MitoLipin - Liquid Saturated Phosphatidylcholine (PC) Mix

[Regina]

Here is my observation thus far. If I put it on my skin it's a kind of wakeful energy. Ingesting it makes me very calm and relaxed and I sleep like a rock. Hope that helps Regina.

Ah cool. Thx for the tip!!

 

[Katty]

Tocopherols are the only solvent in which the saturated PC will dissolve in sufficient concentrations to make it useful. The vitamin E concentration in MitoLipin is a lot less then Progest-E for example, so even though the Progest-E doses are smaller you end up getting about the same amount of vitamin E if you take a common dose of progesterone like 10mg or the daily dose of MitoLipin.
If anybody knows of a solvent that would work for PC other than tocopherols please share. I tried a few of them and only tocopherols dissolved enough PC to make the supplement practically useful.

I see. Guess I'm out of luck for now. Thanks for your response, haidut. I am also wondering if it's actually the PC that's causing the headache and not the Vit E.

 

[Texon]

@haidut
In your opinion is this in any way similar to the effects/benefits of mildronate?

 

[haidut]

@haidut
In your opinion is this in any way similar to the effects/benefits of mildronate?

Higher dose niacinamide is probably closer to mildronate, but vitamin E also inhibits lipolysis. The goal of this supplement is to change the cardiolipin composition and make it more saturated. It may also increase cardiolipin levels but the evidence on that is less settled.

 

[Texon]

Higher dose niacinamide is probably closer to mildronate, but vitamin E also inhibits lipolysis. The goal of this supplement is to change the cardiolipin composition and make it more saturated. It may also increase cardiolipin levels but the evidence on that is less settled.

Interesting. I have tried higher doses of niacinamide but it's a methyl donor antagonist and it also gives me gouty symptoms after a couple of days. My labs that might indicate gout are in the normal range, but when I was tested years ago when trying to enlist for pilot training, they saw something about gout they didn't like and it kept me out. I attributed the results to the fact that, at the time, I was doing some weight training and taking a protein supplement that probably skewed the test. Apart from taking niacinamide, I never really notice these symptoms. Do you think Mildronate is safe to take for someone in generally decent health otherwise, or would the mito supplement make more sense?

 

[haidut]

Interesting. I have tried higher doses of niacinamide but it's a methyl donor antagonist and it also gives me gouty symptoms after a couple of days. My labs that might indicate gout are in the normal range, but when I was tested years ago when trying to enlist for pilot training, they saw something about gout they didn't like and it kept me out. I attributed the results to the fact that, at the time, I was doing some weight training and taking a protein supplement that probably skewed the test. Apart from taking niacinamide, I never really notice these symptoms. Do you think Mildronate is safe to take for someone in generally decent health otherwise, or would the mito supplement make more sense?

I would try both and see which one affects you better. I would also try lower dose niacinamide as it can also improve metabolism without depleting methyl groups too much. The 200mg - 300mg daily dose was shown to not affect methyl balance much.

 

[Texon]

I would try both and see which one affects you better. I would also try lower dose niacinamide as it can also improve metabolism without depleting methyl groups too much. The 200mg - 300mg daily dose was shown to not affect methyl balance much.

Thanks I appreciate these details very much. I am trying the b6 to lower homocysteine by the way. I'll know more in 4 weeks when I have some follow up tests run.

 

[acrylic]

What's the shelf life on this stuff?

Ray has written extensively about the mitochondria and its crucial role in health. The structure and contents of the mitochondria undergo extensive change as part of the aging process and one of the most important constituents of mitochondria is the lipid cardiolipin (CL). CL is crucial for the proper function of complex IV (cytochrome C oxidase) of the electron transport chain, and oxidative metabolism as a whole. In addition, there is evidence that CL is also crucial for the proper functioning of Complex III and V.
Cardiolipin - Wikipedia, the free encyclopedia
"...In mammalian cells, but also in plant cells,[2][3] cardiolipin (CL) is found almost exclusively in the inner mitochondrial membrane where it is essential for the optimal function of numerous enzymes that are involved in mitochondrial energy metabolism."

"...The enzyme cytochrome c oxidase or Complex IV is a large transmembrane protein complex found in bacteria and the mitochondrion. It is the last enzyme in the respiratory electron transport chain of mitochondria (or bacteria) located in the mitochondrial (or bacterial) membrane. It receives an electron from each of four cytochrome c molecules, and transfers them to one oxygen molecule, converting molecular oxygen to two molecules of water. Complex IV has been shown to require two associated CL molecules in order to maintain its full enzymatic function. Cytochrome bc1(Complex III) also needs cardiolipin to maintain its quaternary structure and to maintains its functional role.[15] Complex V of the oxidative phosphorylation machinery also displays high binding affinity for CL, binding four molecules of CL per molecule of complex V.[16]"

Another important function of CL is the activation of the mitochondrial side-cleavage enzyme, which is responsible for the synthesis of pregnenolone from cholesterol.
"...

• Cholesterol translocation from outer to the inner membrane of mitochondrial
• Activates mitochondrial cholesterol side-chain cleavage

..."

Given the importance of CL for proper functioning of mitochondria, it is not surprising that it plays a very important role in both health and disease.

"...Oxidative stress and lipid peroxidation are believed to be contributing factors leading to neuronal loss and mitochondrial dysfunction in the substantia nigra in Parkinson's disease, and may play an early role in the pathogenesis of Alzheimer's disease.[20][21] It is reported that CL content in the brain decreases with aging,[22] and a recent study on rat brain shows it results from lipid peroxidation in mitochondria exposed to free radical stress. Another study shows that the CL biosynthesis pathway may be selectively impaired, causing 20% reduction and composition change of the CL content.[23] It’s also associated with a 15% reduction in linked complex I/III activity of the electron transport chain, which is thought to be a critical factor in the development of Parkinson's disease.[24]"

"...Recently, it is reported that in non-alcoholic fatty liver disease[25] and heart failure[26]， decreased CL levels and change in acyl chain composition are also observed in the mitochondrial dysfunction. However, the role of CL in aging and ischemia/reperfusion is still controversial."

"...Heart disease hits people with diabetes twice as often as people without diabetes. In those with diabetes, cardiovascular complications occur at an earlier age and often result in premature death, making heart disease the major killer of diabetic people. Cardiolipin has recently been found to be deficient in the heart at the earliest stages of diabetes, possibly due to a lipid-digesting enzyme that becomes more active in diabetic heart muscle.[29]"

"...It was first proposed by Otto Heinrich Warburg that cancer originated from irreversible injury to mitochondrial respiration, but the structural basis for this injury has remained elusive. Since cardiolipin is an important phospholipid found almost exclusively in the inner mitochondrial membrane and very essential in maintaining mitochondrial function, it is suggested that abnormalities in CL can impair mitochondrial function and bioenergetics. A study[32] published in 2008 on mouse brain tumors supporting Warburg’s cancer theory shows major abnormalities in CL content or composition in all tumors."

"...Chronic Fatigue Syndrome is debilitating illness of unknown cause that often follows an acute viral infection. According to one research study, 95% of CFS patients have anti-cardiolipin antibodies."


And here are some quotes from Ray that also highlight the importance of CL for mitochondrial function and oxidative metabolism.
Fats, functions and malfunctions.
"...The crucial mitochondrial respiratory enzyme, cytochrome c oxidase, declines with aging (Paradies, et al., 1997), as the lipid cardiolipin declines, and the enzyme's activity can be restored to the level of young animals by adding cardiolipin. The composition of cardiolipin changes with aging, "specifically an increase in highly unsaturated fatty acids" (Lee, et al., 2006). Other lipids, such as a phosphatidylcholine containing two myristic acid groups, can support the enzyme's activity (Hoch, 1992). Even supplementing old animals with hydrogenated peanut oil restores mitochondrial respiration to about 80% of normal (Bronnikov, et al., 2010). Supplementing thyroid hormone increases mitochondrial cardiolipin (Paradies and Ruggiero, 1988). Eliminating the polyunsaturated fats from the diet increases mitochondrial respiration (Rafael, et al., 1984)."

Unsaturated Vegetable Oils: Toxic
"...After weaning, these native fats gradually disappear from the tissues and are replaced by the EFA and their derivatives. The age-related decline in our ability to use oxygen and to produce energy corresponds closely to the substitution of linoleic acid for the endogenous fats, in cardiolipin, which regulates the crucial respiratory enzyme, cytochrome oxidase."

Mitochondria and mortality
"...This fatty acid exposure "decreases glucose tolerance," and undoubtedly explains women's higher incidence of diabetes. While most fatty acids inhibit the oxidation of glucose without immediately inhibiting glycolysis, palmitic acid is unusual, in its inhibition of glycolysis and lactate production without inhibitng oxidation. I assume that this largely has to do with its important function in cardiolipin and cytochrome oxidase."

"...Fewer mitochondrial problems will be considered to be inherited, as we develop an integral view of the ways in which mitochondrial physiology is disrupted. Palmitic acid, which is a major component of the cardiolipin which regulates the main respiratory enzyme, becomes displaced by polyunsaturated fats as aging progresses. Copper tends to be lost from this same enzyme system, and the state of the water is altered as the energetic processes change."

Aspirin, brain, and cancer
"...At birth, the baby's mitochondria contain a phospholipid, cardiolipin, containing palmitic acid, but as the baby eats foods containing poly-unsaturated fatty acids, the palmitic acid in cardiolipin is replaced by the unsaturated fats. As the cardiolipin becomes more unsaturated, it becomes less stable, and less able to support the activity of the crucial respiratory enzyme, cytochrome oxidase. The respiratory activity of the mitochondria declines as the polyunsaturated oils replace palmitic acid, and this change corresponds to the life-long decline of the person's metabolic rate. In old age, a person's life expectancy strongly depends on the amount of oxygen that can be used. When the mitochondria can't use oxygen vigorously, cells must depend on inefficient glycolysis for their energy."

Aging Eyes, Infant Eyes, and Excitable Tissues
"...Cytochrome oxidase is one of the enzymes damaged by stress and by blue light, and activated or restored by red light, thyroid, and progesterone. It's a copper enzyme, so it's likely to be damaged by excess iron. It is most active when it is associated with a mitochondrial lipid, cardiolipin, that contains saturated palmitic acid;the substitution of polyunsaturated fats lowers its activity. Mitochonrial function in general is poisoned by the unsaturated fats, especially arachidonic acid and DHA."


As hinted by one of Ray's quotes above, in order to ensure the proper functioning of the enzyme cytochrome C oxidase, the cardiolipin (CL) must contain saturated fatty acids. If CL has been unsaturated by aging or another process, one way to get it saturated again is to supplement saturated cardiolipin directly. However, that process is unstable and wasteful. As Ray also mentioned, another approach would be to supplement with saturated phosphatidylcholine (PC), which bring saturated fatty acids directly into the CL and re-saturates it back to its state where it was when a person was first born. It is of key importance to note that in order for this process to work, the PC must be saturated - i.e. consist of lecithin linked to one of the saturated fatty acids, with palmitic acid being the most desired. The regular PC sold in stores is high unsaturated and will not only lack beneficial effect but may actually be harmful.
As such, I have decided to release a supplement called MitoLipin containing saturated PC, more specifically dipalmitoylphosphatidylcholine (DPPC) and distearoylphosphatidylcholine (DSPC). Ray has responded to several people over email that if he could fund an affordable source of saturated PC he would probably supplement with it, and suggested doses in the 100mg - 300mg daily, at dinner.
Finally, I would like note that apparent ability of saturated PC to enhance topical absorption of virtually any substance dissolved in it, which is very similar to the properties of DMSO. Thus, applying the supplement (MitoLipin) topically should have excellent absorption, perhaps even better than oral. To enhance the absorption and entry into the cell, the saturated PC is dissolved in tocopherol and MCT. Below is the summarized information about the supplement and some scientific references in regards to its effects.


*******************************************************************************
MitoLipin is a dietary supplement containing fully saturated phosphatidylcholine (PC). The saturated PC supports the function and structure of the mitochondrial lipid cardiolipin (CL). The CL is crucial for the proper functioning of several of the electron transport chain complexes (III, IV, and V) responsible for oxidative phosphorylation. The composition of CL changes with aging and becomes increasingly unsaturated. Saturated PC is believed to change the composition of CL back to saturated, as it is found in humans at birth, and thus restore optimal oxidative metabolism inside the mitochondria of every cell. This product, while consisting entirely of food-grade ingredients, is sanctioned for external use only.

Servings per container: about 30
Serving size: 40 drops
Each serving contains the following ingredients:

Dipalmitoylphosphatidylcholine (DPPC) - 100mg
Distearoylphosphatidylcholine (DSPC) - 100mg

Other ingredients: MCT, tocopherol
*******************************************************************************

References:


Topical Administration:
The skin-permeation-enhancing effect of phosphatidylcholine: caffeine as a model active ingredient. - PubMed - NCBI
The hypocholesterolemic and antiatherogenic effects of topically applied phosphatidylcholine in rabbits with heritable hypercholesterolemia. - PubMed - NCBI
Effects of phosphatidylcholine on the topical bioavailability of corticosteroids assessed by the human skin blanching assay. - PubMed - NCBI

General/Miscellaneous:
Cell membranes and apoptosis: role of cardiolipin, phosphatidylcholine, and anticancer lipid analogues. - PubMed - NCBI
Biochemical effects of phosphatidylcholine treatment in rats. - PubMed - NCBI
Rapid stopping of A23187 action by phosphatidylcholine. - PubMed - NCBI
Blockade of alpha-adrenergic receptors by analogues of phosphatidylcholine. - PubMed - NCBI
The effect of mixed phosphatidylcholine liposomes on beef heart cytochrome c oxidase [proceedings]. - PubMed - NCBI
http://www.sciencedirect.com/science/article/pii/S0006349506725899
Inhibition of mammalian cytotoxic cells by phosphatidylcholine and its analogue
Studies on cytochrome oxidase. Interactions of the cytochrome oxidase protein with phospholipids and cytochrome c. - PubMed - NCBI

Inflammation:
Anti-inflammatory action of a phosphatidylcholine, phosphatidylethanolamine and N-acylphosphatidylethanolamine-enriched diet in carrageenan-induced... - PubMed - NCBI
Anti-inflammatory effects of phosphatidylcholine. - PubMed - NCBI
Protective effect of phosphatidylcholine on lipopolysaccharide-induced acute inflammation in multiple organ injury. - PubMed - NCBI
http://www.ncbi.nlm.nih.gov/pubmed/19215923

Brain/Memory/Mood/Cognition/Nervous system:
http://www.ncbi.nlm.nih.gov/pubmed/25817232
http://www.ncbi.nlm.nih.gov/pubmed/18361742
http://www.ncbi.nlm.nih.gov/pubmed/23979483
http://www.ncbi.nlm.nih.gov/pubmed/21937953
http://www.ncbi.nlm.nih.gov/pubmed/9377589
http://www.ncbi.nlm.nih.gov/pubmed/2938205
http://www.amsciepub.com/doi/abs/10.2466/pr0.1986.58.1.207?url_ver=Z39.88-2003&rfr_id=ori:rid:crossref.org&rfr_dat=cr_pub=pubmed&
http://www.sciencedirect.com/science/article/pii/S0140673683921086
http://www.ncbi.nlm.nih.gov/pubmed/555240

Liver/Gallbladder:
http://www.ncbi.nlm.nih.gov/pubmed/17399847
http://www.ncbi.nlm.nih.gov/pubmed/25775923
http://www.ncbi.nlm.nih.gov/pubmed/25783052
http://www.ncbi.nlm.nih.gov/pubmed/26629827
http://www.ncbi.nlm.nih.gov/pubmed/16550803
http://www.ncbi.nlm.nih.gov/pubmed/15975496
http://www.ncbi.nlm.nih.gov/pubmed/12837851
http://www.ncbi.nlm.nih.gov/pubmed/7539565
http://www.ncbi.nlm.nih.gov/pubmed/24292666
http://www.ncbi.nlm.nih.gov/pubmed/21745592
http://www.ncbi.nlm.nih.gov/pubmed/20832797
http://www.ncbi.nlm.nih.gov/pubmed/8276192
http://www.ncbi.nlm.nih.gov/pubmed/8276177

Gut/Bowel/GI/Endotoxin:
http://www.ncbi.nlm.nih.gov/pubmed/25250596
http://www.ncbi.nlm.nih.gov/pubmed/25477376
http://www.ncbi.nlm.nih.gov/pubmed/18496240
http://www.ncbi.nlm.nih.gov/pubmed/17975182
http://www.ncbi.nlm.nih.gov/pubmed/24796768
http://www.ncbi.nlm.nih.gov/pubmed/18461026
http://www.ncbi.nlm.nih.gov/pubmed/16482629
http://www.ncbi.nlm.nih.gov/pubmed/15951544
http://www.ncbi.nlm.nih.gov/pubmed/15345455
http://www.ncbi.nlm.nih.gov/pubmed/11469682
http://www.ncbi.nlm.nih.gov/pubmed/7493735
http://www.ncbi.nlm.nih.gov/pubmed/23295697
http://www.ncbi.nlm.nih.gov/pubmed/22576006
http://www.ncbi.nlm.nih.gov/pubmed/22100851
http://www.ncbi.nlm.nih.gov/pubmed/21105858
http://www.ncbi.nlm.nih.gov/pubmed/21081908
http://www.ncbi.nlm.nih.gov/pubmed/20926877
http://www.ncbi.nlm.nih.gov/pubmed/20595010
http://www.ncbi.nlm.nih.gov/pubmed/20135022
http://www.ncbi.nlm.nih.gov/pubmed/20048683
http://www.ncbi.nlm.nih.gov/pubmed/19594939
http://www.ncbi.nlm.nih.gov/pubmed/19120061
http://www.ncbi.nlm.nih.gov/pubmed/8430278
http://www.ncbi.nlm.nih.gov/pubmed/8399676
http://www.ncbi.nlm.nih.gov/pubmed/1596725
http://www.ncbi.nlm.nih.gov/pubmed/1289171

Heart/Kidney:
http://www.ncbi.nlm.nih.gov/pubmed/23684996
http://www.ncbi.nlm.nih.gov/pubmed/1420493

Cancer:
http://www.ncbi.nlm.nih.gov/pubmed/17399847
http://www.ncbi.nlm.nih.gov/pubmed/24772432
http://www.ncbi.nlm.nih.gov/pubmed/19579625

Obesity/Diabetes/Metabolism:
http://www.ncbi.nlm.nih.gov/pubmed/25445436
http://www.ncbi.nlm.nih.gov/pubmed/22468042
http://www.ncbi.nlm.nih.gov/pubmed/22145579
http://www.ncbi.nlm.nih.gov/pubmed/21614002

Bones:
http://www.ncbi.nlm.nih.gov/pubmed/19766625
http://www.ncbi.nlm.nih.gov/pubmed/19296835

Anti-viral/anti-bacterial:
http://www.ncbi.nlm.nih.gov/pubmed/9708184
http://www.ncbi.nlm.nih.gov/pubmed/8516563
http://www.ncbi.nlm.nih.gov/pubmed/1570416
http://www.ncbi.nlm.nih.gov/pubmed/1530351

 

[Evgenius]

What would be the difference from this product to taking phosphatidyl choline or sunflower lecithin ?

 

[haidut]

What's the shelf life on this stuff?

Given the fully saturated nature of everything inside it, I'd say at least a year.

 

[haidut]

What would be the difference from this product to taking phosphatidyl choline or sunflower lecithin ?

Did you read the original thread? Most of this is explained in the original post.
MitoLipin is also a phosphatidylcholine (PC) product but it is different from the ones sold at the stores. The regular PC sold in most stores is the unsaturated version - i.e. most often linolic or linolenic acids attached to a PC group. The role of the PC is simply as a carrier but it may have some liver protective effects of its own. As a carrier, it will carry whatever is attached to it inside the mitochondria. So, with the regular unsaturated PC sold in stores you will loading your mitochondria with PUFA, while with MitoLipin you will be loading up with the saturated fats palmitic and stearic acids. The goal is to both stimulate cardiolipin synthesis and change its composition from unsaturated one into saturated one. With regular unsaturated PC you won't be able to do that.

 

[Erica]

What is the source of the tocopherols? Is it derived from wheat germ oil?

 

[haidut]

What is the source of the tocopherols? Is it derived from wheat germ oil?

MitoLipin does not use the wheat germ oil tocopherol as it would make it even more expensive. It uses 98% pure mixed tocopherols from a large US chemical vendor. They do not provide info on the source but it is made in the USA and has certificate of non-allergenicity.

 

[Erica]

MitoLipin does not use the wheat germ oil tocopherol as it would make it even more expensive. It uses 98% pure mixed tocopherols from a large US chemical vendor. They do not provide info on the source but it is made in the USA and has certificate of non-allergenicity.

Great, thank you. Do you believe MitoLipin would somewhat assist in accelerated fat loss?

 

[haidut]

Great, thank you. Do you believe MitoLipin would somewhat assist in accelerated fat loss?

There are human studies with topical PC (which is what MitoLipin contains) helping fat loss. I think the studies are in the original thread. Can't say if it will be effective though.

 

[Waynish]

Curious why it smells so funky - ideas?

 

[tara]

Curious why it smells so funky - ideas?

Smells and tastes delicious to me. :) I have to hold back from eating it.

 

[Texon]

I would try both and see which one affects you better. I would also try lower dose niacinamide as it can also improve metabolism without depleting methyl groups too much. The 200mg - 300mg daily dose was shown to not affect methyl balance much.

Btw I think the b6 you suggested is having a dramatic effect on lowering homocysteine. Last test I had came back at 12.5, and a couple of months before it had shot up to 25 which was a shock. It may have been a one off error because over many years I had never seen it higher than 16. I also tend to eat a lot of honey so that may help bring it down some also. However I have eaten honey for many years, and the TMG and b6 seem to have the greatest effects. Thanks a million for your comments, research and products.

 

[haidut]

Btw I think the b6 you suggested is having a dramatic effect on lowering homocysteine. Last test I had came back at 12.5, and a couple of months before it had shot up to 25 which was a shock. It may have been a one off error because over many years I had never seen it higher than 16. I also tend to eat a lot of honey so that may help bring it down some also. However I have eaten honey for many years, and the TMG and b6 seem to have the greatest effects. Thanks a million for your comments, research and products.

Glad it is helping. Let me know when you retest. The B6 has been used as OTC drug for CVD prevention in many European and Latin American countries for decades and it is likely because of its effects on homocysteine (among others).

 

[RatRancher]

So in general this stuff could be viewed as a PUFA eliminator?
If used long term would it act as a prophylactic if I was less careful in avoiding PUFA?

The concept of getting any part of the organism to resemble it's youth is fascinating.