Unkind labs with keto diet - where to go from here?

[DanH44]

Hi all,

I was hoping to get some input from the many keto experts we have. Back in early 2106, I read in the forum here about the apoe4 metabolic shortfall and decided to try keto. Starting from dietary 50% carbs, I began gradually reducing my carb and protein intake, getting labs every 2-4 months. Here's the lab data below - I also uploaded it to the group biomarker archive:


(image will get bigger if you RM-click it and open it in a new tab)

I was very happy with how it went until I saw the last lab result in the list - Jul 12. Problems are:

• LDL-P way higher than I'm comfortable with
• TGs are higher than I've ever seen since I stopped eating junk food
• My HDL-C took a hit
• My IR score topped 25 for the 1st time ever
• My VLDLs are getting bigger

What we are seeing here is classic insulin resistance, starting to evidence at my May labs and worse now in July. Peter at Hyperlipid would say, oh that's physiological insulin resistance; nothing to worry about. But, is it really benign or am I in disease territory? Have any of you seen bad numbers like these?

The LDL-P really took a turn to the dark side. Here's what it looks like against LDL-C:



LDL-C (yellow) tracks my SFA intake very strongly with a correlation of 0.885. But, clearly something extra is affecting LDL-P (blue) with the correlation of only 0.594 and the 3 outliers I circled in red. But, notice the high-low pattern of individual labs is preserved between LDL-C and LDL-P - except for the last one that reflects the insulin resistance - as does the bloated VLDL and other numbers for that date.


The strange part about it is, I didn't change much between early May and July. I wanted to try reducing my hazelnut intake (to lower omega-6). This dropped my calorie intake so I lost a little weight and although my absolute SFA dropped, its %en rose. And I lost the fiber in the nuts. And, finally, I switched my fish oil supplement from Now Ultra omega-3 to the lef Super Omega-3 because it had more DHA and I added a gamma-tocopherol supp in mixed tocopherols also from lef.com

Well, I guess the obvious thing to try is to role back those changes and retest. But I really want to hear from anyone who has any ideas about this.

Thank you in advance for any help.

[Noogie]

It's great that you're keeping such detailed records.

Is there any chance there could be another factor that is being overlooked? Is there any other bloodwork or other labs that you get done on a regular basis? I only mention this because I had a doctor briefly mention I might be insulin resistant when I was having blood sugar issues that coincided with huge hormonal swings that I hadn't experienced before (Total estrogen- not individual estrogens, those were in "normal" ranges- and I was not on any hormonal therapies). Have you been feeling any different? Headaches, racing heart, tiredness? I also had one test result with elevated testosterone but that didn't seem to impact my glucose levels. I also stay away from soy because I recognized that when I consumed any, I could get similar symptoms as I did when I knew for sure my hormones were through the roof and were messing with my blood sugar levels.

Also, are you consuming large amounts of olive oil (like in a Mediterranean diet) or anything like turmeric or grape seed extract? I don't know if any of those could affect lab results the way yours are, but just wanted to check. Do you by any chance check your blood sugar levels yourself before and after meals (the same way a diabetic has to)?

Not sure if this helps much, but please come back and post your next results after you make some changes and maybe there will be some enlightening info there.

[Julie G]

Nice to see you posting, Dan. you know I'm not a physician, nor exert of any kind, but I've been following a similar approach for several years and am happy to share a few thoughts. First, congrats on such great record keeping and careful vigilance of biomarkers. You are a role model for us all. My first thought was- a suboptimal thyroid. Then, I saw your TSH . My guess is that you're using medication to upregulate? Good for you.

After ruling that out, I noticed that your SFA intake has slowly risen while your fiber intake has concurrently dropped. It could be that simple. I get around 50 grams of fiber a day from a combo of my vegs and SunFiber, a prebiotic guar gum, recommended by my FMP. I was shocked at the positive effect that it had on both my lipids and glycemic markers ...and quality of my sleep. (That last one is weird, but I suspect that it fed the gut bugs that help produce serotonin.) The high fiber absorbs fat in the gut and helps with clearance. Through testing I've learned that this doesn't interfere with ketone production so I can still experienced improved cognitive clarity and the stability that comes along with a steady fuel source. One last thought re. clearance issues, are you fasting? How long? For our genotype, I suspect that this is one of our most important strategies. I typically fast for around 16 hours, often more.

I always think of PIR as being associated with higher glycemic markers and notice you didn't check HbA1c this time. That said, based on your LPIR, I suspect that it would be up. Can you check glucose and ketones and try to figure out what's going on? A clue would be high morning FBG along with higher ketones. In the case of true PIR, I suspect that it would be a good idea to switch things up and periodically burn glucose as your primary fuel... i.e. carb nite. Metabolic flexibility, an indicator or optimal health, means that we can seamlessly switch from burning either fat or glucose for fuel. When you stick with primarily burning ketones for a long period, sometimes the body mistakenly assumes starvation and biomarkers go south. Many argue about the significance of this, but I suspect it's worth tweaking as the mixing up of fuel sources correlates with ancestral health.

Have you ever played around to check your body's glycemic response to resistant starches? That might be a good way to enjoy carb night. You'd also be detoxifying while feeding your gut bugs at the same time. A disrupted microbiome is another reason for higher advanced lipids. Lastly, it might be good to rule out any underlying infections, like h.Pylori, which can also have a detrimental effect on lipids.

Finally, if you decide to periodically and purposefully switch your fuel source, journal the differences you feel in cognition, energy, and mood to help determine if a mildly ketogenic diet is providing you with benefit.

[apod]

Hey Dan, if I'm looking at this up right, your total caloric intake of (exercise kcal + net calories after exercise) is often less than 1700 or 1800 calories, with less than 60 grams of protein -- Am I reading this right? (this seems sort of low for exercise days?) Just for reference, what's your height?

Do you practice intermittent fasting?

You might experiment with a couple "nutraceuticals", maybe trading the tocopherols for tocotrienols (cardiovascular research has a good one), maybe with B5 tacked on via pantethine (jarrow has a good one.)

Paul Jaminet has a few interesting articles on high cholesterol in response to changes in diet. Micronutrient intake (choline, copper, iodine, etc) / thyroid hormones / infections seem to have a large effect.

[DanH44]

It's great that you're keeping such detailed records.

Is there any chance there could be another factor that is being overlooked? Is there any other bloodwork or other labs that you get done on a regular basis? I only mention this because I had a doctor briefly mention I might be insulin resistant when I was having blood sugar issues that coincided with huge hormonal swings that I hadn't experienced before (Total estrogen- not individual estrogens, those were in "normal" ranges- and I was not on any hormonal therapies). Have you been feeling any different? Headaches, racing heart, tiredness? I also had one test result with elevated testosterone but that didn't seem to impact my glucose levels. I also stay away from soy because I recognized that when I consumed any, I could get similar symptoms as I did when I knew for sure my hormones were through the roof and were messing with my blood sugar levels.

Also, are you consuming large amounts of olive oil (like in a Mediterranean diet) or anything like turmeric or grape seed extract? I don't know if any of those could affect lab results the way yours are, but just wanted to check. Do you by any chance check your blood sugar levels yourself before and after meals (the same way a diabetic has to)?

Not sure if this helps much, but please come back and post your next results after you make some changes and maybe there will be some enlightening info there.

Hi Noogie, Thank you for your reply!

Of course, this is all so complicated, there's a good chance something else has been overlooked. Beyond diet and genetics, LDL-P is affected by even such things as stress, gut microbes, infection, LPS-providing leaky gut, ... I've got lotsa other bloodwork: regular CBCs, CMPs, plus the usual ferritin, D3, B12, folate, testosterone, thyroid/pancreatic antibodies, Hcy, IGF-1. All these are pretty normal except I have lowish WBCs (always, thought to be good), slightly high anion gap (just the last period - marker for mild ketosis), lowish AST (just this last period), slightly high creatinine (related to heavy exercise).

Towards the beginning of this last experiment period, I experienced legs cramps which was corrected my upping my Mg supp slightly. And starting from when I was fighting off an upper respiratory attack and took some antihistamine on Mar 15, 2017, my sleep which had been excellent at daily fiber >40g, totally deteriorated and never recovered. Other than that, I've felt amazing with really good cognition, lifetime personal bests (at the age of 72) in 1 mile over hilly terrain and weight lifting, all in the last 2 weeks.

Not a lot of OO; instead, I use a lot of high oleic sunflower oil because it has lower SFA. My only supps are the vit E I mentioned, omega-3, TJs CaMgZn, and D3. I check my fasting BG every day and around every meal and exercise unless I'm certain I already know what it will be. BTW, I do test as diabetic on an OGTT, producing very little insulin.

[Julie G]

BTW, I do test as diabetic on an OGTT, producing very little insulin.

Interesting, Dan. Of course this depends on how "low carb" you were, but I'm guessing you're already aware that OGTTs are notoriously inaccurate for low carber's unless you do a 3 day 150+ gram per day carb loading just prior to testing. Did you?

[sylvieJ]

Thanks so much for posting all this detailed information Dan. This was a very informative post and thanks Julie for all the great suggestions and your wise insight.

[DanH44]

Nice to see you posting, Dan. you know I'm not a physician, nor exert of any kind, but I've been following a similar approach for several years and am happy to share a few thoughts. First, congrats on such great record keeping and careful vigilance of biomarkers. You are a role model for us all. My first thought was- a suboptimal thyroid. Then, I saw your TSH . My guess is that you're using medication to upregulate? Good for you.

After ruling that out, I noticed that your SFA intake has slowly risen while your fiber intake has concurrently dropped. It could be that simple. I get around 50 grams of fiber a day from a combo of my vegs and SunFiber, a prebiotic guar gum, recommended by my FMP. I was shocked at the positive effect that it had on both my lipids and glycemic markers ...and quality of my sleep. (That last one is weird, but I suspect that it fed the gut bugs that help produce serotonin.) The high fiber absorbs fat in the gut and helps with clearance. Through testing I've learned that this doesn't interfere with ketone production so I can still experienced improved cognitive clarity and the stability that comes along with a steady fuel source. One last thought re. clearance issues, are you fasting? How long? For our genotype, I suspect that this is one of our most important strategies. I typically fast for around 16 hours, often more.

I always think of PIR as being associated with higher glycemic markers and notice you didn't check HbA1c this time. That said, based on your LPIR, I suspect that it would be up. Can you check glucose and ketones and try to figure out what's going on? A clue would be high morning FBG along with higher ketones. In the case of true PIR, I suspect that it would be a good idea to switch things up and periodically burn glucose as your primary fuel... i.e. carb nite. Metabolic flexibility, an indicator or optimal health, means that we can seamlessly switch from burning either fat or glucose for fuel. When you stick with primarily burning ketones for a long period, sometimes the body mistakenly assumes starvation and biomarkers go south. Many argue about the significance of this, but I suspect it's worth tweaking as the mixing up of fuel sources correlates with ancestral health.

Have you ever played around to check your body's glycemic response to resistant starches? That might be a good way to enjoy carb night. You'd also be detoxifying while feeding your gut bugs at the same time. A disrupted microbiome is another reason for higher advanced lipids. Lastly, it might be good to rule out any underlying infections, like h.Pylori, which can also have a detrimental effect on lipids.

Finally, if you decide to periodically and purposefully switch your fuel source, journal the differences you feel in cognition, energy, and mood to help determine if a mildly ketogenic diet is providing you with benefit.

Hi Julie!

Thanks for the great suggestions. I ordered the SunFiber; should be here on Monday.

I shoot for restricting food intake every day to a 10 hour window, but this has been screwed up lately by the sleep issues I've been having and it's gone up to an ave 12 hr window. Hopefully that fiber will help me get back on track with this.

Yes, I didn't check A1c this time; I was certain it would be 5.2 or better from my glucometer. Although I had very good fasting and PP numbers, my LPIR tells me I was wrong! Maybe my strips were reading low.

I've always been afraid of carb night, because I don't make much insulin and I can't cover it. Never tried it, but from home OGTTs when I was doing low carb years ago, I suspect my PPs will go really high and not come down for hours. And my fasting BG will be high for a few days. Plus, then my glycogen stores will get full and I won't make ketones til it's been depleted. At least , that's my fear. Well, I guess one carb night wouldn't kill me - just to see what it actually does do to my BG. And then we can talk about it. Do you do carb night? How much carb do you take in? I wanna do what you do!

I haven't tried resistant starches. Do you use them? What do you use?

I rule out infection because my WBC is so low.

When you say "periodically and purposefully switch your fuel source", are you thinking carb night or something with a longer period?

[DanH44]

Hey Dan, if I'm looking at this up right, your total caloric intake of (exercise kcal + net calories after exercise) is often less than 1700 or 1800 calories, with less than 60 grams of protein -- Am I reading this right? (this seems sort of low for exercise days?) Just for reference, what's your height?

Do you practice intermittent fasting?

You might experiment with a couple "nutraceuticals", maybe trading the tocopherols for tocotrienols (cardiovascular research has a good one), maybe with B5 tacked on via pantethine (jarrow has a good one.)

Paul Jaminet has a few interesting articles on high cholesterol in response to changes in diet. Micronutrient intake (choline, copper, iodine, etc) / thyroid hormones / infections seem to have a large effect.

Hi apod, Thanks for the input!

Yes, you're right. I want to do better on exercise days, but generally end up doing crappy. I'm 5'3" and at my age my maintenance is calc'd at a bit above 1700. My problem is I'm a little baffled by what to eat on those days to stay ketogenic and stay away from factory farmed shit. I was eating at Chipotle on exercise days before my labs got bad, but I cut that out because I was afraid of possible antibiotics (forgot to mention that when I was listing changes). What do you eat on exercise days?

My IF was a 14-hr window everyday, but that went down the toilet when I started having sleep issues.

I was using the gamma-tocopherol to "abolish" the methylglyoxal produced by a ketogenic diet, so I wouldn't want to give that up unless I give up keto. And the lef brand does include both tocopherols and tocotrienols. Re B5, I take nutritional yeast, so I think I have that covered.

I will read Jaminet. I take thyroid meds. My zinc / copper ratio is 5. What is recommended for apoe4? What do you take on these?

[apod]

From what I understand, pantethine has a different mechanism of action than other forms:
"In multiple clinical trials of patients with elevated cholesterol and triglycerides, total and LDL cholesterol were decreased by an average of 12%, triglycerides decreased by 19%, and HDL cholesterol was increased by 9%"

(From Dr. Atkins, taken with a grain of salt -- "Pantethine's effectiveness at cholesterol lowering has helped cause considerable incredulity among patients as I tell them, with the confidence built on over twenty thousand cases, that they can eat steak, eggs, and butter, as long as they take their pantethine. It encourages the productive of enzymes to break down blood fats and contributes to vitamin E's action against cholesterol buildup. It is one of the few nutrients that increases the amount of omega-3 and reduces clot-promoting fats in cell membranes. By generating more CoA, it enhances metabolism in the heart muscles.") I've also read it decreases oxLDL and increases glutathione.

From what I understand, tocopherols block the uptake of tocotrienols, as far as lipid-lowering action is concerned (https://en.wikipedia.org/wiki/Tocotrien ... terference). Interestingly, I've seen alpha-tocopherol mentioned to increase inflammation in my genetic labs, so I've avoided supplementation.

"High levels of α-tocopherol increase cholesterol production"

I've never been able to make up my mind on whether methylglyoxal is a legitimate concern on a low-carb diet or not (particularly with relatively low A1C) and whether or not to try to tackle this via supplementation (eg. quercetin + resveratrol via Longevinex during the fasted morning or with a meal?)

I would be tempted to try increasing protein and see how that affects BUN / IGF1 and try a little more IF and fiibery carbs with a ketone meter. With a 16-18hr fast between meals, I can get up around 200g of total carbs in with ketones still around 0.3-0.4mmol/L.