Cholesterol - Vitamin D - Carbon Dioxide As Markers For Metabolism

[Ficini]

So I was listening to Danny Roddy podcast with @haidut and he says that cholesterol, vitamin D and carbon dioxide are the best markers to measure metabolism, because you check the input (cholesterol) and the output (vitamin D and carbon dioxide). I find this interesting, but I need some clarification.



So, from what I've understood, cholesterol is produced by the body, after many reactions from Acetil-CoA. On this path, one of the compunds is 7-dehydrocholesterol which is stored in the skin, and later, it will be converted to Vitamin D in the presence of ultraviolet rays. There are 2 paths from Acetil-CoA to Cholesterol (Bloch and Kandutsch-Russell) and the latter contains 7-dehydrocholesterol.

So of course, when the light is not sufficient (living in door and in the winter and not being naked in the sun) the body will try to make more vitamin D, by producing more 7-dehydrocholesterol, which will end up transformed to cholesterol, not to vitamin D.

So the real input is food and the output is more cholesterol when there is too little light exposure.
If you supplement with Vitamin D, will the body make less 7-dehydrocholesterol?

What kind of Carbon Dioxide is @haidut refering to? Is it blood bicarbonate? I know there is an old thread with a huge debate on the way to measure carbon dioxide, but I didn't understand from it if you guys got to a conclusion.

Also how can we interpret the 3 markers?

1. cholesterol low - vitamin D low - bicarbonate low
restricting calories, not enough sunlight, low metabolism

2. cholesterol high - vitamin D low - bicarbonate low
enough or too many calories, not enough sunlight and/or vitamin D supplementation, low metabolism

3. cholesterol high - vitamin D normal - bicarbonate normal
too much food? :)

4. cholesterol low - vitamin D normal - bicarbonate high
that's me...

I consider a level of 40 ng/ml - 25-OH-D as "normal", based on this study.
Defining vitamin D status by secondary hyperparathyroidism in the U.S. population

 

[Steven Bussinger]

These are questions that I've had myself

 

[Ledo]

So I was listening to Danny Roddy podcast with @haidut and he says that cholesterol, vitamin D and carbon dioxide are the best markers to measure metabolism, because you check the input (cholesterol) and the output (vitamin D and carbon dioxide). I find this interesting, but I need some clarification.



So, from what I've understood, cholesterol is produced by the body, after many reactions from Acetil-CoA. On this path, one of the compunds is 7-dehydrocholesterol which is stored in the skin, and later, it will be converted to Vitamin D in the presence of ultraviolet rays. There are 2 paths from Acetil-CoA to Cholesterol (Bloch and Kandutsch-Russell) and the latter contains 7-dehydrocholesterol.

So of course, when the light is not sufficient (living in door and in the winter and not being naked in the sun) the body will try to make more vitamin D, by producing more 7-dehydrocholesterol, which will end up transformed to cholesterol, not to vitamin D.

So the real input is food and the output is more cholesterol when there is too little light exposure.
If you supplement with Vitamin D, will the body make less 7-dehydrocholesterol?

What kind of Carbon Dioxide is @haidut refering to? Is it blood bicarbonate? I know there is an old thread with a huge debate on the way to measure carbon dioxide, but I didn't understand from it if you guys got to a conclusion.

Also how can we interpret the 3 markers?

1. cholesterol low - vitamin D low - bicarbonate low
restricting calories, not enough sunlight, low metabolism

2. cholesterol high - vitamin D low - bicarbonate low
enough or too many calories, not enough sunlight and/or vitamin D supplementation, low metabolism

3. cholesterol high - vitamin D normal - bicarbonate normal
too much food? :)

4. cholesterol low - vitamin D normal - bicarbonate high
that's me...

I consider a level of 40 ng/ml - 25-OH-D as "normal", based on this study.
Defining vitamin D status by secondary hyperparathyroidism in the U.S. population

Good post, surprised it didn't generate interest.

I like the little matrix of markers leading to a speculative outcome at the end. Would be a helpful guide if it could be established even with some anecdotal feedback.

Do you mean for bicarbonate the typical co2 blood labtest commonly available?

I think I am close to == cholesterol high - vitamin D normal - bicarbonate normal.

Yes I force food but in an attempt to keep my weight up. 56 year old lean male.

I am probably going to try some thyroid in an attempt to lower my calorie needs as something is wrong. I eat more now than when I was young and I carried much more muscle then. At least 20 pounds heavier. I wonder if I'm losing glucose via urine although my blood glucose is well in good range.

Cholesterol 215, Vit D 34, Co2 28

I suffer in the northern winters now so this winter taking Vit D. The 34 marker was at the end of this summer

 

[Blossom]

What about all are normal?

 

[Hans]

Good post, surprised it didn't generate interest.

I like the little matrix of markers leading to a speculative outcome at the end. Would be a helpful guide if it could be established even with some anecdotal feedback.

Do you mean for bicarbonate the typical co2 blood labtest commonly available?

I think I am close to == cholesterol high - vitamin D normal - bicarbonate normal.

Yes I force food but in an attempt to keep my weight up. 56 year old lean male.

I am probably going to try some thyroid in an attempt to lower my calorie needs as something is wrong. I eat more now than when I was young and I carried much more muscle then. At least 20 pounds heavier. I wonder if I'm losing glucose via urine although my blood glucose is well in good range.

Cholesterol 215, Vit D 34, Co2 28

I suffer in the northern winters now so this winter taking Vit D. The 34 marker was at the end of this summer

Your cholesterol is actually not high at all. Doctors think that anything over 215 is a concern, but it's not. Studies show that people with elevated cholesterol tend to live longer and be more healthy.
I did an article on interpreting cholesterol lab tests, so maybe it can help you out: How to interpret your cholesterol blood test results to ensure optimal testosterone production and health » MenElite

 

[Hans]

So I was listening to Danny Roddy podcast with @haidut and he says that cholesterol, vitamin D and carbon dioxide are the best markers to measure metabolism, because you check the input (cholesterol) and the output (vitamin D and carbon dioxide). I find this interesting, but I need some clarification.



So, from what I've understood, cholesterol is produced by the body, after many reactions from Acetil-CoA. On this path, one of the compunds is 7-dehydrocholesterol which is stored in the skin, and later, it will be converted to Vitamin D in the presence of ultraviolet rays. There are 2 paths from Acetil-CoA to Cholesterol (Bloch and Kandutsch-Russell) and the latter contains 7-dehydrocholesterol.

So of course, when the light is not sufficient (living in door and in the winter and not being naked in the sun) the body will try to make more vitamin D, by producing more 7-dehydrocholesterol, which will end up transformed to cholesterol, not to vitamin D.

So the real input is food and the output is more cholesterol when there is too little light exposure.
If you supplement with Vitamin D, will the body make less 7-dehydrocholesterol?

What kind of Carbon Dioxide is @haidut refering to? Is it blood bicarbonate? I know there is an old thread with a huge debate on the way to measure carbon dioxide, but I didn't understand from it if you guys got to a conclusion.

Also how can we interpret the 3 markers?

1. cholesterol low - vitamin D low - bicarbonate low
restricting calories, not enough sunlight, low metabolism

2. cholesterol high - vitamin D low - bicarbonate low
enough or too many calories, not enough sunlight and/or vitamin D supplementation, low metabolism

3. cholesterol high - vitamin D normal - bicarbonate normal
too much food? :)

4. cholesterol low - vitamin D normal - bicarbonate high
that's me...

I consider a level of 40 ng/ml - 25-OH-D as "normal", based on this study.
Defining vitamin D status by secondary hyperparathyroidism in the U.S. population

Where is your cholesterol at?
Cofactors needed to create cholesterol include iron, vitamin B2, saturated fat, fructose and biotin (and lots of calories). There are probably more, but that would be a good start. Have you tested anything else, like thyroid, triglycerides, free fatty acids, or HDL and LDL as well?
If bicarbonate is too high, it might be buffering some form of acidity in the body, such as excess phosphate, low calcium, magnesium and/or potassium, excess lactate, etc.
Have you had lactate or PTH tested?

 

[Amazoniac]

So of course, when the light is not sufficient (living in door and in the winter and not being naked in the sun) the body will try to make more vitamin D, by producing more 7-dehydrocholesterol, which will end up transformed to cholesterol, not to vitamin D.

I think that the first adaptation is on pigmentation..
- Skin content of 7-dehydrocholesterol in patients with malabsorption
- Skin content of N-Acetyl-5-methoxytryptamine

If you supplement with Vitamin D, will the body make less 7-dehydrocholesterol?

In cell cultures they odserved that adding atherosclerol reduces the activity of the converting enzyme [7(DH)As → As], which resulted in more 7-dehydroatherosclerol for venom D. However, why would the body shut down 7-dehydroatherosclerol production just because it has enough venom D when it's just a matter of channeling it to atherosclerol synthesis if need'd? That may happen if it builds up locally, but I don't expect it to have a detrimental effect, especially considering the whole-body concentration of each and the means of regulating it that must stop at normalization.

- Cholesterol-mediated Degradation of 7-Dehydrocholesterol Reductase Switches the Balance from Cholesterol to Vitamin D Synthesis

"Cholesterol is an essential molecule for life in higher organisms, but too much or too little can lead to disease. Its synthesis requires a complex series of reactions that involves >20 steps, which must be tightly controlled to balance cholesterol levels. Here, we focus on the post-translational regulation of 7-dehydrocholesterol reductase (DHCR7),2 the terminal enzyme in the Kandutsch-Russell pathway of cholesterol synthesis (1, 2) (Fig. 1A). The alternative terminal enzyme in the Bloch pathway of cholesterol synthesis is 24-dehydrocholesterol reductase (DHCR24) (3). Despite a certain level of redundancy, both the Kandutsch-Russell and Bloch pathways are utilized in different cellular contexts, and are both essential for cell survival (2)."

"In this study we characterized the effect of common SLOS mutations on DHCR7 stability, providing evidence that statin therapy can at least partially reverse the significant loss of DHCR7 expression in SLOS (Fig. 6C). Second, we show that DHCR7 is rapidly turned over, and its degradation is accelerated by cholesterol (Fig. 2), which occurs via the proteasome (Fig. 7A). We demonstrate that this mechanism acts as a switch to increase vitamin D synthesis as a consequence of 7DHC accumulation (Fig. 8C). Thus, DHCR7 plays a unique role in regulating both cholesterol and vitamin D levels in the cell."

"Our study also provides new biochemical evidence connecting DHCR7 and vitamin D. Genetic variants in DHCR7 are reliably associated with vitamin D status (13, 14), indicating that the enzyme plays an important role in vitamin D metabolism. This variation in DHCR7 has been identified as a major adaptation affecting vitamin D metabolism in recent evolutionary history. Kuan et al. (56) determined that the strong selective pressure exerted by polymorphisms associated with DHCR7 assisted early human migration into areas of low sunlight by providing protection from the effects of low vitamin D. However, little was previously known about the biochemical nature of this relationship between DHCR7 and vitamin D. A recent study identified that vitamin D can inhibit DHCR7 activity (57), which suggests that a feed-forward mechanism for vitamin D production could exist. Our data extend this by demonstrating that vitamin D can impede cholesterol synthesis by specifically reducing DHCR7 protein expression in a dose-dependent manner (Fig. 8A). The skin predominantly utilizes a modified Kandutsch-Russell pathway (2), indicating that the pathway can provide a constant source of 7DHC for the production of vitamin D (58). In addition, the highly labile nature of DHCR7, destabilized further by cholesterol, also serves to switch flux toward vitamin D synthesis (Fig. 8C). Therefore, our findings uncover a new control point in cholesterol synthesis that also regulates vitamin D production, with DHCR7 playing a critical role in the homeostasis of two important molecules that are involved in human health and disease."​

↳ [56] DHCR7 mutations linked to higher vitamin D status allowed early human migration to Northern latitudes

"7-dehydrocholesterol is found in high concentrations in the epidermis [24]. Chen, et al. showed that the conversion of epidermal 7-dehydrocholesterol in hypopigmented skin is much more efficient than in highly pigmented skin. This suggests that sufficient previtamin D3 can be synthesized in Caucasians but not in people with heavily pigmented skin after a brief exposure to summer noon sunlight even at high latitudes [25]. Dependency upon sunlight for vitamin D synthesis may also explain why 7-dehydrocholesterol levels are three to eight times higher in non-feathered skin areas of birds such as the legs and feet when compared to body skin which is covered with feathers [26]."

"These studies show that humans and animals have adapted mechanisms to exploit optimal methods of synthesizing vitamin D in response to their environment. The increased frequencies of DHCR7 alleles associated with higher vitamin D status in the hypopigmented populations of Europe and Northeast Asia may represent yet another adaptation which conferred a survival advantage allowing early humans to avoid severe deficiency when migrating to northern latitudes."​

 

[Ficini]

Where is your cholesterol at?
Cofactors needed to create cholesterol include iron, vitamin B2, saturated fat, fructose and biotin (and lots of calories). There are probably more, but that would be a good start. Have you tested anything else, like thyroid, triglycerides, free fatty acids, or HDL and LDL as well?
If bicarbonate is too high, it might be buffering some form of acidity in the body, such as excess phosphate, low calcium, magnesium and/or potassium, excess lactate, etc.
Have you had lactate, or PTH tested?

Hey, Hans!
Thank you for your response.

Cholesterol 123 mg/dL
Triglycerides 87 mg/dL
PTH 67 pg/mL
25-OH-D 36.1 mcg/L
TSH 0,138 mUI/L

Usually I eat about 3000 calories, very peaty (milk, fruits, cheese, liver, gelatin, carrot, coconut oil, butter) .

What I don't like is that my leukocytes are high 9640 (maximum being 10200) and eosinophils are 1720 /mm3, (maximum being 550).
Probably my body is being rebuilt after 7 years of veganism, mostly raw. I quit that life style 14 months ago and I'm peating for 8 months now.

 

[Hans]

Hey, Hans!
Thank you for your response.

Cholesterol 123 mg/dL
Triglycerides 87 mg/dL
PTH 67 pg/mL
25-OH-D 36.1 mcg/L
TSH 0,138 mUI/L

Usually I eat about 3000 calories, very peaty (milk, fruits, cheese, liver, gelatin, carrot, coconut oil, butter) .

What I don't like is that my leukocytes are high 9640 (maximum being 10200) and eosinophils are 1720 /mm3, (maximum being 550).
Probably my body is being rebuilt after 7 years of veganism, mostly raw. I quit that life style 14 months ago and I'm peating for 8 months now.

Yeah cholesterol is very low. Trigs are fine. PTH elevated and vit D on the low end. PTH increases calcium and phosphate mobilization from bone and increases the excretion of bicarb making you more acidic. PTH also promotes inflammation and is elevated in autoimmune conditions.
Cortisol, serotonin, estrogen and prolactin all stimulate PTH secretion.
The PTH could also be high because of the low D.
TSH is really low. Are you using thyroid?
The elevated WBC could be due to the elevated PTH or endotoxins. Have you had your hsCRP tested?

 

[Ficini]

hsCRP is fine 0,4 mg/dL.
Prolactin is 7.87 ng/ml
That's why it looks weird to me that only eosinophils are high and not other inflammation markers.
I do take thyroid.
I believe PTH is high due to low D. The vitamin D level is after 3 months at the tropics :))
I supplement with vitamin D, E, A on the skin.
Occasionally I take Aspirin/K2 and B1 and B2.

Thank you again for your answer, you have a great blog, I've been following you on Instagram for a while.

 

[Hans]

hsCRP is fine 0,4 mg/dL.
Prolactin is 7.87 ng/ml
That's why it looks weird to me that only eosinophils are high and not other inflammation markers.
I do take thyroid.
I believe PTH is high due to low D. The vitamin D level is after 3 months at the tropics :))
I supplement with vitamin D, E, A on the skin.
Occasionally I take Aspirin/K2 and B1 and B2.

Thank you again for your answer, you have a great blog, I've been following you on Instagram for a while.

Thanks man!
hsCRP is below 0.5 so that's good. Prolactin is good.
A low protein diet (vegan) can lead to low mTOR and elevated AMPK and AMPK suppresses cholesterol synthesis. Upping mTOR and IGF-1 could greatly help to increase cholesterol. So maybe you just have to give it time and cholesterol should increase as you stick to this new diet. If it doesn't, upping fructose and saturated fat might help.

3 months in the tropics sound nice...and hot lol. Cholesterol in the skin is necessary for vit D synthesis so your low overall cholesterol could explain the low D even with lots of sun. Supplementing with D could be a good idea for now to up your D levels and low PTH.

 

[Ficini]

I give up on the winter. Next week I move back to the tropics.
With red light, vitamin D supplementation and peaty diet, this winter in Europe was one of the best I can remember, but still there is no replacement for the real thing. :)

 

[Ficini]

I've got stuck in Sri Lanka for 7 months. While being there, I've fixed my 25 OH D - 58,3 mcg/L (was 36.1 before) and PTH 38.6 pg/mL (67 before). My eosinophils got down from 1720 /mm3 to 980, but they are still high, normal being 320.
I still wasn't able to significantly rise my cholesterol. It is now 146 (123 before).

 

[Stilgar]

Has anyone been able to significantly raise cholesterol? Mine has been stuck at 130-160 for the last couple of years. My vitamin d is usually good, perhaps a little low but it doesn’t take me much to raise it to 40-50 if it drops, whereas my partner who usually has a cholesterol of 200 or so struggles to get a good vitamin d level.

I still take a quarter of cynoplus at night and try to eat sugar in favour of starch, but switching these about or increasing amounts rarely changes much. I’ve spent the last month in all day sun and I’ve had noticeable low cholesterol symptoms (numbness, worse digestion, up and down mood, lowered libido). Maybe it’s time to finally drop the thyroid to get it up.

My cholesterol level has been my nemesis so I find this thread very interesting- thanks.

 

[Murtaza]

Has anyone been able to significantly raise cholesterol? Mine has been stuck at 130-160 for the last couple of years. My vitamin d is usually good, perhaps a little low but it doesn’t take me much to raise it to 40-50 if it drops, whereas my partner who usually has a cholesterol of 200 or so struggles to get a good vitamin d level.

I still take a quarter of cynoplus at night and try to eat sugar in favour of starch, but switching these about or increasing amounts rarely changes much. I’ve spent the last month in all day sun and I’ve had noticeable low cholesterol symptoms (numbness, worse digestion, up and down mood, lowered libido). Maybe it’s time to finally drop the thyroid to get it up.

My cholesterol level has been my nemesis so I find this thread very interesting- thanks.

same boat as you. my cholesterol has been below 130 for a few years now so would like to know what could be the issue here. my best guess is that my liver function is impaired due to taking accutane when i was a teenager.

 

[Stilgar]

same boat as you. my cholesterol has been below 130 for a few years now so would like to know what could be the issue here. my best guess is that my liver function is impaired due to taking accutane when i was a teenager.

Ah! Woe is us. Have you got gut issues too out of interest?

 

[Murtaza]

Ah! Woe is us. Have you got gut issues too out of interest?

i did have gut issues up until two months ago. couldnt digest milk and starchy meals gave me lose stools. taking two tbsps of gelatin after every meal has fixed that.

 

[lampofred]

I've had low cholesterol for a while, my current guess is that calcification may something to do with it. I think a manual way to lower calcification is inhale a full breath of air thru one nostril, retain it for as long as possible, and breath out the other nostril, alternating nostrils. As you are able to retain for longer it means your vessels are opening up and getting less calcified. But thyroid/coffee and liver/eggs are probably the RP recommended way to lower calcification.

 

[Ficini]

My interpretation of my results is that the body needs a bigger quantity of cholesterol to recover from 7 years of starvation (raw veganism) and no matter how much I eat (I eat lots of calories from sugar and saturated fat) it is still not enough or the body is still not able to produce enough cholesterol. I guess the eosinophils could be needed to clear dead tissue.

Anyways I never thought about calcification as a reason for low cholesterol, but it seems plausible. I believe I have this issue and I plan a high K2 (MK4) protocol, hoping to solve my tinnitus. My tinnitus was lowered after peating for one year, but it still comes louder sometimes.

 

[gaze]

"As far as the evidence goes, it suggests that coconut oil, added regularly to a balanced diet, lowers cholesterol to normal by promoting its conversion into pregnenolone. (The coconut family contains steroids that resemble pregnenolone, but these are probably mostly removed when the fresh oil is washed with water to remove the enzymes which would digest the oil.) Coconut-eating cultures in the tropics have consistently lower cholesterol than people in the U.S. Everyone that I know who uses coconut oil regularly happens to have cholesterol levels of about 160, while eating mainly cholesterol rich foods (eggs, milk, cheese, meat, shellfish). I encourage people to eat sweet fruits, rather than starches, if they want to increase their production of cholesterol, since fructose has that effect."

- Ray peat

Are you guys sure 160 cholesterol is that low @Stilgar ? Ray seems to say people he knows with a good metabolism have a cholesterol of 160 from high turnover to pregnenolone. 130 however is indeed quite low, so depends where you are between 130-160. Those symptoms you mention could be something other than cholesterol, like Vit A deficiency (which is also related to cholesterol)