Dolichol deprivation theory

191 · May 25, 2018, 6:39am

PFS i think. It did seem to help at first with mental sides but it’s stopped working. Not sure if that was placebo or not.

tryingnottoworry · May 25, 2018, 6:39am

I’m sorry you’re feeling worse 19, I really hope you get better soon

Just a quick update, I’m still doing well, and still improving. Libido has gotten better, erectile function is fine, and energy has been well.

I did a little looking into what 19 said about Vitamin A toxicity, and found some interesting information. Vitamin A overload can potentially occur in doses as low as 15,000ui, and one bag of spinach contains roughly 16,000ui. Here’s what wikipedia says about it:

wikipedia:

[Size=4]Vitamin A Toxicity[/size]

Excessive vitamin A consumption can lead to nausea, irritability, anorexia (reduced appetite), vomiting, blurry vision, headaches, hair loss, muscle and abdominal pain and weakness, drowsiness, and altered mental status. In chronic cases, hair loss, dry skin, drying of the mucous membranes, fever, insomnia, fatigue, weight loss, bone fractures, anemia, and diarrhea can all be evident on top of the symptoms associated with less serious toxicity.[35] Some of these symptoms are also common to acne treatment with Isotretinoin. Chronically high doses of vitamin A, and also pharmaceutical retinoids such as 13-cis retinoic acid, can produce the syndrome of pseudotumor cerebri.[36] This syndrome includes headache, blurring of vision and confusion, associated with increased intracerebral pressure. Symptoms begin to resolve when intake of the offending substance is stopped.[37]

If you begin noticing those symptoms, you’ll probably want to start weening off the spinach, as your body may be sensitive to large doses of Vitamin A. Hopefully we’ll be able to find more effective treatments in the future with fewer nutritional drawbacks (potentially Ropren), but in the meantime please be cautious of Vitamin A/Iron overload, and take appropriate steps to minimize your risks.

Here’s an article that was published about 10 days ago. I’m ecstatic that the medical research community is perusing this, and I’d be really interested in reading the full version:

[Size=4]Polyisoprenoids – Secondary metabolites or physiologically important superlipids?[/size]

The polyisoprenoid alcohols (dolichols and polyprenols) are found in all living organism, from bacteria to mammals. In animal and yeast cells polyisoprenoids are derived from the cytoplasmic mevalonate (MVA) pathway while in plants two biosynthetic pathways, the MVA and the plastidial methylerythritol phosphate (MEP) pathway provide precursors for polyisoprenoid biosynthesis. The key enzymes of polyisoprenoid synthesis are cis-prenyltransferases (CTPs), responsible for construction of the long hydrocarbon skeleton. CPTs elongate a short all-trans precursor, oligoprenyl diphosphate, by sequential addition of the desired number of isopentenyl diphosphate molecules which results in formation of a stretch of cis units. Several genes encoding CPT have been cloned from bacteria, plants and mammals. Interestingly, in Arabidopsis, the tissue-specific expression of ten putative cis-prenyltransferases was observed. In contrast to polyisoprenoid phosphates serving as cofactors in the biosynthesis of glycoproteins, glucosyl phosphatidyl inositol (GPI) anchor or bacterial peptidoglycan, the biological importance of polyprenols and dolichols still remains a question of debate besides their function of reservoir of substrates for kinase. These extremely hydrophobic superlipids are postulated to be involved in intracellular traffic of proteins and in cellular defense against adverse environmental conditions. Recent publications show a direct link between the dolichol biosynthetic pathway and congenital disorders of glycosylation (CDG). These discoveries highlighting the cellular significance of polyisoprenoids simultaneously establish the background for future pharmacological interventions. Our mini-review summarizes the results of recent studies on polyisoprenoids.

This reinforces what we’ve been theorizing, and I’m glad to see it’s actively getting studied.

Tpenf · May 25, 2018, 6:39am

Hi TNTW,

Great that you are having such good success with this, I have been following this regime for around a week now and I definitely feel this has given me some improvement in terms of mood, strength, concentration and energy. Not so much on the sexual side i.e ED and numbness. I am currently blending 100gms of spinach with a banana and water once in the morning and again in the evening (200 gms per day aprox).

Could you please detail some things for me with regards to your experience… i.e. quantity of spinach you are eating per day and at what times, type of diet you have besides spinach, are you exercising if so how often? Cardio or weights? Are supplementing at all? Did all your improvements come at once or at different times if so what were the time scales for this? How long have you been on the diet and what percentage of recovery would you say you are at?

I realise we are all different and things will happen in different ways for us all, but for me it would be really handy to have an overview of your regime with a timeline to bench mark against.

Any info you could give would be much appreciated!!

Many thanks.

bluecloud87 · May 25, 2018, 6:39am

What are you guys doing for this? just consuming large amounts of spinach daily?

tryingnottoworry · May 25, 2018, 6:39am

• I was eating one bag a day (170g) of raw uncooked organic spinach about an hour after I woke up.

• I would usually eat salads and other fairly light foods. I drank a lot of tea, avoided greasy food for awhile, and stopped drinking coffee. I’d definitely recommend not drinking alcohol either.

• I didn’t really do any exercise, just daily routines.

• Yes, I’ve been supplementing for quite a while now. Vitamin D3, calcium, magnesium, zinc, omega 3, kelp (iodine), Vitamin C, oil of oregano, and a multivitamin. I’ve dropped some of them from time to time (currently not taking vitamin C aside from what’s in the multivitamin). If you take a ton of supplements at once, make sure you don’t take them on a completely empty stomach or you’ll probably throw up.

• I suppose improvements on the spinach diet didn’t come all at once, and sexual sides seem to always be the last to recover. However my body seemed to respond incredibly fast, and made massive improvements in about a week. Eventually something began to get overloaded (probably either Iron or Vitamin A), and I started to get sick from it. After dropping Vitamin C supplements and weening off of the spinach diet over the course of a few weeks (I’d been on it for a month), my improvements started to (and continue to) return. Please remember that our bodies and circumstances are all different, so don’t expect your body to react in the same way mine did. It’s easy to get discouraged if you don’t see immediate results, but any improvements you make will have to be on your body’s own time.

• From start to finish (including the weeks spent weening off), I was on the spinach diet from March 10th to April 27th.

• At one point (before the overload) I felt about 100%, then dropped down to about 75% (during the overload), and now I think I’m at 99% and climbing. Hopefully I won’t go back down again.

To start, all you need to do is eat a bag (about 170g) of raw uncooked spinach a day, every day. If possible, get organic spinach.

There’s a few recipes you could try with it. I would usually make a salad out of it by adding tomatoes, cheese, honey cured ham, cucumber, croutons, and my favorite salad dressing into a giant bowl (I’d layer the ingredients so I wouldn’t have to mix it). If you’re into cooking you could try blending the raw leaves and adding them into a cold potato soup (just remember not to cook it once the spinach is added). Parsley also contains dolichol, so feel free to experiment with that as well. You can also just eat the spinach leaves plain if you don’t have time to make anything fancy.

Buy enough bags of spinach to last you for a few days, but try not to buy too many at once. Raw spinach doesn’t last too long, and can start to rot in about a week.

If you take Vitamin C supplements, wait about an hour or two before or after eating your spinach because if Vitamin C is in your stomach/intestines at the same time as the spinach, you may start to get abnormally large doses of iron.

Continue eating your spinach once a day for at least a month. When you decide to start weening off, eat about 3/4th of a bag for about 4 days, then 1/2 a bag for 4 days, then 1/4th for 4 days, and finally 1/8th for 4 days.

bluecloud87 · May 25, 2018, 6:39am

Wow, so as it stands, your cured by spinach?

Tpenf · May 25, 2018, 6:39am

Great thanks for getting back to us so quickly, that’s just the info I was after!

Just one more thing could you give an overview of your symptoms before spinach please and to what degree you were suffering? Cheers!

Tpenf · May 25, 2018, 6:39am

Would be helpful if others doing this could post updates too…

tryingnottoworry · May 25, 2018, 6:39am

Potentially, but it’s too early to draw conclusions.

bluecloud87 · May 25, 2018, 6:39am

I am going to go out and buy my first bag of spinach tomorrow. I think if I drizzle over some lemon juice it should be quite tasty. I am not expecting much so I won’t be dissappointed if I get nothing from this but it can only be good for me.

Tpenf · May 25, 2018, 6:39am

Hi again tntw

Was there any reason for drinking the tea whilst on the diet? I noticed you mentiln before to try to avoid caffine. Thanks

gefinauser · May 25, 2018, 6:40am

i have no idea if he took any. either caffee or caffeine alters dolichol somehow which is a no no. im on spinach diet but i know for certain that caffeine induces an adrenal crash on me so i avoid taking anyways.

Exactly.

bluecloud87 · May 25, 2018, 6:40am

I have been munching a bag of spinach for the last 4 days now. Yesterday I felt pretty damn good sexually, but that is probably just a coincidence because today everything has just dropped off again. I am going to keep at it anyway because there is no harm in trying.

191 · May 25, 2018, 6:40am

Is anyone else having any success with this?

Tpenf · May 25, 2018, 6:40am

Yes… Some I think, not to the extent of tryingnottoworry though… would be interesting to get another update from him on how things are no he’s off the diet.

tryingnottoworry · May 25, 2018, 6:40am

Hey guys, sorry for the delayed update. I’ve been doing great, I feel like I’m completely recovered. I’m still skeptical as to whether or not this will be a permanent recovery, but so far things are going great.

I suppose I’ll answer that with a post I made back in February:

Other things were chronic testicle pain, numb penis, cold penis, no pleasure with orgasm, fluctuating thick/watery ejaculate, varying degrees of erectile dysfunction, lack of morning erections, and probably other things as well. I certainly wasn’t at my worst, but I still felt like a shell of my former self.

Caffeine is a phosphodiesterase inhibitor, and phosphodiesterase has an interaction with dolichol further along the n-glycosylation process (Dolichylphosphate-glucose phosphodiesterase).

As far as tea goes, the content of caffeine in tea is usually substantially lower than the amount in coffee and soda (which I have been avoiding), so I doubt it would cause any substantial effects. However I don’t think my body is particularly sensitive to the negative effects of caffeine, so whether or not you drink tea should probably depend on your own body’s reaction to it.

I’d like to re-visit an article I found earlier:

[Size=4]UC San Diego Researchers Find Cause of Metabolic Disease – And Possible Cure[/size]

Monday, July 19, 2010

An international team of scientists, led by researchers at the University of California, San Diego School of Medicine, has discovered the gene mutation responsible for a condition in which eye and brain development is severely disrupted in affected infants.

They also suggest a potential remedy that would involve a simple, daily dietary supplement.

The condition is one of the congenital disorders of glycosylation or CDG, a group of syndromes in which inborn metabolic errors result in serious, sometimes fatal, malfunctions of different organ systems, especially the nervous system, muscles and intestines. Children and adults with CDG have varying degrees of disability, including cognitive impairment and speech difficulties, poor motor skills, vision problems and stroke-like episodes. CDG is rare, but for most of the disorders, there is no treatment.

Writing in the July 15 online edition of the journal Cell, Joseph G. Gleeson, MD, professor of neurosciences and pediatrics at UC San Diego, with Lihadh Al-Gazali, a professor of pediatrics and pathology at United Arab Emirates University, and colleagues discovered that the gene SRD5A3 is responsible for the synthesis of a lipid used by cells as a sugar carrier for protein glycosylation – a complicated, multi-part process in which proteins are modified by the addition of a sugar or sugar chain. Without the added sugars, proteins do not fold or fold incorrectly, resulting in dysfunction and disease.

The UCSD work revealed the molecular basis of an essential, but mysterious, enzymatic reaction in protein glycosylation. “We found the long-sought polyprenol reductase that has been suspected for decades” said Gleeson, a Howard Hughes Medical Institute Investigator who supervised the research. “Using a human genetic approach, we were able to not only find a clue to understand this class of disorder, but also to solve a basic science problem.”

After translation, many proteins are modified with the addition of glycans (polysaccharides or oligosaccharides) that are necessary to help them perform their functions. This modification occurs in a specific cell compartment – the membrane of the endoplasmic reticulum – where the glycans are transported by a lipid before transferring onto proteins.

Dolichol is the lipid carrier for glycans used during protein glycosylation; its availability is critical to accomplishing the modification process, but the synthesis or production of dolichol was poorly understood, especially the last step when polyprenol, a natural long-chain alcohol, is reduced to create dolichol.

“Dolichol is used by the cell like a truck to transport glycans to their destination but also as a support to build them” said Vincent Cantagrel, a UC San Diego postdoctoral fellow and study co-author. “A defect in this transportation results in a less efficient process of glycosylation. Some proteins will miss some glycan chains and will not function correctly.”

In CDG cases, the conversion from polyprenol to dolichol is blocked by a mutation in the SRD5A3 gene. “The mutation is inherited recessively,” said Gleeson. “Both parents must pass along a mutated copy, which is why you don’t see it so much in the US. However, in the Middle East, where marriage of cousins is common, these diseases are much more prevalent.”

Identifying the blockage, Gleeson said, pointed to a possible treatment.

“The key was identifying the enzyme’s role in producing dolichol. This is the basic step that is blocked in our patients, and the disease is the result. Our idea is that if you feed these patients dolichol, that might just treat the condition. It would be similar to giving insulin to diabetics. It’s a simple solution, but one nobody had thought of.”

Currently, artificially produced dolichol is very expensive, mostly because there hasn’t been much demand for it, but the researchers note that the compound is naturally abundant in some plants, such as the gingko or maidenhair tree and spinach. “Ginkgo is already the source of a lot of compounds, so getting dolichol might just mean another step in the extraction process. After that, you could develop a pill that patients could take as a supplement to their diet.”

Gleeson and colleagues are now testing their idea with animal models.

While CDG cases are rare, Gleeson and Cantagrel said their discovery about the polyprenol-dolichol block in the glycosylation process has broader ramifications.

Glycosylation is essential to the normal growth and function of all tissues and organs. “If we look at other steps along the glycosylation pathway, it’s possible we can find other break points,” Gleeson said. “We might be able to treat or cure other forms of CDG or even more common diseases that use this pathway, [Size=4]such as cirrhosis, in which there is deficiency of dolichol.”[/size]

So if our cells are stuck in a loop of inefficient utilization of dolichol due to Finasteride’s inhibiting of SRD5A3 (5-alpha-reductase-type 3), cirrhosis could potentially be a result. Let’s look at what cirrhosis is:

[Size=4]Cirrhosis[/size]

Cirrhosis (pronounced /sɪˈroʊsɪs/) is a consequence of chronic liver disease characterized by replacement of liver tissue by fibrosis, scar tissue and regenerative nodules (lumps that occur as a result of a process in which damaged tissue is regenerated),[1][2][3] leading to loss of liver function. Cirrhosis is most commonly caused by alcoholism, hepatitis B and C, and fatty liver disease, but has many other possible causes. Some cases are idiopathic, i.e., of unknown cause.

Ascites (fluid retention in the abdominal cavity) is the most common complication of cirrhosis, and is associated with a poor quality of life, increased risk of infection, and a poor long-term outcome. Other potentially life-threatening complications are hepatic encephalopathy (confusion and coma) and bleeding from esophageal varices. Cirrhosis is generally irreversible, and treatment usually focuses on preventing progression and complications. In advanced stages of cirrhosis the only option is a liver transplant.

What are some of the symptoms of cirrhosis?

HMMMMMM… sounds pretty familiar. Thoughts?

tryingnottoworry · May 25, 2018, 6:40am

One more thing:

[Size=4]Observation on serum prolactin in hepatic cirrhosis.[/size]

Serum prolactin assays in patients of hepatic cirrhosis were analysed. Patients with cirrhosis had higher values of serum prolactin (27.2 +/- 5.1 ng/ml in males and 38.4 +/- 4.1 ng/ml in females) as compared to control subjects (p less than 0.05). Majority of patients of cirrhosis with suspected portal-systemic encephalopathy had significantly higher serum prolactin than those without encephalopathy (p less than 0.05). Significantly higher values of serum prolactin on admission had positive correlation with mortality (p less than 0.01). Clinico-biochemical severity of hepatic dysfunction was directly correlated with level of serum prolactin. The present study reveals the possibility of diagnostic and prognostic values of serum prolactin in cirrhosis, specially in clinical/sub-clinical subsets of portal-systemic encephalopathy.

So it would appear that increased prolactin could point to cirrhosis being the manifested result of dolichol deprivation, and the higher the value the worse the condition. I wonder how this could relate to us.

bluecloud87 · May 25, 2018, 6:40am

Everyone should get on board just to see if this works for anybody else. I am on my 5th day on the spinach diet, I ate so much yesterday and I’m not feeling very good at all, although I was before today so I am going to carry on.

Xhorndog · May 25, 2018, 6:40am

I eat a decent amount of raw spinach, but I do mix it up with other veggies, lemon, herbs, proteins, etc.

Keep in mind the debate/discussion over raw vs. cooked spinach, proportions, inhibition of iodine & calcium, etc:

weight-loss-center.net/weight_loss_diet_forum/dieting-nutrition/102-raw-spinach-vs-cooked-spinach-one-better-eat.html

(this is just some random site from a google search, but I’ve read about this disagreement on which form is better before; just using it as an example).

191 · May 25, 2018, 6:40am

Could you detail the improvements you have had on spinach? Thanks.

I doubt the cirrhosis idea as this would cause the levels of serum hormones to change - including low testosterone.