Update: Recent NMR Results, Cardiovascular Disease Risk, and What I Eat

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.

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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? 

My Diet

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.

Further Testing

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.

References

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.