I'm certainly not an expert in this area by any means. But I did want to be 100% honest with people about my own experience and why I wasn't comfortable with those dramatic increases in lipid values. Since writing that post, many ketogenic dieters have contacted me to report similar results and ask how concerned they should be and what they can do to get their numbers moving in the opposite direction. I'm happy to try to help in any way I can, and although I provide information about what has worked for me, I realize that people respond differently to various dietary changes. Also, there are other causes of hyperlipidemia, including major weight loss (1), as well as non-diet-related reasons, such as hypothyroidism.
My follow-up NMR last June revealed improvement two months after making changes to my diet, but I didn't know if my numbers would continue to decline, stabilize, or increase over time. I've been eating a high-fiber, low-carb. lower-saturated-fat diet for about a year, and I recently decided to have another NMR (Nuclear Magnetic Resonance) spectroscopy LipoProfile done to see how things were progressing.
April 2015 NMR results
I'm really pleased with these results. My total LDL-P has dropped by 250 mmol/L and is now borderline-high, as is my LDL-C, which has further declined from 177 mg/dL last June. My small LDL-P has always been low, but it's now less than 90 mmol/L.
Elevated LDL-C, LDL-P, Insulin, and Cardiovascular Disease Risk
How important are LDL-C and LDL-P in terms of cardiovascular disease (CVD) risk? It depends who you talk to. I respect the opinions and expertise of the professionals below and believe they all provide valid arguments.
I asked Dr. Thomas Dayspring to review my most recent NMR report. He feels that although my LDL-P has improved, it still places me at greater than average risk for a cardiac event. He said that given my age and the fact that I'm in the latter stages of perimenopause, I should definitely monitor this and other values and make appropriate lifestyle adjustments as needed. Also, there's no arguing that I carry a lot of cholesterol in my HDL particles as well as LDL particles, and this cholesterol is transferred back and forth between all the particles within the bloodstream. He questioned whether the excess cholesterol is due to hyperabsorption, hypersynthesis, increased lipoprotein production and lipidation, or decreased clearance. Without further testing, there's no way to know for certain.
Dr. Dayspring is a very progressive lipidologist, and I highly recommend his LecturePad presentations (sign up for free, and you'll be able to access all content). In Part 1 of Have Cholesterol Measures Outlived Their Usefulness, he explains the reason oatmeal and other whole grain cereals aren't a good choice to increase fiber intake for most people, why triglyceride levels should optimally be less than 100 mg/dL, and the dangers of relying on LDL-cholesterol measurements to evaluate degree of cardiovascular risk. In Part 2, he discusses the importance of controlling insulin resistance (IR); the interplay between hyperinsulinemia, hyperleptinemia, and appetite; and the benefits of carbohydrate restriction for those with metabolic syndrome: "Dr. Atkins was right."
Although in my other blog post I referred to an article where he recommended statin therapy for anyone with an LDL-C level greater than 190 mg/dL, more recently, he said:
"That was written some time ago. I'd now amend that everyone with moderate to high lifetime risk for CVD events as determined by lipid/lipoproteins, family history, examination (BP, xanthomata) and smoking history - not simply LDL-C by itself."
Dr. Dayspring also provides interesting information in the Cellular Regulation of Sterols lecture series, including the fact that vegans (who consume no animal products and therefore no cholesterol) absorb the same amount of cholesterol from the gut as do meat eaters and lacto-ovo vegetarians (about 55%, on average), but in their case, it's entirely biliary in nature as a result of the gallbladder releasing hepatic cholesterol into the intestine. Even in non-vegans, most of the cholesterol in the gut comes from the bile rather than the food we eat, which is why limiting egg consumption doesn't make sense as a strategy for lowering cholesterol levels. Even people who absorb more cholesterol than average ("hyper-responders") experience only mild elevations in serum cholesterol concentrations when dietary cholesterol is increased (2).
Ivor Cummins is a chemical engineer known on social media sites as The Fat Emperor and is a prolific blogger on his website of the same name. He's spent a great deal of time studying and writing about the role insulin and a high-carbohydrate diet play in CVD risk. While he agrees with Dr. Dayspring that LDL-P count is important, he feels that the combination of small, dense LDL particles and high insulin levels are the root cause of coronary artery disease (CAD) (3). He also believes maintaining adequate vitamin D3 levels is crucial to cardiovascular health, and I've recently seen him advise people with genetic defects (such as ApoE4) and very elevated LDL-P to replace a portion of saturated fat with monounsaturated fat and long-chain omega-3 fats. In addition to blog posts, he has several great videotaped lectures on his website, including "The Cholesterol Cunundrum."
Dr. Peter Attia is a very-low-carbohydrate, ketogenic diet proponent who believes that elevated LDL-P values warrant dietary modification, including reduction in saturated fatty acid (SFA) intake. In a recent blog post, he describes a patient whose LDL-P dropped from 3500 to 1300 as a result of cutting saturated fat intake down to 25 grams per day while remaining on a ketogenic diet. He goes on to say:
"While I believe the population-based guidelines for SFA are not supported by a standard of science I consider acceptable, it does not imply I believe SFA is uniformly safe at all levels for all individuals."
A few years back he wrote a 9-part series of blog posts entitled The Straight Dope on Cholesterol, which received a lot of attention and great feedback. Unfortunately, I've only read the first 2 parts at this point, but I'm hoping to read the entire series soon.
Dr. Spencer Nadolskey is a family physician who promotes a whole foods diet and healthy lifestyle. He's recently done some experimenting with different diets (low-carb and vegan) and reported the changes in his biomarkers with each. He has a very balanced and moderate approach to health and wellness, recognizing the importance of taking people's preferences and individual responses into account when making dietary recommendations.
As I said in my original blog post, most people who follow a low-carbohydrate, high-fat diet don't experience significant elevations in lipids as I did, although it's estimated that at least 25% do. In fact, Dr. Attia states in the blog post I linked to above that even when he was consuming 40% of his calories as saturated fat while following a very-high-calorie ketogenic diet, his biomarkers actually improved.
Increased vs. Decreased Risk for Cardiovascular Disease
ApoE genotype Apolipoprotein (Apo) E is a regulator of plasma lipid levels. I have two copies of the ApoE3 gene (3,3), which carries a low risk for atherosclerosis and cognitive disorders including Alzheimer's disease (4). Those with the ApoE4 genoptye, who often have elevated cholesterol levels and are at increased risk for developing CAD, dementia, and other diseases, may find the ApoE4 Forums Heart Disease Discussion helpful for information and support.
Family history Regardless of genetic markers, a strong family history of heart disease is another risk factor for a cardiac event. Allthough I don't have the ApoE4 genotype or familial hypercholesterolemia (FH), several of my family members have had CAD. My mom, who has stable atherosclerosis, has been on a low-dose statin for over 10 years. She is thin, active, and has never had any markers of insulin resistance (her lipid profile is remarkably similar to my own), although she was a long-term smoker before quitting eight years ago.
BMI and waist-to-hip ratio (WHR) My BMI is 19 (under 23 is optimal), and my WHR is 0.7 (less than 0.8 is optimal for women in terms of cardiac risk).
LDL-P Larger particles are generally considered less atherogenic than small, dense particles. I have very low small LDL-P and borderline-high LDL-P. While some would argue that my large LDL-P poses no concern, it's still higher than what's considered optimal. Also, in a study published after my initial blog post, large numbers of small and large LDL particles were both associated with increased CVD risk when compared with medium LDL particles (5). In addition, the MESA study researchers, who investigated CAD risk in more than 5000 people, reported this finding regarding carotid intima thickness (CIMT or IMT), a measure of subclinical atherosclerosis in the walls of the artery:
"Without accounting for LDL subclass correlation, small LDL and smaller LDL size were associated with IMT but large LDL was not. However, after accounting for their inverse correlation, both LDL subclasses showed highly significant and independent associations with IMT, with a greater difference in IMT per large LDL particle compared with small LDL. Smaller LDL size was no longer significant after taking into account the particle concentrations of the two LDL subclasses and risk factors. Thus, small LDL was a strong confounder of the association of large LDL with subclinical atherosclerosis, which may explain the widely-held view that larger LDL size is less atherogenic (6)."
Triglycerides, HDL-C, and HDL-P Low fasting triglycerides, high HDL cholesterol, and a large number of HDL particles are considered cardioprotective. Fortunately, I meet the criteria for all three. However, per Dr.Dayspring, my HDL-C/HDL-P ratio of 67 suggests potential dysfunction:
"In a recent study, individuals with the highest HDL-C/HDL-P ratios (>53) had a significant 1.5-fold increase risk for atherosclerosis progression compared with individuals with the lowest HDL-C/HDL-P ratio (<41) (7)."
However, at this point we don't really know whether my risk is increased, and I'm comfortable with these values but will continue to monitor them.
Interestingly, 4 years ago, when I was following a low-fat diet with at least 50% of calories from carbohydrate, my triglycerides were 55 mg/dL, and my HDL was already quite high at 79 mg/dL. I think it's safe to say that I'm not inherently insulin resistant.
Insulin levels I've had fasting insulin tested three times within the past three years, and each time my level was between 1 and 2 mIU/mL, which is considered very low ("Normal" ranges from 1 to 10 mIU/mL). Researchers have known about the connection between elevated insulin levels and heart disease risk for decades (8), and Ivor Cummins has discussed this extensively on his blog and in his lectures.
Fasting blood glucose, postprandial blood glucose, and A1c Elevated blood glucose, even at prediabetes levels, causes damage to endothelial cells that greatly increases CVD risk (9). My fasting blood glucose levels are consistently in the 80s, and 1-2 hours after eating, I am always under 130 mg/dL. I have an A1c every 6 months, and it has been 5.1-5.2% for the past 3 years. Prior to going low carb, my A1c was 5.6%, and my postprandial blood glucose values were routinely higher than 160 mg/dL.
Age I'll be 49 this year, and as stated above, I'm transitioning into menopause, when changes in hormones, lipids, and body fat distribution increase CVD risk (10).
Low-carbohydrate diets are clearly beneficial for reducing CVD risk in people with metabolic syndrome and type 2 diabetes (11). But what about people with type 1 diabetes or those like me, who don't have IR but follow a carbohydrate-restricted lifestyle for blood glucose issues, weight control, or simply because they feel better when they eat this way?
I track what I eat in My Fitness Pal most days and have been doing this for over a year. While the nutritional information for the food database isn't completely accurate (as I'm sure anyone who uses it would agree), it does give a good general idea of caloric and macronutrient intake.
Carbohydrates: I eat 30-45 grams of net carbohydrate per day consistently. Carb sources include nonstarchy vegetables, berries, Greek yogurt, cottage cheese, nuts, and dark chocolate.
Fiber: My fiber intake is very high, roughly equal to my net carb intake. A typical day includes half a large avocado, 1 cup of blackberries or raspberries, 2-3 oz unsweetened chocolate or cocoa (more than half the carbs come from fiber), 2 Tbsp flaxseed and/or chia seeds, 3-4 oz nuts, and 4-6 cups of nonstarchy vegetables. Fiber helps lower cholesterol levels yet doesn't appear to compromise absorption of fat-soluble vitamins and other nutrients (12).
Total Fat: According to My Fitness Pal data, my fat intake ranges from 80-100 grams, which is around 50-60% of my caloric intake (I'm usually between 80-90 grams). Monounsaturated fat accounts for the largest percentage, and primary sources are avocado, olives, nuts, and meat. Eating fatty fish like sardines or salmon 3-4 times a week ensures that I get plenty of long-chain omega-3 polyunsaturated fats, including docosahexaenoic acid (DHA), which is anti-inflammatory and believed to be cardioprotective (13).
Saturated Fat: I don't deliberately set a limit, but I generally end up consuming 20-30 grams of saturated fat daily. Although I'm usually on the lower end of that range, this still allows for modest amounts of cheese, half-and-half, coconut oil, butter, and fatty meat.
Protein: I've discovered that I feel best and most energetic with a relatively high protein intake of around 100 grams per day, which is just over 1.75 grams per kilogram body weight.
Am I in ketosis? I rarely check urine ketones anymore, but when I do they're usually trace or negative. Ketosis has never been my goal (aside from the 3-month experiment I discussed in the prior blog post); keeping blood glucose levels and other biomarkers under control, looking and feeling my best, and eating a healthy, well-balanced diet are what's important to me. However, I realize that for some people, ketosis can be beneficial and desirable.
What about having Coronary Artery Calcium (CAC) scoring, a CIMT, or other tests to rule out subclinical atherosclerosis? According to Dr. Dayspring, CAC testing isn't advisable for women younger than 60, who usually get a zero score even if trouble is brewing. He believes that a CIMT can be useful if done correctly.
Here are his recommendations for further testing in my case, some of which I've already had done. I plan to do the rest within the next year or so.
Sterol synthesis and absorption markers
Omega 3 index
Inflammation markers: MPO, Lp-PLA2, hs-CRP
Once per lifetime tests: ApoE, MTHFR genotypes and Lp(a) level (I'm negative for ApoE and MTHFR genotypes but haven't had Lp(a) done yet)
Homocysteine (I received a score of 8 on a scale of 4-15 umol/L when last done 2 years ago)
Vitamin D (50 ng/ml as of February 2015, which is considered within the optimal range)
On Not Taking Sides
I'm a very moderate person. I don't like confrontation and dislike the "us vs. them" mentality. It probably won't come as any surprise that I'm a registered independent and vote Democratic as often as I do Republican (and increasingly frequently for another party altogether). In addition to the experts listed above, I like and respect the diversity of opinions on this subject that have been voiced by many other knowledgeable people, whether or not they're advocates of carbohydrate restriction.
It's generally agreed within the low-carb community that people have different levels of carbohydrate tolerance. So why is it considered heresy to propose that the same might be true with respect to optimal saturated fat intake?
As I said earlier, I think we still don't know enough about what kind of risk elevated LDL-P and very high LDL-C carry in the setting of a very-low-carb diet where other markers improve. Because of this, I choose to eat in a way that allows me to enjoy all the benefits of carbohydrate restriction yet keeps my LDL particle number at a level I feel comfortable with. Some may think I've gone too far in making changes to my diet in order to improve my numbers; on the other hand, I'm sure there will be others who feel I haven't gone far enough, since my levels still aren't considered "optimal." I understand both points, but I have to go with my gut on this one. Ultimately, it's up to you to decide what feels right for you given what we currently know and don't know.
1. Phinney SD, et al. The transient hypercholesterolemia of major weight loss. Am J Clin Nutr. 1991 Jun;53(6):1404-10.
2. Fernandez ML. Effects of eggs on plasma lipoproteins in healthy populations. Food Funct 2010 Nov;1(2):156-60
3. Phillips MC. Apolipoprotein E isoforms and lipoprotein metabolism. IUBMB Life. 2014 Sep;66(9):616-23
4. Lamarche B, et al. Fasting insulin and apolipoprotein B levels and low-density lipoprotein particle size as risk factors for ischemic heart disease. JAMA. 1998 Jun 24;279(24):1955-61.
5. Grammer TB, et al. Low-density lipoprotein particle diameter and mortality: the Ludwigshafen Risk and Cardiovascular Health Study. Eur Heart J. 2015 Jan 1;36(1):31-8.
6. Mora S, et al. LDL particle subclasses, LDL particle size, and carotid atherosclerosis in the Multi-Ethnic Study of Atherosclerosis (MESA). Atherosclerosis 2007 May;192(1):211-7.
7. Qi Y, et al. Cholesterol-overloaded HDL particles are independently associated with progression of carotid atherosclerosis in a cardiovascular disease-free population: a community-based cohort study. J Am Coll Cardiol. 2015 Feb 3;65(4):355-63.
8. Després JP, et al. Hyperinsulinemia as an independent risk factor for ischemic heart disease. N Engl J Med. 1996 Apr 11;334(15);952-7.
9.Maschirow L, et al. Inflammation, coagulation, endothelial dysfunction and oxidative stress in prediabetes - Biomarkers as a possible tool for early disease detection for rural screening.2015 Mar 6. pii: S0009-9120(15)00071-5.
10. El Khoudary SR, et al. Progression Rates of Carotid Intima-media Thickness and Adventitial Diameter during the Menopausal Transition. Menopause (New York, NY). 2013;20(1):8-14.
11. Volek JS, Feinman RD.Carbohydrate restriction improves features of the Metabolic Syndrome. Metabolic Syndrome may be defined by the response to carbohydrate restriction. Nutr Metab(Lond) 2005 ;2:31.
12. Ramprasath VR, et al. Consumption of a dietary portfolio of cholesterol lowering foods improves blood lipids without affecting concentrations of fat soluble compounds. Nutrition Journal. 2014;13:101.
13. Richard D, et al. Infusion of docosahexaenoic acid protects against myocardial infarction.ProstaglandinsLeukot Essent Fatty Acids.2014 Apr;90(4):139-43.
A couple of days ago I received an email from the makers of a soy-based protein bar that began:
"Scientific research continues to show that a plant-based diet is a healthy dietary pattern. In fact, previous versions of the Dietary Guidelines for Americans have emphasized plant-based diets, and the 2015 Dietary Guidelines Advisory Committee appears to be supporting these previous conclusions."
I'd heard this before, after the US Dietary Guidelines Advisory Committee (DGAC) held their third public meeting on the subject this past May. The fourth meeting is scheduled to be held on the 17th and 18th of July, and there's an opportunity to participate online, if you're interested.
It does seem that plant-based diets -- which are usually, although not always, synonymous with vegetarian or vegan diets -- are gaining favor in terms of public perception of their health benefits and sustainability. While I value the contribution vegetables, fruits, and nuts make to our diet, I disagree that most people would benefit from adopting a diet consisting solely of plant foods and have written about this before. And I'm disappointed that low-carbohydrate diets aren't being presented as an alternative at this point, particularly for the many groups of people who would benefit from them.
However, I dislike the confrontational and accusatory messages I've seen from many advocates on both sides in blog posts, comments, and social media sites. I'm passionate about carbohydrate restriction (apparently I'm not supposed to use this phrase to describe myself, but I think it fits), and I get upset when people criticize it and make claims about the superiority of plant-based diets too. But in my opinion, being respectful of the other side -- who are often equally committed to their way of eating -- while letting the evidence in favor of low-carbohydrate diets speak for itself, is the best way to go.
You may have already seen the debate between Dr. Eric Westman and Dr. T Colin Campbell held at the University of Alabama held in the spring of 2013. Both of these men have put many years into researching the effect of diet on various aspects of health. Each strongly believes that his way is the healthiest and most sustainable even though they are quite different. Dr. Campbell's view is that a plant-based, low-protein, low-fat, high-carbohydrate diet provides optimal nutrition, while Dr. Westman favors an eating plan that is very low in carbohydrate, moderate in protein, and high in fat. I encourage you to watch the video if you haven't already, or even if you have. Notice how Dr. Westman seeks to find common ground with statements like "There's more than one way to achieve excellent health," and then goes on to present the large body of evidence --including randomized clinical trials -- supporting carbohydrate restriction for diabetes, metabolic syndrome, and obesity, with early but promising research on ketogenic diets for cancer and neurological disease. I strongly agree with this approach and feel it's what will ultimately allow for more flexibility in the Dietary Guidelines -- specifically, including low-carbohydrate diets as an option.
I'd like to preface this blog post by apologizing for its length, including links to several long articles. Also, for anyone who doesn't know me, I'm a vocal and enthusiastic supporter of low-carbohydrate diets, but I always strive to be balanced in my writing. I'm very nonconfrontational and don't like "getting into it" with people who disagree with me. However, I expect I'll receive plenty of negative feedback from this article because of the controversial topic.
Cholesterol Results From June 2013 through November 2013
My cholesterol levels have always been higher than average. LDL has ranged from 120s-150s as far back as I can remember, long before I began following a moderately carbohydrate-restricted diet back in 2011. In June of last year, I reported my NMR (Nuclear Magnetic Resonance) LipoProfile results after almost a year of consuming a very-low-carb ketogenic diet (VLCKD) containing less than 50 grams net carb per day. I was very happy with these values and frankly a little surprised that I achieved them while eating delicious, satiating foods.
Lipid Profile from November 2013
In November of last year, I had a standard lipid profile done as part of lab work for my annual physical:
Total Cholesterol: 300
My numbers had increased, but I wasn't terribly concerned about the LDL-C, since on a few occasions it had been nearly that high in the past. Seeing a total cholesterol of 300 was a bit troubling, but I knew it was partially due to having extremely high HDL (Apparently high levels of some types of HDL can also be problematic, although I didn't realize this at the time). Looking back, although I wasn't tracking my intake online regularly back then, I'm pretty sure I was eating the same or perhaps a little more fat than when I had the NMR done five months earlier.
Nutritional Ketosis Experiment
At the beginning of January, I decided to experiment with lowering my carb intake further in order to achieve nutritional ketosis. I didn't want or need to lose weight, but after speaking with a few people who'd reported improved mental focus and energy on minimal carbs and ketone levels between 1.5-3.0, I was intrigued. For the record, I felt great prior to this experiment: no symptoms of adrenal fatigue, excellent blood sugar control, lots of energy, good sleep, etc. But was there a possibility I could feel even better in deep ketosis? I'm a curious type, so I decided to try it for a few months. I had a ketone meter but didn't test very often because the strips are ridiculously expensive. But when I did check prior to this experiment (first thing in the morning, the only time I've ever tested), my ketones ranged between 0.4-1.0 mm.
I began tracking my intake on My Fitness Pal, as many of my clients were doing. I lowered my net carbs to roughly 20 grams per day, although total carbs were often still around 50 grams because I ate a lot of avocados, unsweetened cocoa powder, and high-fiber vegetables like cauliflower. However, my consumption of berries dropped from 1-1.5 cups per day to 5 or 6 every morning at breakfast. I tried to keep protein around 70-80 grams daily (I'm 5'8" and 125 lbs, so this isn't all that low), and I ate more fat in order to maintain rather than lose weight. I never drank bulletproof coffee or added lots of butter or coconut oil to my food. But I did eat a fair amount of cheese, cream cheese, ricotta, and moscarpone, and I began using heavy cream instead of half-and-half in my coffee and tea. I still ate vegetables at every meal, although smaller amounts.
I tested blood ketones a couple of times a week in the morning, and results ranged from 1.2-1.8. After 3 months of eating this way, in all honesty, I didn't feel any different. I still felt great, slept great, etc., but I can't say I had more energy or experienced any cognitive benefits. My weight stayed the same, and my blood sugar control remained good. However, my lipids had definitely changed, and not for the better.
Cholesterol Results from April 2014
I had an NMR drawn at the end of April, and this time I'll admit to being more than a little upset when I saw the results:
I ordered this NMR through a different lab, so there are a few additional labs (mainly VLDL related) that weren't included in the one from June of 2013.
I was really surprised by how much my cholesterol had gone up since the prior test. My first thought was that perhaps my thyroid levels were off. (I have hypothyroidism that was diagnosed shortly before I went low carb, but my levels have been stable for the past few years on desiccated thyroid). However, I didn't feel at all hypothyroid and wasn't scheduled to have my thyroid labs re-checked until summer.
"Why Are You Concerned When You Have Such High HDL-C, Low Triglycerides, and Large, Fluffy LDL-C?"
While I've always been comfortable with higher than ideal cholesterol levels, having an LDL-C over 200 is a different story. The highest value I'd ever seen prior to last December was 158, I believe, about eight years or so ago when I was still following a low-fat, high-carbohydrate diet. But as far back as I can remember, my LDL-C was in the mid 120s to 150s regardless of what I ate, and my total cholesterol was never more than 260. My first NMR was the one last year, so I don't know what my LDL-P values were prior to 2013, but I'm assuming they were above the optimal range, although likely not over 1600. You can see that my LDL and total cholesterol each went up about 100 points and my LDL-P increased by 700 points in a 10-month period. My triglycerides even went up somewhat, although 60 is still pretty low. Although it's my understanding that LDL-C in an NMR is measured directly rather than by using the Friedewald equation (maybe a lipid expert can confirm this), when I plugged my numbers into an online calculator that estimates LDL-C, I got exactly the same number as in the NMR report, 221, for the Friedewald equation and 182 for the Iranian formula (The Iranian formula is believed to be more accurate when triglycerides are over 400 or less than 100).
You may be wondering what LDL-P is, since it's not reported in a standard lipoprotein profile and most doctors don't order it. Dr. Axel Sigurdsson does a great job explaining everything you ever wanted to know about it in his post about LDL-P, but I'll try to give a quick summary. LDL-P is a measurement of the number of LDL (low-density lipoprotein) particles in your blood which carry cholesterol, triglycerides, and another type of fat called phospholipids. According to lipidologists (experts in the field of cholesterol and other lipids), LDL-P is the strongest predictor of risk for cardiovascular disease (CVD) and future cardiac events. Total cholesterol greater than 300 and LDL-C greater than 190 are also associated with significant CVD risk. High levels of LDL-C are prone to oxidation, and oxidized LDL has been linked to the development of arterial plaque and coronary artery disease (CAD). Sometimes people have normal LDL-C and high LDL-P or vice versa (the term for this is discordance), but most people with very high LDL-C have high LDL-P as well. These findings are from recent studies, not decades-old research reported by Ancel Keys.
I want to make it clear that this type of dramatic elevation in LDL-C and LDL-P doesn't occur in most people who adopt a very-low-carb, high-fat diet. I've seen estimates that somewhere between one quarter and one third of low-carbers experience this. I've met and read about several who have. Most people who eat VLCKDs see their cholesterol rise only slightly, not at all, or even decrease, remaining within or near the normal range. I've met plenty of folks like this as well. I've also spoken with people who tell me their LDL cholesterol has always been over 200 and didn't really change after switching to a VLCKD. This is in sharp contrast to what happened to me: going from relatively stable LDL-C between 120s-150s to 221 within a very short period of time.
Of course, many things can affect a person's cholesterol levels, including stress, illness, and injury. Aside from familial hyperlipidemia (FH), there are other genetic disorders of lipid metabolism. Some people's livers produce large amounts of cholesterol (hyper secretors), while others absorb a lot of cholesterol from food (hyper absorbers), and some have both of these issues. My past lipid profiles didn't suggest FH, and I haven't been tested to see whether I have increased hepatic cholesterol production or increased intestinal absorption. I assume I'm probably a hyper secretor, since my levels were higher than average even during my 10 years as a low-fat vegetarian who ate a lot of egg whites but very few yolks or other cholesterol-containing foods.
I do have a family history of heart disease on both sides. My maternal grandfather suffered four heart attacks (the last one fatal), and my maternal grandmother also had coronary artery disease (CAD). My dad's brother has had two heart attacks, and his mother had CVD and died of a stroke. My mom has been on statin therapy since she was diagnosed with CAD ten years ago. (I'm not going to debate the risks vs. benefits of statin therapy in this post, but I'm not a big fan except in certain instances.) You may be wondering what kind of diet my relatives followed. Given that they all grew up and spent their entire lives in Switzerland (with the exception of my mom, who immigrated to the US at age 19), they obviously weren't following the Standard American Diet, but they weren't low-carbers either. My grandfather smoked and had diabetes, and my mom smoked for many years, but my other relatives didn't, and all were moderately active. I've never had a calcium scan or a carotid-intima thickness test(CIMT) to check for atherosclerosis but am looking into having these done. Even if they show no disease at this point, my goal is obviously preventing CAD, heart attack, and stroke in the future.
My NMR results indicate I have the large, pattern A type of LDL with a low number of the more atherogenic small LDL particles (small LDL-P). This is definitely a good thing. However, although I've heard large, fluffy LDL characterized as "harmless" and even "protective," I'm having trouble finding convincing evidence supporting this assertion, especially in the setting of cholesterol levels as markedly elevated as mine. In fact, the authors of the Multi-Ethnic Study of Atherosclerosis (MESA) study summed up their findings as follows:
"Contrary to current opinion, both small and large LDL were significantly associated with subclinical atherosclerosis independent of each other, traditional lipids, and established risk factors, with no association between LDL size and atherosclerosis after accounting for the concentrations of the two subclasses."
Subclinical atherosclerosis is the period when changes are happening in the arteries but the hallmarks of atherosclerosis (i.e., plaque and fatty streaks) haven't developed to the point where the disease can be diagnosed.
It's been pointed out that no studies have been conducted on people following VLCKDs who have very high LDL-C and LDL-P levels, and that's certainly fair to say. However, according to many MDs with expertise and/or personal experience in this area, we really don't know whether CVD risk is lower in low-carbers with cholesterol elevations of this magnitude.
What Do The Experts Say About Very High LDL-C and LDL-P?
I studied lipid metabolism in college as part of the coursework required to become a registered dietitian, but I'll be the first to admit that I have no expertise in that area. I think it's important to listen to the experts in this field since they best understand all of its complexities, including the genetic variations that influence cholesterol levels and the development of CAD. Keep in mind that the physicians listed below are all advocates of carbohydrate restriction to some degree.
Dr. James Underberg is a lipidologist and hypertension specialist in New York City who told me that he has seen similar dramatic increases in total and LDL cholesterol in some of his patients following a carbohydrate-restricted diet. One of the interventions he recommends in these cases is replacing a portion of dietary saturated fat with monounsaturated and polyunsaturated fat sources.
Although technically not a lipid expert, Dr. Rakesh "Rocky" Patel is very familiar with current lipid research as a family doctor in Arizona with hyperlipidemia who treats many people with diabetes and metabolic syndrome. He recommends the CarbNite (cyclical low-carb) method for most of his patients and also follows this approach himself. Back in the fall of 2012, he wrote a fantastic blog post entitled Does LDL-P Matter? in which he described improvement in his carotid intima thickness despite a significant increase in LDL-C and LDL-P after switching to a carbohydrate-restricted diet. When I received my NMR results from April, I asked him if we've learned any more about very high lipids in the context of a VLCKD since he wrote that piece. He responded:
"Not really. It really is an understudied issue. Unfortunately, all the trials in the literature involve the Standard American Diet. Really, I think that before we engage in any discussion regarding cholesterol, one has to establish if atherosclerosis is present in any form. So using testing like CT calcium scoring, carotid intimal thickness testing (CIMT), and genomic scoring (Corus CAD, Cardiodx) becomes imperative and certainly provides context to the lipids."
Dr. Axel Sigurdsson is a cardiologist who practices at a large university hospital as well as a private heart clinic in Iceland. In my opinion, his Doc's Opinion blog provides some of the most balanced, easily understood information about lipids and cardiovascular disease online. I described my experience to him and asked for his thoughts. His response:
"I've seen this lipid response (a very high jump in LDL-C and LDL-P) a number of times in individuals who adopt a low carb/ketogenic diet with relatively high amounts of saturated fat. It seems that a certain percentage of people react in this way. In fact, the lipid response to this type of diet may be genetically determined. Of course, we know that high LDL-C and LDL-P are associated with increased risk of CHD (coronary heart disease). However, nobody really knows what it means in this metabolic situation (nutritional ketosis) and to what degree it is associated with increased risk. Some claim it's not, but I think the evidence is lacking for such a conclusion. On the other hand, we also know that many people with high LDL-C and high LDL-P never have CHD. Of course, you may be one of those people. However, it is difficult to ignore altogether the possibility that high LDL-C and LDL-P may increase the risk of atherosclerotic problems."
Lipidologist Dr. Thomas Dayspring wrote an excellent article about a woman who had an experience similar to mine on a low-carb, high-fat diet, although her case involved weight loss as well. The article is available from his Lecture Pad series, and I highly recommend reading it in its entirety. (You'll have to register to view it, but registration is free). Although it may not always seem like it, he's actually quite supportive of carbohydrate restriction, particularly for people with metabolic syndrome. I didn't discuss my case with him, but here are two quotes from that article:
"We now recognize that the cholesterol usually gains arterial entry as a passenger inside of an apoB-containing lipoprotein (the vast majority of which are LDLs) and the primary factor driving LDL entry into the artery is particle number (LDL-P), not particle cholesterol content (LDL-C)."
"Could the low-carb crowd be outliers and in them we can ignore LDL-C and LDL-P? The advocates of those diets say there is no study showing harm of elevated LDL-P and LDL-C in patients who have eliminated or drastically reduced their insulin resistance and inflammatory markers by low carbing. That is true, but what they want to ignore is that there is no data anywhere that shows they are an exception. Their belief is that by reducing all other atherosclerotic risk factors and normalizing their arterial wall and endothelial biology, that apoB-containing lipoproteins like LDL cannot enter the arterial wall. Although LDL-C and LDL-P in plasma are high, none of the cholesterol content of the apoB particles gains entry into the arterial wall. Is that plausible??? Sure! But is that also erroneous or wishful thinking? Sure? Does one want to bet their CV health or life on a plausible theory? Some do and some do not. Seems to me the first step is to do what this woman did: adjust the nutritional regimen."
He also states that when ketone bodies are present in excess, they can enter the cholesterol synthesis pathway, thereby increasing serum cholesterol levels.
While I agree with Dr. Dayspring on several issues, I disagree with his position (stated in another great article, Understanding the Entire Lipid Profile) that cholesterol-lowering medication is indicated for everyone with LDL-C greater than 190. I think nutritional intervention should be tried first, as it seems to be effective for at least a portion of people willing to do it.
Some of you may have seen spikes in cholesterol similar to mine after being on a low-carbohydrate, high-fat diet for a short period of time or possibly after a few years. You may not be that concerned, and I can understand that given the many positive effects LCHF can have on health, including certain cardiac risk factors. I also think there are still a lot of unanswered questions regarding the risk of elevated cholesterol in the setting of low insulin levels and optimal blood glucose control. But based on the evidence we do have, along with my strong family history of heart disease, I just wasn't comfortable with my numbers. And although I haven't seen this happen in any of my clients yet, I'd definitely recommend some sort of dietary intervention for them if it occurs in the future.
Dietary Changes and NMR Results from June 2014
Over the past two months I made a few small but significant changes to my diet in an effort to lower my cholesterol levels:
1. I cut back on saturated fat, particularly dairy fat and coconut oil, which contain the types of saturated fatty acids with the greatest potential to raise cholesterol.
2. I increased protein back to my previous intake of about 100 grams per day.
3. I doubled my net carb intake from 20 grams to 35-45 grams per day.
4. I began having chia seeds almost every day.
5. I ate sardines 4-5 times a week.
I still eat plenty of saturated fat, including some dairy fat. I drink coffee and tea with half-and-half (only 1 gram of carb in 2 Tbsp), always order Insalate Caprese made with fresh mozzarella at Italian restaurants, and continue to eat eggs cooked in a little butter for breakfast every other day. I still have burrata, ricotta, and moscarpone occasionally and continue eating red meat about 3 times a week. My total fat intake now ranges from roughly 80-100 grams per day, which is about 50-65% of my total caloric intake. That's still a LCHF diet! And in my case, it's also a mildly ketogenic one, since when I've checked my ketones in the morning (again, I only do this sporadically), they've been 0.4-0.8. Personally, I don't see the need to be in ketosis for my own health; to control my blood glucose, I eat a low-carb diet which just happens to be ketogenic. My weight hasn't changed (which was my goal), energy levels are good, sleep is excellent, etc.
I just received my new NMR results from labs drawn earlier this week:
My LDL-P and LDL-C are still higher than I'd like, but they've dropped considerably in a short period of time. I'm especially impressed by the 44-point drop in my LDL-C. My HDL decreased a bit as well but is still quite high. Considering this occurred in less than two months, I'm pretty happy with these results and hope they continue to improve until they return to the "Above Optimal" to "Borderline" ranges, which I consider normal for me.
As I said at the beginning, I'm a strong proponent of a low-carbohydrate lifestyle. I don't think that's ever going to change. But I feel it's important to look beyond the benefits and address the changes in lipids some people experience that could potentially have adverse effects. This was an n=1 experiment, of course. Remember, most people won't experience extremely high cholesterol levels on a VLCKD. But for me and others who do, I don't believe in shrugging it off and dismissing the results of studies because their subjects weren't following a carb-restricted diet. As a dietitian, I just can't say, "Go ahead and eat as much butter, cream, and bacon as you want. It doesn't matter how high your LDL-C and LDL-P are as long as you're eating low carb and your other markers are low," even if that's what many want to hear. Because we just don't know at this point. Maybe one day there will be evidence demonstrating that VLCKDs are cardioprotective even in the setting of significant hyperlipidemia. I truly hope that's the case. But in the meantime, I'm going to eat a low-carb diet that keeps my lipids in a range I feel more comfortable with.
1. Otvos JD, et al. Clinical Implications of Discordance Between LDL Cholesterol and LDL Particle Number. J Clin Lipidol. 2011 Mar-Apr;5(2):105-13
2. El Harchaoui K, et al. Value of low-density lipoprotein particle number and size as predictors of coronary artery disease in apparently healthy men and women: the EPIC-Norfolk Prospective Population Study. J Am Coll Cardiol. 2007 Feb 6;49(5):547-53
3. Cromwell WC, et al. LDL Particle Number and Risk of Future Cardiovascular Disease in the Framingham Offspring Study - Implications for LDL Management J Clin Lipidol. 2007 Dec;1(6):583-92
4. Mora S, et al. LDL particle subclasses, LDL particle size, and carotid atherosclerosis in the Multi-Ethnic Study of Atherosclerosis (MESA). Atherosclerosis 2007 May;192(1):
5. Waterworth DM, et al. Genetic variants influencing circulating lipid levels and risk of coronary artery disease. Arterioscler Thromb Vasc Biol. 2010 Nov;30(11):2264-76
6. Moriel P, et al. Lipid peroxidation and antioxidants in hyperlipidemia and hypertension. Biol Res. 2000;33(2):105-12
7. Ohlsson L. Dairy products and plasma cholesterol levels. Food Nutr Res. 2010 Aug 19;54
8. Mensink RP, et al. Dietary saturated and trans fatty acids and lipoprotein metabolism. Ann Med. 1994 Dec;26(6):461-4
The latest guidelines on treatment of diabetes, prediabetes, and cardiovascular disease published by the European Society of Cardiology (ESC) in collaboration with the European Association for the Study of Diabetes (EASD) are extremely comprehensive (48 pages) and contain over 500 references. Much of the discussion focuses on cardiovaascular risk factors and treatment, although a fair amount of time is spent on diabetes management itself. I'll confess that I didn't have time to read the entire document and certainly don't expect you to, but I did read the short section entitled "Prevention of cardiovasclar disease in patients with diabetes," paying particular attention to the "Diet" section. To say that I was disappointed with the recommendations would be an understatement.
A few quotes from the paper:
"Carbohydrates may range from 45-60% of total energy. Metabolic characteristics suggest thta the most appropriate intakes for individuals with DM are within this range. There is no justfication for the recommendation of very-low-carbohydrate diets in DM."
On the contrary, there are many studies (cited in previous blog posts, most recently this one), along with anecdotal evidence from thousands of people with diabetes, demonstrating that VLCKDs can dramatically improve glycemic control to the point that diabetes medication can be significantly reduced or even eliminated in the case of T2 diabetes.
"Total fat intake should not exceed 35% of energy. For those who are overweight, <30% may facilitate weight loss."
Restricting fat to these levels guarantees that the diet will be high in carbohydrate, which does not benefit people with diabetes regardless of their weight.
"Saturated and trans-fatty acids combined should be <10% of total daily energy intake. A lower intake of <8% may be beneficial if LDL-C is elevated."
Grouping saturated and trans fats together is extremely misguided. One is highly processed and has been shown to cause a number of health problems, while the other is a healthy, natural fat that people have been consuming for thousands of years.
"Vegetables, legumes, fruits, and whole-grain cereals should be part of the diet."
I agree with vegetables and certain fruits being appropriate for people with diabetes, but there is no reason to consume legumes or whole-grain cereals, as they don't contain any nutrients that can't be found in other foods.
Last week I did an interview on TuDiabetes about carbohydrate restriction for people with diabetes where I discussed these issues in more detail, among others, in response to questions from the audience. Feel free to give me any feedback, positive or negative, if you're able to watch. I apologize for sitting so close to the camera that my face pretty much takes up the whole screen and really looks pretty strange, but I'm new to this videotaped live interview thing.
Also, here's a link to my most recent Answers.com articles on a few low-carb breakfast ideas I discussed in the interview.
One of the questions that comes up repeatedly for me -- from colleagues as well as friends -- is whether following a low-carbohydrate, high-fat diet could be detrimental to heart health. A chief concern is that eating foods high in fat, particularly saturated fat, will raise cholesterol levels, thereby increasing the risk of atherosclerotic heart disease. It doesn't really surprise me; after all, for more than 30 year fats have been considered the primary food we should all be cutting back on if we want to avoid coronary artery disease. The USDA's Dietary Guidelines for Americans and My Plate promote whole grains, nonfat milk, fruits, and other foods that are high in carbohydrates and low in fat as a way of decreasing cardiac risk. On the other hand, there is a large body of research showing that lowering carb intake and increasing consumption of fat (both saturated and unsaturated) can result in favorable changes in serum lipids.
Below are a some of the cardioprotective benefits of low-carbohydrate, moderate-protein, high-fat diets:
1. Significant decrease in serum triglycerides. Carbohydrates are a potent stimulator of hepatic triglyceride synthesis and plasma concentration, particularly in the presence of insulin resistance. Lowering carbohydrate intake can reduce triglyceride levels, resulting in lower cardiac risk.
2. Increase in HDL cholesterol. Higher fat intake is positively correlated with improvements in HDL levels, and high HDL cholesterol is considered cardioprotective.
3. Improvement in LDL particle size, glycation, and oxidation. While triglycerides levels almost invariably decline with carbohydrate restriction, LDL cholesterol response appears to be more individualized. LDL has been classified as the "bad" cholesterol for years, and elevated levels are often seen as increasing one's risk of arterial plaque formation and heart disease. However, simply looking at the amount of serum LDL itself gives us very little information about cardiac risk. It is primarily when LDL is oxidized and its particle size small that this lipoprotein becomes most problematic. Restricting carbohydrate intake has been shown to reduce glycation and subsequent oxidation of LDL. A lower-carb, higher-fat diet tends to produce an increase in LDL particle size (known as Pattern A), whereas an abundance of dietary carbohydrate typically results in smaller, denser particles (Pattern B) that increase the likelihood of atherosclerosis.
I also often hear, "If people don't eat whole grains and legumes, how can they consume adequate fiber?" Fiber, particularly the soluble type, has many health benefits. A low-carb diet can easily supply sufficient fiber if it contains plenty of nonstarchy vegetables, nuts and nut butters, seeds, berries, and avocados. Technically a fruit, an average avocado contains about 12 grams of fiber, as well as 16 grams of monounsaturated fat.
As a registered dietitian, I can't endorse a low-carbohydrate diet consisting of 6 eggs fried in butter with 4 slices of bacon for breakfast, 3 hamburger patties for lunch, and a 20-oz steak with a tiny green salad for dinner. While certainly nearly carb-free, it's missing a lot of beneficial phytochemicals found only in plant foods and contains only a couple of grams of fiber. But I firmly believe that a carbohydrate-restricted plan that includes the high-fiber plant foods listed above can be a very heart-healthy way to go.
1. Tay, J., et al. Metabolic effects of weight loss on a very-low-carbohydrate diet compared with an isocaloric high-carbohydrate diet in abdominally obese subjects. J Am Coll Cardiol, 2008. 51:59-6
2. Volek, J.S., et al. Dietary carbohydrate restriction induces a unique metabolic state positively affecting atherogenic dyslipidemia, fatty acid partitioning, and metabolic syndrome. Prog Lipid Res, 2008, doi: 10.1016/j.plipres.2008.02.0033.
3. Hayek, T, et al. Dietary fat increases high density lipoprotein (HDL) levels both by increasing the transport rates and decreasing the fractional catabolic rates of HDL cholesterol ester and apolipoprotein (Apo) A-I. J Clin Invest, 1993; 91(4);1665-16714.
4. Siri-Tarino, P.W., et al. Meta-analysis of prospective cohort studies evaluating the association of saturated fat with cardiovascular disease. Am J Clin Nutr doi: 10.3945/ajcn.2009.27725
Franziska Spritzler, RD, CDE