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Jul 03

Are you a Lean Mass Hyper-responder?

One of the benefits of establishing this niche in Low Carb Cholesterol Research is that I get people sending me their labs constantly. Naturally, I obsess over possible patterns with hyper-responders.There’s one pattern that is clearly emerging that I’m calling a Lean Mass Hyper-responder. (LMHR)

General Hyper-responder vs Lean Mass Hyper-responder

I consider a hyper-responder (like myself) as anyone who sees a dramatic rise in their LDL cholesterol after adopting a low carb diet. Usually, this is 50% or more. As is typical for a low carb diet, most people see their HDL go up and their triglycerides go down.

However, a Lean Mass Hyper-responder takes this to a new level. I consider the cut points as follows:

  • LDL-C 200 mg/dl (5.2 mmol/l) or higher
  • HDL-C 80 mg/dl (2.1 mmol/l) or higher
  • Triglycerides 70 mg/dl (0.79 mmol/l) or lower

Note these are just the starting ranges. Typically I see both LDL-C and HDL-C hit levels no one else has, while likewise having very low Triglycerides. Here are some examples:

LDL-C HDL-C TG
431 147 46
226 98 52
342 110 61
263 89 55
277 102 67

This is only the first five I found to plug into this post. I suspect I probably have at least another half dozen or more that I’ve responded to on Twitter, email, or comments here at the site.

In fact, the very first LMHR I encountered was Nicole Recine here on the comments of a blog post. I’ve since collaborated with her quite a bit and consider her a damn awesome resource for low carb. (See her site at NicoleRecine.com) She’s sub-10% fat mass, very energetic/althletic, and much more comfortable standing than sitting. She holds at an extremely high LDL-C of 558 with an HDL-C of 140 (Total Cholesterol of 721). Yet, like me, she gets frequent checkups such as the CIMT that continue to show normal results.

Characteristics of a Lean Mass Hyper-responder

As the name suggests, LMHRs tend to be on a very low carb diet while also lean and/or athletic. Some are ultra-athletes and have taken strongly to the low carb way of life with great appreciation. And of course, all of them are shocked to see their cholesterol scores at these levels. Yet there’s clearly a mechanistic reason for this…

A Simple Theory

For me, this certainly has an Occam’s Razor-level explanation. Before reading below, be sure you at least know your basics with my Simple Guide to Cholesterol on Low Carb series.

Lean and/or athletic low carbers have three things in common:

  1. Lower adipose stores (less body fat energy) relative to the average peer.
  2. Lower glycogen stores (less incoming dietary carbs) relative to a carb-centric diet.
  3. Higher energy demands.

Our body seeks to keep our glycogen stores in our liver and muscles reasonably stocked, even on a low carb diet. But obviously, this is more of a challenge when you are both lowering dietary carbs and burning through it at a faster rate than most. Per Volek and Phinney, the body gets better at sparring (and I have my own data that confirms this), but the demands are still relevant for available fuel.

So think about it — (1) lower adipose fuel tank, (2) lower glycogen fuel tank, yet (3) higher energy demands. It makes perfect sense for the body to want to mobilize more fat-based energy to meet the need. And yes, that will ultimately mean more VLDL particles (VLDL-P) delivering more triglycerides to the cells, ultimately remodeling to LDL particles (LDL-P). Likewise, this means more of the cholesterol in those boats (LDL-C) being circulated along with them.

This explains why both LDL-P and LDL-C would be higher, while TGs would be remarkably low, relatively. The TGs are getting depleted from use, yet there’s no denying that more “boats” (LDL-P) are needed to provide them.

Likelihood for Children on a Low Carb Diet

This needs to get talked about as soon as possible. If this mechanism is indeed true, I’d hypothesize many children going on a low carb diet would likewise exhibit signs of a LMHR given higher metabolic rates relative to adults. Indeed, there have been three cases I’ve been made aware of in the last couple months. One privately shared via email, one in the comments of this site, and one on the forums of another. In all three cases, the child fits the pattern of an LMHR.

Naturally, this means many children could be incorrectly diagnosed as having Familial Hypercholesterolemia. Again, FH is, in fact, a genetic disease. That it often gets diagnosed on cholesterol scores alone is a modern tragedy. My fear is that this will happen more often as low carb diets become more popular and GPs don’t know enough about cholesterol and the lipid system to understand what is happening in this context.

 

Final Thoughts

All things considered, I hope the theory proves true given it makes a lot of sense. Before this particular pattern emerged from having lots of labs to compare to each other, I often speculated a higher mobilization of LDL-P could be used by the body as an “alternative glycogen store”. This profile adds some weight to this possibility.

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George Henderson (@puddleg)
Guest
This makes sense to me. It’s been theorised that SGLT2 inhibitors, used in the treatment of diabetes, increase LDL by increasing fat trafficking. They don’t cause an increase in MIs and do reduce deaths from heart failure and kidney disease significantly. “These data suggest that empagliflozin, by switching energy metabolism from carbohydrate to lipid utilization, moderately increases ketone production and LDL cholesterol levels.” https://www.ncbi.nlm.nih.gov/pubmed/27207551 These drugs are keto diet mimics across a range of effects, including natriuresis. It’s also possible natriuresis itself contributes to LDL elevation, as low salt diets increase LDL https://www.ncbi.nlm.nih.gov/pubmed/1921253 Interestingly cholesterol synthesis itself is via HMG-CoA… Read more »
Thein
Guest

I am 43 yrs old, in low carb for one yr. But more liberal LCHF. I am 175cm, weight fluctuate 59kg to 61kg. (was 65kg before LCHF).
Last year Nov, blood test:
HDL 76 mg/dl
LDL 220 mg/dl
Tri. 54 mg/dl.

Yip
Guest

I am 50, male, did a blood test in January 2018. Weight 69kg, 175cm
HDL: 73 (2016: 61)
LDL: 175 (2016: 121)
Trig: 60 (2016: 57)

My doctor freaked out on the LDL scores. I lost 11kg over 3 years, lost 3″ in the waste and 1″ around the neck. He told me to stop my diet before he has to give me statins to control the LDL. Doctor did admit that all my other medical markers are fine, he does seem confused.

Siobhan Huggins
Admin
I went ahead and calculated your total cholesterol and then put it into our report tool – –==== CholesterolCode.com/Report v0.9.2 ====– … on – ::: … Total Cholesterol: 260 mg/dL 6.72 mmol/L LDL Cholesterol: 175 mg/dL 4.53 mmol/L HDL Cholesterol: 73 mg/dL 1.89 mmol/L Triglycerides: 60 mg/dL 0.68 mmol/L –CHOLESTEROL REMNANTS– Remnant Cholesterol: 12 mg/dL 0.31 mmol/L >>> Lowest Risk Quintile Remnant Chol to HDL: 0.16 >>> Lowest Risk Quintile Go to https://tinyurl.com/y8hokam2 for more on Cholesterol Remnants –ATHEROGENIC INDEX OF PLASMA (AIP)– AIP: -0.444 >>> Lowest Risk Third Go to https://tinyurl.com/ycccmmnx for more on Atherogenic Index of Plasma –CONVENTIONAL… Read more »
Craig
Admin
Very interesting. It appears I’m a LMHR, too. The best theories are those that simply explain the observations, are falsifiable, and make testable predictions. I was thinking about what some those tests might be. If we have a LMHR, removing any one of the of the three pillars should decrease LDL-P LDL-P should be decreased by: 1. Gaining 10 pounds of body fat (then readapting to LCHF). Might be possible to test with someone who’s weight fluctuates with cycles of feasting / fasting or strict LCHF / normal diet. 2. Filling the glycogen stores of the liver by carb loading.… Read more »
George Henderson (@puddleg)
Guest
Also have a look at this https://www.ncbi.nlm.nih.gov/pubmed/8304441 ” Two days of fasting caused a reduction in body weight with an approximately 40% decrease in the epididymal fat depot and fat cell size. No changes in serum cholesterol were noted, but serum triglycerides fell approximately 55% with fasting. LDL receptors detected by immunoblotting decreased progressively with fasting to levels that were 95% below controls in adipocytes isolated from epididymal fat pads by 2-3 days. In contrast, hepatic LDL receptor expression was unaltered by fasting. After 2 days of fasting, the rate of synthesis of LDL receptors in isolated adipose cells was… Read more »
James
Guest

Is the LDL conversion you give correct? I think 200 mg/dl is 5.2 mM (mmol/l).
I cycle 100 km or 200 km (up to 10 hour ride) at least once a week on an empty stomach. I closely follow a very low carb diet for two years. Anyway, my results are broadly in keeping but I’m not so lean (bmi 24).
Trig: 0.8 mM
HDL: 1.5 mM
LDL: 6.3 mM

Bill
Guest
I have your top HDL beat. None of my docs has ever seen anyone even close. Latest lipids (roughly consistent over many years): LDL 199 (calculated) HDL168 TG 38 Fasting insulin 2 (“normal” lab range 2–14) I eat moderate low carb, intermittent fast (no breakfast), and do very brief but extremely high intensity strength training 2x/week. Otherwise no athlete, though resting heart rate at 59 is 45. I am lean though certainly not ripped, maybe 10% body fat. I have resisted the temptation to get an advanced lipid panel since I really don’t know what I could reasonably do with… Read more »
George Henderson (@puddleg)
Guest

Hi Bill, you can have high HDL for genetic reasons, such as a CETP defect – and whether this is good or bad for you depends on your insulin level.
So, you are doing fine.

https://www.dropbox.com/s/glpf1xe75coi1jk/Healthy%20HALP.pdf?dl=0

Bill
Guest
Thanks, George. I should have mentioned that, indeed, high HDL (and my lipid profile in general) does seem to run in my family even though none of them eat or exercise like I do. However, their pattern is far less exaggerated than mine. So I’d guess that, as you suggest, some of my profile is genetic, the rest resulting from some combination of low carb/intermittent fasting/high intensity strength training. I’m still not convinced anyone really knows what it all means for CVD risk (aside from various modest correlations of unknown causal significance and possibly highly context dependent). Luckily my doc… Read more »
OobLaDee
Guest
I’m so glad to have found you, Dave! I’m a 74 year old male, but I do still fit the lean, athletic, LMHR profile. My recent NMR results: HDL- 82, LDL- 202, Trig’s- 59, aligning about perfectly with your cut points. I assumed my body had good reason for the out of whack numbers, but I’m relieved, thanks to you, to find they’re not uncommon. I eliminated all grains and sugars 2 years ago, and for months now I’m all out keto. I abused my body for 45 years with a heavily grain based vegetarian diet and ended up with… Read more »
Tim
Guest

Hi Dave.

Been following your work with interest.
This last post is especially germane.

I almost fit the profile, (LDL extremely high, HDL a little lower than your cut and trigs a little higher, intensive exercise). I am almost 70. When I get tested I will send my results for your database.

Logic makes a lot of sense and answers questions I have had for years.
Keep up the good work.

Tim.

Sabine
Guest
Hi Dave, 44-year old athletic female coming out of the woodworks 🙂 Your hypothesis makes a lot of sense to me. I lift weights, do pilates, barre, and a lot of body weight training, and kick and punch the crap out of bags. I have been low carb for a while, but recently I have been leaning toward the very low carb end of things. With 132 lbs at 5’7″ I am lean. Had the lipid NMR done a couple of times. The last one definitely puts me in the lean mass hyper responder category (from memory): LDL 200 HDL… Read more »
George Henderson (@puddleg)
Guest
More evidence – huge increases in LDL cholesterol after a 7-day fast http://jn.nutrition.org/content/129/11/2005.full “Fasting increased total serum cholesterol from 4.90 ± 0.23 to 6.73 ± 0.41 mmol/L (37.3 ± 5.0%; P < 0.0001) and LDL cholesterol from 2.95 ± 0.21 to 4.90 ± 0.36 mmol/L (66.1 ± 6.6%; P < 0.0001). Serum apolipoprotein B (apo B) increased from 0.84 ± 0.06 to 1.37 ± 0.11 g/L (65.0 ± 9.2%; P < 0.0001). The increases in serum cholesterol, LDL and apo B were associated with weight loss. Fasting did not affect serum concentrations of triacylglycerol and HDL cholesterol." Even though fasting… Read more »
George Henderson (@puddleg)
Guest

And here we go – the same length fast in obese subjects lowered LDL.
So there is definitely a “lean high LDL” phenotype for some reason when burning fat.

http://www.kuuroorddeschouw.nl/images/Publicaties/Onderzoek_obese.pdf

Tim
Guest
Dave, Great information. I am a 54 yr old male. Went low carb and had the following lipid results: LDL 304 HDL 91 TG 78 This occurred when I was initially losing weight 206 lbs to 190 lbs over an 2 month period. I am also fairly lean and Weight train ~5x week during this time which I have been doing for many years. Become very concerned and Cut back on sat fats and added small amounts of carbs. Lipid profile change as follows two months later: LDL 135 HDL 95 TG 59 Did not feel as good so reduce… Read more »
Joseph
Guest

I am on zero carb meat only diet since 5 months. Age 60, height 166 cm, weight stable at 55 kg. On completing 45 days (03-04-2017) on the diet my lipids were as follows.
TC: 446
TG: 205
HDL: 61
LDL: 344
On completing 90 days (17-05-2017) on the diet as follows.
TC: 673
TG: 69
HDL: 104
LDL: 555
Any comments please!
Thank you.

Mike Broadley
Guest

Hi
58yr old male.
Weight 83.5 kg – was 95kg 3 years ago. Very active 6/7 days per week. Weights and HITT.
LCHF 3years
16:8 Fast on daily basis
Blood draw done fasted.
VLCHF 6months
Cholesterol 10.1
Trig 0.8
HDL 2.5
LDL 7.2
TC:HDL 4

Never felt better

Carlos Lacayo
Guest
Dave, Last November (before Keto) I found out I had High Cholesterol and Doctor put me on Atorvastatin. Please see Bloodwork 1. Choleterol: 280 Tryglycerides: 64 HDL: 89 VLDL: 13 LDL:178 February got checked again (still before Keto) see Bloodwork 2 Cholesterol: 252 Triglycerides: 54 HDL 83 VLDL: 11 LDL: 158 At the beginning of May I discovered Keto because I had trouble loosing body fat for years. Keep in mind that I am a very active person (for the last 10 years) with weights, and cardio 4-5 a week. 2 months in Keto have changed my everyday lifestyle. My… Read more »
Carlos Lacayo
Guest

I also want add that after being fat adapted for a month (beginning of June) I applied intermittent fasting 16/8. Fasting really kicked my Keto into gear especially at the gym.

Thank you for all that you’ve done and I think it’s amazing how you are helping people discover this mystery. I will definitely be donating to you buddy.

Tim Newton
Guest
Hi Dave Here’s another from the UK from a 66 year old marathon runner (10th fastest in UK this year!), 2 yr 6 months LCHF. I’m frequently in ketosis: 3.1 after a recent long run. Numbers in mmol: TC: 8.05 Trig: 0.71 HDL: 2.94 LDL: 4.78 TC/HDL 2.74 Weight 9st 1lb (127 pounds) BMI around 18/19 I had the blood test recently as part of the 5 yearly NHS healthcheck for us oldies. The GP called me in when he saw the figures and immediately opened the question of statins! I quickly disabused him, as politely as I could (not… Read more »
Matt Remine
Guest

Hi Dave,

47M/5’5″/137lbs 14%BF Zero Carb for 3 months at time of test. 18hr daily fasts. High output daily workouts/cardio/labor in trades.

TC 471
HDL 80
Trig 88
LDL 373

Hope that helps. Thank you for all of your work.

Yas
Guest

Dave

I am a 50 years old full marathon and an ultra marathon runner.
LCHF 7~8years. Height 162 cm, weight 53~54 kg.(before LCHF weight 73kg)

LDL 261
HDL112
TC 420
TG 31
Fasting insulin 2.7

Your work is very very interesting.
I also want to know what is happening?

Keep up the good work!

Sietske
Guest
Hi Dave, I’d like to add a datapoint for you. It’s my husband, they diagnosed his as FH last year purely based on his lipid profile and told him he could come back for a staton prescription or not at all. No option for further testing. Not even genetics! He didn’t go back for statins, no way he’ll ever take them! FH or CVD doesn’t run in his family at all, but unfortunately we have no tests from before our LowCarb lifestyle. We suspect he’s a LMHR but we cannot be for sure. Your work is very interesting and reassuring,… Read more »
Sietske
Guest

Last sentence scrambled up! Should be “… second test, then he’ll do the ED protocol.” Oh, and forgot to mention; 42 years old male. And its now two years ago that we got those numbers and diagnosis, not last year. Time flies!

Ryley
Guest

Hi Dave,

Total cholesterol 6.4mmol/L
Ldl 4.53
HDL 1.74
Tri 0.38
Body fat around 8%
Waist size 28″
I’m 23 5’7 143lbs and would say I’m very active
Warehouse job + working out and sports
Been LCHF for 7 months with a weekly cheat day

Shaq
Guest

Adding to your list:

54 years old
6′ 7″, 210 pounds
Desk job, daily fast of 10+ hours (although some heavy cream in coffee – not sure if that ruins the fast).
Mostly lift weights, some walking. Read about myocardial fibrosis in endurance athletes and dropped running.
I’m not a perfect fit for your definition, but:
Total Cholesterol: 254
Direct LDL Cholesterol: 176
HDL: 83
Triglycerides: 41
Happy to provide other data if helpful.

catherine
Guest
Hi! I wanted to offer my stats as well. I was referred to you by the Ketogenic Diet Open Discussion site on Facebook. I’ve been following a keto diet for the past year and had blood work done with these resulting numbers. I am 52, weight is 135, height is 5’6″. I don’t consider myself a lean endurance athlete by any means, but I hike at least once a week and do HIIT on average about 3X per week. My job varies in terms of physical activity from sedentary to potentially walking several miles a day. But I would say… Read more »
George Henderson (@puddleg)
Guest
I’ll give a little n=1 anecdote here; my chol was always a bit high, as far as I remember, despite having Hep C geno 3, which was a good thing at that time. Clearing HCV and being low carb, it is now significantly higher, within the pattern you describe. I’m naturally lean, exercise a bit but not intensely, practice IF to some extent. After a very high lipid test, I decided to replace butter with olive oil, cheese with avocado, as far as possible for a month or two. Next test, my total C and LDL were the highest they’ve… Read more »
Tim
Guest
Hi Dave. There is a mechanism involving triglycerides and apoB protein release and catabolism in liver that may partly explain your LMHR group. Trigs are the prime control factor in apoB metabolic channeling. They essentially divide LDL into an atherogenic and non atherogenic pool, with a switching mechanism dependent of the trig level. There is a U shaped curve in LDL production and catabolic rates. As trigs rise from low levels the scheme switches from non atherogenic to atherogenic LDL, with a plateau in the middle and higher values on both the lower and higher arms. At low trigs LDL… Read more »
George Henderson (@puddleg)
Guest
Hi Tim, I’ve been thinking along similar lines but hit a speed bump. On LCHF no TR-VLDL, less VLDL, more IDL and LDL released directly; this is also in Krauss studies. But IDL has less TG, LDL has next to none, so how are these lipoproteins contributing to increased fat oxidation? Where does this fit in the energy demand model? I see another aspect like this – when you don’t eat carbs you don’t need so much cholesterol. Synthesis has decreased, adipocytes are rejecting it, HDL has risen to collect it from cells, and it’s being transferred to IDL for… Read more »
Tim
Guest
Hi George. I think I agree but come at it from another angle. My take is that in healthy individuals at extremely low trigs LDL levels tend to be very low but production and catabolism very high so the hepatic LDLR activity is high. Here after a low carb/high fat meal LDLRs are available for catabolism of chylomicron remnants but tissue, adipose and muscle is fat replete and properly sized so the small amount of remnant fat gets recycled rapidly into IDL/LDL but catabolized very quickly so levels of LDL remain low but particles are large (with large lipid and… Read more »
JohnD
Guest
Dave, Some more data. First, I’m not 100% “LC”, Mornings are MCT and heavy cream coffee. Lunch Salad with some sort of protein (sardines, salmon, beef jerky…) Diet Coke, almonds and some 70% dark chocolate. Dinner is as LC as I can make it. (I eat with the family and don’t want to rock the boat). ice cream later at night Started in in Jan-2017 and dropped from 172 to 164 ish Run 4 miles 4 times a week (8:45 min miles) OR bike to work (30 to 45 miles total) 16->18 MPH average I consider myself reasonably athletic (compared… Read more »
Tim
Guest
Hi George/Dave. Further thoughts on the mobilization of cholesterol to/from plaque and fatty streaks and ectopic locations, this is a minor wrinkle on circulating LDL levels but may be important in some cases.. The major holder of cholesterol in plaque is macrophages that aggregate into foam cells. Cholesterol entering these structures is damaged or altered in some form, ie it is not the native cholesterol from pool a. The mechanism of entry is receptor mediated endocytosis, ie receptors are concentrated in coated pits and bind lipoproteins like damaged LDL by invaginating and passing the contained material to lysosomes to seperate… Read more »
Victoria
Guest

65 Y/O female LMHR here who already has plaque in LAD and exercise-induced angina. Reading this, and the papers you cite with great interest, been hacking the problem from every angle I can. Tim, please, you mentioned that HDL is the main acceptor candidate “although there are others” Can you point me to what they are?

George Henderson (@puddleg)
Guest

Hi Tim,

Sarah Hallberg’s experience is with weight loss and I’d expect the lowest rate of hyper-responders in that population based on the fasting studies (and my own impressions based on feedback for the What The Fat diet book).
I’m thinking if there was a large reduction in whole-body cholesterol as we’re discussing, this would take time because I don’t think fecal cholesterol reabsorption/excretion can be regulated by the LDL pool.
In low insulin states foam cells make cholesterol directly from glucose and don’t take in LDL, insulin switches this off. This is the opposite of liver, where insulin stimulates HMG-CoAR
http://journals.lww.com/cardiovascularpharm/Abstract/2008/10000/High_Glucose_Concentration_Increases_Macrophage.5.aspx

Andrea
Guest

Hi Dave,

Thanks for your passion in studying this topic!
I feel a bit puzzled because I almost fit your profile (lean,very active,with LDL going way up on low carb),however in my case hdl goes down and trigs up on low carb+intermittent fasting (never went full keto).Here are my values (all in mg/dl):

On low carb:
ldl 250
hdl 54
trigs 105

After 3 weeks of higher carb and lower fat:
ldl 141
hdl 60
trigs 41

I wonder if you have any insights into what might be the mechanism behind this pattern…

Thank you,
Andrea

Angela
Guest
Hi Dave, I conducted the Ketofest experiment at home in Florida (I’m saving my photo food logs for your Google Drive folder) and received my Friday morning lab results a few minutes ago (I fasted TWR except for supplements, coffee with HWC, water, salt). Here are some of the results: LDL-P: 2083 LDL-C: 185 HDL-C: 52 TG: 71 Total Cholesterol: 251 HDL-P: 24 Small LDL-P: 544 LDL Size: 21.5 C-Reactive Protein: 3.43 I’m a 52-year-old woman and I’ve lost about 30 pounds so far in 2017–currently 172–on a ketogenic diet with some fasting. I weight-train approximately four days/week (including last… Read more »
Daniel
Guest

Hi Dave,

We’ve talked before on the apoe4.info forum. Very interesting stuff here! Here’s my lab numbers as I progressed from a 50% carb diet to ketosis. I am 72 yrs, 10% body fat, moderately active, apoE: e3/e4. Although you can’t see it here because I keep my SFA down, thanks to my e4, I am a hyper responder to SFA.

http://imgur.com/XVWwzSG

Although I don’t take pictures, I’ve weighed and recorded my food intake for years as well as tracking other variables.

– Dan

Lewis
Guest

Any data on long lived people with healthy arteries & also have the LMHR profile?

pam
Guest

Another person with results for you. I’m a 48 yo female, keto diet for a 3 months–fairly active with swimming,
rowing, and yoga. Recent labs: Triglyceride 56, Total cholesterol 215,
LDL 132, HDL 72, Vldl 11, Chol/Hdl ratio 3

David Mitchell
Guest
I’m borderline. I started LCHF 5/4/15 on Mark Hyman beta program for EFGT book. I have stuck with it to date – perhaps 40-50 g carb / day on average including seasonal and other cheats. Here is something for your database. Note LDL values are Friedwald, but I believe better formula for would be Iranian formula for LCHF (see http://www.docsopinion.com/2017/01/02/ldl-cholesterol-overestimated-low-carb-high-fat-lchf-diet/ or use LDL (mg/dL) = TC/1.19 + TG/1.9 – HDL/1.1 – 38 (146 for my latest 6/17 physical with Friedwald 170, TC 255, HDL 72, TG 66; 6/16 was Fried LDL 141, 217, 63, 66). I’m not concerned about my… Read more »
Neville
Guest
Hey Dave, Few questions… – We hear that its not the cholesterol but the particle count where the risk is. However in all probability if your cholesterol is high, isn’t it likely LDL-p will be high too? Have you come across a major discordance between LDL-p and cholesterol numbers, like someone having cholesterol of > 350 but a LDL-p of 1500? – So i recently had a CIMT done [Right=0.87mm, Left=0.92mm] which definitely seems fine. In any-case, even the technician agreed that calcium score trumps CIMT when it comes to heart disease risk. My calcium score did increase on a… Read more »
Craig
Admin
Neville, LDL-C and LDL-P sometimes are sometimes discordant, meaning one is high when the other is low. If you account for LDL-P, LDL-C has almost no value as a risk factor. Here’s a good article on the topic: http://eatingacademy.com/nutrition/the-straight-dope-on-cholesterol-part-vi I expect both nature and nurture factors would contribute to a calcium score in middle age. However, I would think that there are traditional lifestyles where most elderly individuals have 0 scores (just based on very low incidence of CVD in almost all pre-agricultural societies). Steady accumulation of plaque seems to be a modern affliction. Relating to diet changes, if you… Read more »
Neville
Guest

Thanks Craig

Csilla
Guest
Hi Dave, Thanks for your blog. I’m 39 years old woman, 49-50 kg, 162 cm. I go to gym 2-3 a week and I do yoga. I’m on keto since 2 years and I eat 8/16 or 6/18. 18-20% fat mass. Before ketogenic diet my results are: TC: 7,1 mmol/l (273 mg/dl) TG: 0,79 mmol/l HDL: 2,48 mmol/l LDL: 4,24 mmol/l Glucose: 5,1 mmol/l H1A1c: 5,5% TSH: 2,65 uIU/ml …and with keto: TC: 17-20 mmol/l (660-769 mg/dl) TG: 0,89 mmol/l HDL: 3,82 mmol/l LDL: 15,78 mmol/l Glucose: 3,8-4,4 mmol/l H1A1c: 4,8-5,0% TSH: 1,8 uIU/ml Apolipoprotein A1: 269,0 mg/dl (ref: 125,0-215,0)… Read more »
George Henderson (@puddleg)
Guest
Hi Dave and Tim, I found this paper on high cholesterol in the diabetic (near zero insulin) rabbit. it says When cholesterol influx into arteries is reduced, in spite of high plasma chol levels, atherogenesis is prevented. http://www.jlr.org/content/29/11/1491.full.pdf They’ve used alloxan to drastically reduce beta cell function. The lack of insulin plus the high dietary cholesterol load results in large particles, and these aren’t being taken up. Now, these lipoproteins are full of TGs, and the rabbit has no CETP, so there are differences from our human models. But, in principle, LDL and other particles can be rejected by arteries… Read more »
Justin
Guest
Hi George Here are two more articles on diabetic rabbits with hypercholesterolemia: https://www.ncbi.nlm.nih.gov/pubmed/18129862 https://www.ncbi.nlm.nih.gov/pubmed/13130788# And here is a one with a diabetic dog where insulin administration caused atherosclerosis: http://circres.ahajournals.org/content/9/1/39.long In response to your earlier question “so what if foam cells STOPPED consuming LDL in low inflammatory states? Would that make LDL pile up in serum?” – Here are two in vitro studies on the effect of insulin on the monocyte LDL receptor https://www.ncbi.nlm.nih.gov/pubmed/2843407 https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3407326/ The LDL receptor seems “linked” with the insulin receptor as both a properly functioning insulin receptor as well as a small amount of insulin are needed… Read more »
George Henderson (@puddleg)
Guest
” A suppression of LDL-receptor activity resulting from deficiency of insulin and elevated plasma catecholamine concentrations in uncontrolled insulin-dependent diabetic patients may contribute to the increased levels of LDL cholesterol observed in these patients.” All good stuff and I think there is a shut-down of LDL-R simply due to less cholesterol being needed by all sorts of cells in the pseudo-unfed state, combined with a dumping of the excess cholesterol from shrinking cells like adipocytes and possibly reversing plaques. Looking at epidemiology, merely to create a narrative around this, I’ve found populations – Malmo is the best example – where… Read more »
Justin
Guest

Those are good narratives. I particularly like the Denmark paper, although I wish they had stratified by statin usage instead of adjusting for it. I think aging to 50+ without developing diabetes or CVD likely means the participants are relatively normo-insulinemic, which explains the following: “However, we did exclude all those with a diagnosis of CVD or diabetes at baseline. These subjects could be the vulnerable subjects, leaving a population resistant to the harmful effects of high LDL-C or TC levels.”

George Henderson (@puddleg)
Guest

The Demark paper is consistent with healthy high LDL being a side-effect of HDL efficiency in a high-fat population, while unhealthy high LDL (or any LDL) will associate with poor HDL function.
Many people are diagnosed with CVD or T2DM over the age of 50, probably most are, there’s a bit of discussion around this in the paper. And the lowest LDL category, <2.5 mmol/L, includes the healthy recommendation – it's not some freakishly low "occult disease" group.
As the statin use was voluntary not randomised it's hard to say what effect it had.

Eran
Guest
Hi Dave. This caught me at perfect timing! I was just sent by my doctor to a lipidologist because my LDL is too high. I am not LCHF, but a strict Paleo for years, and beacuse I’m very lean and active I live on around 150-200 gr of carbs daily, usually much more. My LDL and HDL rose significantly on this diet, while my trigs are very low. Can your protocol work on this type of diet? If so, can I up my calories intake by upping only the fat? What type of fat do you recommend (I understand not… Read more »
Craig
Admin
Eran, So far, we have had mostly LCHF’s do the protocol, so I’d be awesome to get some more data on other types of diets. At 150-200g of carbs, you might be closer to the carb-swap experiment that Dave did. Exercise also has an impact. The interaction between gut-based and liver-based delivery of fat energy is the most likely driver of the inversion pattern. All other things being equal, eating more fat in the 3-days prior to a test should drive down LDL. In the ketofest experiment, there was no guidance on type of fat, just proportions of macros. I… Read more »
Anna
Guest
Hi Dave, so I’m basically a 29-year-old female I weigh 150 lbs , and I’m 5’6 y’all. I started the keto genic diet about 3 1/2 weeks ago, and I felt 100% better on it and I’ve even lost 8 pounds . I went in for some bloodwork, and when my total cholesterol came back it came back at 393!! My doctor wanted to put me on a Statin. And do another blood test in a month.i’m afraid that I might be a hyper responder, and I’m afraid that I won’t be able to continue at this rate I don’t… Read more »
Craig
Admin
Anna, If you feel great and look great on keto, that’s 2 very strong reasons to KCKO (keep calm, keto on). If you are also happy with your lifting and HIIT performance, you’d need to hear a very strong argument to change back to your old diet. (although 3 1/2 weeks is barely enough time to become athletically fat-adapted) I’m not convinced high LDL-C alone is enough evidence for any change, either to add back the carbs or start taking a Statin. If you just want to lower LDL-C for your doctor, follow Dave’s protocol for 3 days before your… Read more »
Anna
Guest
Hi Dave, so I’m basically a 29-year-old female I weigh 150 lbs , and I’m 5’6 y’all. I started the keto genic diet about 3 1/2 weeks ago, and I felt 100% better on it and I’ve even lost 8 pounds . I went in for some bloodwork, and when my total cholesterol came back it came back at 393!! My doctor wanted to put me on a Statin. And do another blood test in a month.i’m afraid that I might be a hyper responder, and I’m afraid that I won’t be able to continue at this rate I don’t… Read more »
Kevin Fansler
Guest
I am a hyper-responder who is now 79 years old. My total cholesterol was around 200 with a healthy conventional diet 15 years ago. My triglycerides were nearing 400. My testosterone level was 289 ng/dL and I started taking testosterone supplements. My doctor later prescribed Lopid to lower the triglycerides. I decided to go on an LCHF diet instead. This approach brought my TG down near 100, but my TC went up to around 350. I was on this regime for around 12 years when I decided to go off my testosterone supplement. The resulting testosterone level was a perfectly… Read more »
Kevin Fansler
Guest
I am a hyper-responder who is now 79 years old. My total cholesterol was around 200 with a healthy conventional diet 15 years ago. My triglycerides were nearing 400. My testosterone level was 289 ng/dL and I started taking testosterone supplements. My doctor later prescribed Lopid to lower the triglycerides. I decided to go on an LCHF diet instead. This approach brought my TG down near 100, but my TC went up to around 350. I was on this regime for around 12 years when I decided to go off my testosterone supplement. The resulting testosterone level was a perfectly… Read more »
Craig
Admin

Great story, Kevin. Sounds like you took control of your own health and got to a great place that wouldn’t have been possibly blindly following the advise you were given.

Vijay Iyer
Guest

My report after 3 month of keto

BLOOD KETONE (D3HB) – 5.5 mg/dL

Cholesterol Test

TOTAL CHOLESTEROL > 500 mg/dl

HDL CHOLESTEROL – 85 mg/dl

LDL CHOLESTEROL – > 300 mg/dl

TRIGLYCERIDES – 100 mg/dl

TC/ HDL CHOLESTEROL RATIO – 5.9

LDL / HDL RATIO – 3.5

VLDL CHOLESTEROL – 20 mg/dl

NON-HDL CHOLESTEROL – 414.8 mg/dl

Diabetes Test

Fasting INSULIN – 2.12

HbA1c – 5.4

FASTING BLOOD sugar – 92

Craig
Admin

Thanks for sharing, Vijay. Did you happen to have your pre-keto numbers to compare against? I assume you are feeling great, otherwise you’d have switched back.

Mike
Guest

I don’t quite fit.
Here is my Nov. 14 2016 lab report:

LDL-P 2943
LDL-C 305
HDL-C 61
TG 76
TC 381
HDL-P 29.0
Small LDL-P 692
LDL Size 21.8

An April 12, 2016 DEXA body scan had me at 17.8% fat.

That seems not very lean yet for my age at the time of 60.4 years that put me in the 1st percentile. I.e., 99% of people my age had higher total body fat percentages.

George Henderson (@puddleg)
Guest

Hi Mike,

I’m probably not super-lean either but I think leanness might be a genetic category here, with most people in it being lean, and same with activity, being a born fidget at any lean mass might be similar to being an athlete.
Or another way of looking at this, the level of fat mass at which your metabolism decides you’re lean enough can vary.

Mike
Guest
Sorry for the second post but I just found an Oct. 24 2015 NMR. Feel free to combine this with my previous post. LDL-P 1831 LDL-C 232 HDL-C 72 TG 70 TC 317 HDL-P 33.4 Small LDL-P 213 LDL Size 21.9 From Cronometer, here are my macros for the five days preceding the blood draw: 11/9/16-11/13/16 2415 kcal; 100 g PRO; 22 g CHO; 218 g fat 10/19/15-10/23/15 3440 kcal; 96 g PRO; 24 g CHO; 335 g fat Basically an increase of 50% in fat brought LDL-P down more than 1,000 nmol/L, LDL down more than 70 mg/dl, and… Read more »
Craig
Admin

Mike, thanks for sharing your data! Another solid example of the Inversion Pattern in action.

You’re reminding me I should go eat some more to improve my numbers for tomorrow. It’ll be my first NMR Lipoprofile.

George Henderson (@puddleg)
Guest
Assuming that CETP is accelerated in the LMHR phenotype, Transfer of CE from HDL directly to LDL by CETP could also be antiatherogenic if the LDL is cleared by the liver LDL receptor. This role of RCT is especially important if the original source of cholesterol is from plaque (4). As this process is potentially antiatherogenic, inhibition could be disadvantageous. An additional concern is that excessive CETP inhibition increases HDL-C to supra physiological levels (>70 mg/dl), which appear to result in paradoxically high rates of cardiovascular disease (CVD), as shown in several epidemiological studies (13, 14) and in one CETP… Read more »
David
Guest
Hi, Dave. I’ve been reading through with interest. I’m T2 on LCHF with normal weight, normal BG but high lipids. I will post my numbers when I can dig them out, but I’m intrigued by your theory that lean athletic people eating low carb tend to run higher blood fat levels. A simple take on this could be that the body is learning that it is more efficient to store fat in the blood than in fat cells because the fat is always being burned off at a high rate. I would be interested in the mechanism the body uses… Read more »
George Henderson (@puddleg)
Guest
Here’s an idea; keto is a pseudofasting state. Fasting elevates LDL. So, does already being in a pseudofasting state predispose us to a more rapid effect of fasting itself, so that the short fast before a lipid test is enough to push up lipids? That is, does a lean, healthy, active ketogenic dieter experience a rapid transition to fasting state lipids? This would be consistent with your hypercaloric feeding experiments – the extra energy and insulin response to that slows the transition to the fasting state afterwards. Does anyone have non-fasting results? And wouldn’t these be bollixed anyway because chylomicrons… Read more »
Craig
Admin
Funny enough, I actually got a blood lipid test in a non-fasted state by accident. I thought they would defer my test to the next day because of that, but they just said “they’ll adjust for it” (ha!). Test1 is 2 hours after a hearty bacon & eggs breakfast, but 36 hour fast before that breakfast. 2-months later, test2 is 3-day low-calorie, test3 is 3-day high-calorie. TC 342 360 367 333 TRIG 176 80 68 51 HDL 98 113 115 114 LDL 209 232 238 209 Just a few data points, but take it for what you will. UPDATE: Added… Read more »
George Henderson (@puddleg)
Guest

This paper finds that even in the normal diet non-fasting lipid test has lower LDL and higher TGs, same HDL.
https://www.ncbi.nlm.nih.gov/pubmed/18955664

So it’s not a stretch that a pseudofasting diet can push this relationship further in the opposite direction

George Henderson (@puddleg)
Guest

So not as much difference between low and high calorie, as between fasting and non-fasting.
And non-fasting really skews the TG/HDL ratio – but does lower LDL and total C. So the chylomicrons in your case seem to be in the TG fraction, and it’s likely that a better separation that removed chylomicron cholesterol from the equation would see LDL even lower.
As far as we can tell from 3 tests anyway!

Craig
Admin

Now 4. 🙂 I think my body was eating up those LDL-C’s to rebuild my sore muscles.

George Henderson (@puddleg)
Guest

FYI, here’s an animation of the cholesterol transport system that has most of the working parts, including the role of the various lipase enzymes

George Henderson (@puddleg)
Guest
To support my “Reverse Cholesterol Transport on Steroids” model, this paper studying the kinetics of hypercholesterol feeding in the guinea pig model. Guinea pig is a good human-equivalent lipoprotein model, and Fernandez works with Jeff Volek now. Guinea pigs were fed 15% (w/w) .fat diets (lard, olive oil, or corn oil) with cholesterol levels corresponding to absorbed intakes of 6 (basal), 50, 100, or 200% endogenous cholesterol synthesis. Guinea pigs maintained stable plasma cholesterol levels until cholesterol intake equaled or exceeded endogenous synthesis (P corn oil, with olive oil being intermediate (P < 0.05). Hepatic membrane apoB/E receptor number (Bmu)… Read more »
Joseph
Guest

Hi Dave,
Could you please give me your E-mail address for sending you my CIMT and Calcium Scan test reports? I have done them as you had suggested.
Thanks.