Note from Dave: This long-awaited installment from Siobhan is a must-read for every female interested in cholesterol and risk. Enjoy! |
The First Hint
As the #LDLBounty continues, and the question of whether high LDL in isolation raises the risk of cardiovascular mortality (or all-cause mortality) in and of itself remains unanswered, there may be a group which may give one even more pause when contemplating the answer. My first hint that things weren’t exactly equal in regards to cholesterol between men and women was way back in 2015. Far before I had even thought about picking up a textbook on lipidology, I noticed there seemed to be something a little odd going on in regards to women and high cholesterol levels. For one, I had heard talk of some research that women with low cholesterol were more at risk for symptoms of depression1, 2, and while I found this interesting it was merely an association. So what if you’re less likely to become depressed if you have higher cholesterol as a woman? You’ll still be more likely to die of things like heart disease, and die more over all, anyway.
Right?
More Cholesterol, Less Death
In fact, there appears to be a bit of a difference when it comes to women and men in regards to mortality risk when it

From: doi:10.1111/j.1365-2753.2011.01767.x
comes to cholesterol. Because, while in men it appears as though there’s a U shaped risk when it comes to
cholesterol levels – meaning that rates of death are higher with lower and higher total cholesterol – with women it appears to be quite a bit more simple. As stated in the paper3, in women it appears as though when cholesterol levels are higher, death from all causes is lower.
That study didn’t appear to be a random fluke, either. As time went on I found more4, and more5 and more6 studies all showing that, specifically in women, either there was no difference in death from all causes with varying cholesterol levels, or those in the lowest cholesterol group had the highest rates of mortality. But, admittedly, this is looking at total cholesterol, so I thought that at the very least higher LDL (often considered the true bad guy in regards to cholesterol) would correlate to higher mortality rates.
More of the Same
Even after looking for studies which looked at LDL levels in regards to the rate of mortality and cardiovascular disease, the result ended up being the same with studies I encountered generally coming to similar conclusions. Some said that LDL levels in women were “not significantly related” to all-cause mortality7, while other said that LDL was not associated with Peripheral Artery Disease in women8, and yet more indicating variations of the same result.9, 10
But, clearly women aren’t bulletproof when it comes to cardiovascular disease, as they get it at about the same rates as men do, and it’s not like we’re especially good at avoiding death in general (as much as we might like to think of ourselves as invincible), either. So, it doesn’t appear as though this is a case of women being immune to cardiovascular disease, or being particularly resistant to death, so much as total cholesterol and LDL seemingly being poor predictive markers for women.
Now What?
If neither LDL nor total cholesterol is especially predictive in women, then what can we look for to determine our risk? Some studies indicate other, potentially more relevant markers for women, and luckily no additional tests need be ordered, as the information can be found on a standard lipid panel.
For example several studies found that the ratio of triglycerides to HDL were predictive of carotid plaque11, insulin resistance12, 13 (which is related to increased cardiovascular disease risk), cardiovascular mortality14 and all-cause mortality in women.15 Atherogenic Index of Plasma (AIP) also has some promise to better predict all-cause mortality among women.16 Although AIP is unlikely to show up on your lab report, you can easily calculate it via our report tool so long as you have your triglyceride and HDL levels.
While these markers do appear to predict cardiovascular and all-cause mortality risk better than Total Cholesterol or LDL this doesn’t mean that these markers are perfect. For one, both of these measures can be impacted by how long you fasted before the test, as well as issues which may raise triglycerides in isolation. Use of medication which influences HDL and triglycerides may also potentially interfere with their value as health markers, as well, so looking at multiple risk markers together may help avoid some of the pitfalls of relying on one marker alone.
Final Note From Siobhan
As always, the evaluation of personal health is a topic that, first and foremost, should be had with your doctor. Likewise, we always recommend researching all reputable sides of this debate as we do ourselves.
Sources
1 Horsten, Myriam, et al. “Depressive Symptoms, Social Support, and Lipid Profile in Healthy Middle-Aged Women:” Psychosomatic Medicine, vol. 59, no. 5, 1997, pp. 521–28. Crossref, doi:10.1097/00006842-199709000-00009.
Thanks for doing this important work! I have high LDL cholesterol in isolation but had a CT Scan that showed I have absolutely no evidence of coronary artery disease! I am 53 and have been doing LCHF since November 2016. I believe I am going to live a good long time!!
Glad to hear of your 0 CAC! Of course, regardless of who it is I really prefer not to look at LDL in isolation. It just appears to be especially unhelpful of a thing to look at in women, especially if comparing against HDL and TG levels… 🙂
There should be results for the upper and lower levels of Cholesterol and a careful and accurate examination to consider the possible risk for fat and cholesterol levels.
https://www.baneh.com
thanks
In your review of the literature, did you find that HDL became “good” because people were trying to determine why women’s heart disease rates were lower than men’s and came up with this idea? (This has always been my understanding, but could be — and likely am — wrong.)
Also, is there one reference study we could use (say, a meta-analysis or review) to illustrate this concept? I always say that higher TC (or even LDL) appears to be protective for women, but then I don’t have anything to back that up, other than all the people whose views I trust and who have researched this say this is the case.
And this points out yet another reason our older-male-dominated medicine fails: researchers (men) think that what applies to older men should apply to everyone else, women, children, etc., and that may or may not (in many cases, is not) true.
Hi Bob –
I think HDL was simplified down to “good” because they noticed in people in general higher HDL generally related to longer life, and fewer heart attacks (barring some exceptions like alcoholics).
It’s not just in women that high HDL (paired with low trigs) is a good marker, there’s some additional evidence it can be applied to the general population as well.
I don’t particularly like using one study or meta analysis to claim anything, so when I went in to see my doctor I brought in a few of the studies cited here. If you go to the bottom of the article and click on “sources” I list which studies I’m referring to – you may find those helpful.
Sorry to but in with a different topic but did you post your final results from the beef vs pork tests anywhere or Did the video CCW4 cover it? Thank you sorry again for interrupting
Hi Adam,
No worries – all the up-to-date results were shown in CCW4, but I’m waiting to do a write up once I try two more experiments (pork vs pork + l-carnitine, and pork vs fish [with added fat]). This should help me isolate what exactly caused the drop.
Awesome looking forward to it
Hey Dave do you have any idea of a solely fish diet over 1-2 weeks would drastically impact cholesterol? My LDL has tested anywhere between 350 (after 2 weeks of fasting) and 220 (fasted 12 hours), I’m tempted to test it out for a week or two.
The idea was:
Normal Diet for 1 week, fast 12 hours, get blood results
Only fish/light calories/fasting for 2 weeks, fast 12 hours, get blood results
fast 1 more week, get blood results
مطلب بسیار باحالی بود و ممنوم از شما
Thank you for the AIP report tool. I put in my numbers and got an answer of
AIP: -0.252 >>> Lowest Risk Third Is that a truly a negative number? That seems too good to be true!
Yes, AIP starts at .11 as “Average” and goes up or down from there (higher means more risk, lower means less) including into the negatives.
It’s not too good to be true, you really did score that low 🙂
Siobhan, I am assuming these are all good? Can you confirm. I am not really familiar with AIP especially. Thank you for all you do here and on the KKAB page.
Hi – if you’re talking about the two alternatives used (AIP and TG:HDL), yes according to what I’ve read they seem to work pretty well.
Instead of TG:HDL ratio I generally go with “HDL >50, and trigs <120" to allow normal fluctuation of the markers, though.
And of course I try not to determine health from one marker alone - I try to look at multiple all together to see if I can get a better look at the big picture.
I’m preparing for my first blood testing after 6 months Keto and Carnivore for the last 4 months. I will be going to Quest Diagnostics and will be self-paying, so I want to get the most bang for my bucks 🙂 A semi-retired Naturopath has offered to call in my prescription, but is unsure what to request considering my WOE and cholesterol concerns. I have had kidney stones n the past (last bout 2 years ago) so I also want these levels checked. I was overwhelmed at the number of test available on the Quest website and wonder if you can help me out? I will be posting my results as soon as I receive them. Thanks for all your great work!
Kelle
I’m not sure about kidney stones, but we have a list of possible lab tests you could get to check overall/metabolic health. Perhaps that would be a place to start?
At the very least I try to get a lipid panel, NMR lipoprofile, hs-CRP, and fasting insulin, if that helps.
What are good studies to give your doctor when they want you to start on statins?
If you want some examples of studies that might work as good conversation starters, I can provide examples of the ones I brought, I just printed the abstracts and highlighted pertinent info:
https://www.ncbi.nlm.nih.gov/pubmed/21951982
https://www.ncbi.nlm.nih.gov/pubmed/11253736
I also printed out the two tables from this post.
Obviously these are just examples, I highly suggest reading through some of the citations on this article, this list, and of course research outside of our site as well 🙂
Of course – it’s worth noting that while I think it definitely is beneficial to back up your reasoning for why you do or don’t want to do something your doctor suggests, it can help to remember that your doctor cannot make you do anything you don’t want to do. It is ultimately your choice on whether you take any medication or treatment that’s recommended.
Hopefully these examples help you get started and you have a fruitful conversation, though.
Most of the studies and discussion I see about cholesterol and disease is all about impact on coronary disease. What about stroke risk? and Small Vessel Disease (SVD) in the brain? can we translate effects of diet and cholesterol on the heart and it’s vascular system to the brain and it’s blood vessels?
Definitely agreed a lot tend to focus exclusively on heart disease. There are other studies regarding stroke risk, but the studies interested me most generally related to all-cause mortality (Death from all causes). This helps avoid the conundrum of “Sure, I die less of heart disease, but what about…” by instead looking at just dying early in general, regardless of whether from stroke, heart disease, cancer, and so on.
Siobhan, thanks for the great article! Just got my labs back. Been LCHF for a year or greater, not sure. Labs seemed good but WBC and RBC were low-ish, 3.9 and 4.11 respectively. Not sure if that’s a dehydration thing or not. What I find interesting was my A1c (5.1) and Trig (56) were good, my glucose was 118. Wondering if you had thoughts on this.
Thanks! Keep on Keeping on!! 🙂
Michele
-==== CholesterolCode.com/Report v0.9.3 ====–
…012 months on LCHF (20g to 120g carbs) ::: 18 hours water fasted…
Total Cholesterol: 236 mg/dL 6.1 mmol/L
LDL Cholesterol: 118 mg/dL 3.05 mmol/L
HDL Cholesterol: 100 mg/dL 2.59 mmol/L
Triglycerides: 56 mg/dL 0.63 mmol/L
–CHOLESTEROL REMNANTS–
Remnant Cholesterol: 18 mg/dL 0.47 mmol/L >>> Medium-Low Risk Quintile
Remnant Chol to HDL: 0.18 >>> Lowest Risk Quintile
Go to https://tinyurl.com/y84u92wm for more on Cholesterol Remnants
–ATHEROGENIC INDEX OF PLASMA (AIP)–
AIP: -0.614 >>> Lowest Risk Third
Go to https://tinyurl.com/ycccmmnx for more on Atherogenic Index of Plasma
–CONVENTIONAL MARKERS AND RATIOS–
Friedewald LDL-C: 125 | Iranian LDL-C: 99
Total/HDL Ratio: 2.36
TG/HDL Ratio in mg/dL: 0.56 | in mmol/L: 0.24
Hi! You’re welcome 🙂
Your LDL is a bit low from what I’d expect of that profile. Do you do any exercise, like endurance running or resistance training for example? Sometimes it seems there can be a higher fasting glucose than would be expected in a low carber. This *may* be a consequence of adaptive glucose sparing (preserving glucose for tissues that need it), especially in people who are athletic. The tell is these people tend to have low fasting insulin (generally <5). Do you know what yours is?
Thanks for the quick response. I did go for a 3 mile run the morning of the blood draw. I do try to workout regularly but as of lately, there hasn’t been a lot of resistance work. I have not had my fasting insulin done. Unfortunately not on this work up – need to find somewhere to get it ordered. Would dehydration after a workout play into it?
on diet:
12
total hours WATER fasted before the test.
(In other words, total time between your
last meal or coffee/beverage and the blood draw for this test.)
Units of measurement:
327
Total Cholesterol (TC)
196
LDL Cholesterol (LDL-C)
110
HDL Cholesterol (HDL-C)
43
Triglycerides (TG)
(Copy and paste everything below for reuse)
–==== CholesterolCode.com/Report v0.9.3 ====–
…5 months on Keto (less than 20g carbs) ::: 12 hours water fasted…
Total Cholesterol: 327 mg/dL 8.46 mmol/L
LDL Cholesterol: 196 mg/dL 5.07 mmol/L
HDL Cholesterol: 110 mg/dL 2.84 mmol/L
Triglycerides: 43 mg/dL 0.49 mmol/L
–CHOLESTEROL REMNANTS–
Remnant Cholesterol: 21 mg/dL 0.54 mmol/L >>> Medium-Low Risk Quintile
Remnant Chol to HDL: 0.19 >>> Lowest Risk Quintile
Go to https://tinyurl.com/y84u92wm for more on Cholesterol Remnants
–ATHEROGENIC INDEX OF PLASMA (AIP)–
AIP: -0.763 >>> Lowest Risk Third
Go to https://tinyurl.com/ycccmmnx for more on Atherogenic Index of Plasma
–CONVENTIONAL MARKERS AND RATIOS–
Friedewald LDL-C: 208 | Iranian LDL-C: 159
Total/HDL Ratio: 2.97
TG/HDL Ratio in mg/dL: 0.39 | in mmol/L: 0.17
in your protocol no vegetables al all? Just meat and cheese for three days?
-==== CholesterolCode.com/Report v0.9.3 ====–
…5 months on Keto (less than 20g carbs) ::: 12 hours water fasted…
Total Cholesterol: 327 mg/dL 8.46 mmol/L
LDL Cholesterol: 196 mg/dL 5.07 mmol/L
HDL Cholesterol: 110 mg/dL 2.84 mmol/L
Triglycerides: 40 mg/dL 0.45 mmol/L
–CHOLESTEROL REMNANTS–
Remnant Cholesterol: 21 mg/dL 0.54 mmol/L >>> Medium-Low Risk Quintile
Remnant Chol to HDL: 0.19 >>> Lowest Risk Quintile
Go to https://tinyurl.com/y84u92wm for more on Cholesterol Remnants
–ATHEROGENIC INDEX OF PLASMA (AIP)–
AIP: -0.8 >>> Lowest Risk Third
Go to https://tinyurl.com/ycccmmnx for more on Atherogenic Index of Plasma
–CONVENTIONAL MARKERS AND RATIOS–
Friedewald LDL-C: 209 | Iranian LDL-C: 158
Total/HDL Ratio: 2.97
TG/HDL Ratio in mg/dL: 0.36 | in mmol/L: 0.16
Are there any risk for me?
Mine was, yes, but it can be altered to suit your preference, of course. 🙂
The important part – if you’re wanting to do the cholesterol lowering portion of the protocol – is high fat very low carb high calorie for 3 days. It’s best to pick foods you know you can eat a lot of.
By the way – by these numbers it looks like you’re a lean mass hyper-responder!
–===== CholesterolCode.com/Report v0.9.5.15 =====–
• Female • 48 • Coffee: 0 cups/day •
• 5 on months on LCHF (20g to 120g carbs) •
• 17h water fasted • Cholesterol Rx: false •
Total Cholesterol: 303 mg/dL 7.84 mmol/L
LDL Cholesterol: 183 mg/dL 4.73mmol/L
HDL Cholesterol: 113 mg/dL 2.92mmol/L
TG Cholesterol: 35 mg/dL 0.4mmol/L
———RISK REPORT———
Atherogenic Index of Plasma: -0.863 mg/dL >>> Lowest Risk Third
—-> Go to https://tinyurl.com/ycccmmnx for more on AIP
Framingham Offspring: 0.7 Odds Ratio >>> Low Risk
—-> Go to https://tinyurl.com/y5fc5adl for more on this Framingham study
Jeppesen: >>> Lowest Risk Third
—-> Go to https://tinyurl.com/y63xp7lj for more on the Jeppesen study
Cholesterol Remnants: 7 mg/dL >>> 0.08 mmol/L >>> Low Risk
—-> Go to https://tinyurl.com/y84u92wm for more on Cholesterol Remnants
——CONVENTIONAL MARKERS AND RATIOS——
Friedewald LDL-C: 183 | Iranian LDL-C: 132
TC/HDL Ratio in mg/dL: 2.68
TG/HDL Ratio in mg/dL: 0.31 | TG/HDL Ratio i
This report is from November..and after I’ve been grain free for about 5 months ( I have celiac disease but I seem to react to all grains, esp hidden corn). I was mainly living on lots of eggs at the time as that was the only thing I could tolerate. Since then I found I can eat lamb from New Zealand. Other meats seem to cause issues. I eat very clean and it’s not unusual for me to walk for 3 or 4 hours at a time. I’ll do that several times a week. I also carry all of my groceries home from a few stores, carrying then miles. I can carry 20 pounds for about 2 miles without any problems..I prefer to do all.of my walking on an empty stomach, so only drinking water.
I’m feeling better and I’ve noticed other improvements too. Like some wrinkles I had on my forehead seem to be almost gone. And any injury seems to heal really fast?!
The longest I’ve ever fasted was about 25 hours. Because I’m worried about getting all of my nutrition. I need my body to heal from 20 years of undiagnosed celiac which has taken a big toll.
The advice from my doctor was to eat “healthy whole grains” everyday when I have celiac disease! Which is crazy. I even react to airborne particles from places that are cooking grain, like if I walk past a bakery or a fast food. I started OMAD and keto hoping some of these reactions might go away..the airborne ones I mean. I started keto in January.
The hemoglobin A1C says
Ref range & units: 4.0 – 5.6 percent. 5.0
I guess my number is 5.0???
Oh the other advice the paper gave to “lower cholesterol” is to “start walking” and that I should stop eating eggs, cheese and red meat. Well due to reactions to most normal food I won’t be able to eat anything!! I’d be stuck living on lettuce! How can I walk to where I need to go if I’m living on lettuce? I also can’t get the nutrition from that. You can’t get B vitamin or iron from lettuce! Oh I walk 3.5 or 4 miles per hour. I also do body weight training. And I lift small weights.
I don’t seem to catch cold or flu even if people cough on me.
The Dr did want to prescribe some junk but I’m not taking anything. I can’t even take over the counter stuff, like a cough drop, as I react to it. So I don’t trust anything.
Hi, this looks pretty close to the Lean Mass Hyper-responder profile. E.g. someone who is lean and/or active and powered by fat (e.g. on a high fat low carb diet). I can’t give any medical advice, as I’m not a doctor, but personally my own rule for fasting is if I get the urge to and can do so easily, I will, if not I assume it’s for a reason and eat as I get hungry. But I try to keep things as simple as possible for myself. 🙂
I suppose as far as your doctor suggesting grains, it’s fair to say that some grains are technically gluten free like rice or oats – but on the other hand it’s helpful to remember that it’s your doctor’s job to give you advice that can improve your health, but ultimately it’s up to you to decide if that advice helps you reach your goals or not.
In order to do that it can help to look at the best arguments from different perspectives so you can decide on what seems most plausible to you. For example, there’s a presentation from Dave approaching from a cautiously optimistic perspective on high LDL in the context of low carb, and there’s also this post from Dr. Nadolsky showcasing a cautiously pessimistic perspective.
I have a high calcium risk score. My LDL did get much higher during menopause. Statins have kept it down. My cardiologist raised my statins because of my calcium risk score. I am on a modified Keto diet and have lost 14 pounds so far. I am 155 lbs. I am told there is nothing I can do about calcium risk score. Your thoughts? I have inflammatory arthritis, which, oddly, gets better in England (?) and flares up here in Az. My fingers have fused due to it. I have replaced my knees. I am on Deborah Murtagh program and I am no longer taking anti inflammatories but the burning in my hands and neck grinding get worse .