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[NeoV]

--Diabetes of the Penis: Peyronie's and Diet--Introduction

Insulin resistance, hyperinsulinemia, and hyperglycemia (high blood sugar) lead to increased levels of tgf-beta, myostatin, reactive oxygen species (ROS), mitochondrial disorder, FOXO3, and decreased nrf2, glutathione, and a weaker endogenous antioxidant system, therefore causing fibrosis and Peyronie's disease. It also increases histone deacetylase (HDAC) which is heavily implied in fibrosis. YOUR BLOOD SUGAR MEANS NOTHING, you can have hyperinsulinemia which takes place before detectable pre-diabetes, and suffer dire consequences. This is not tested for and does NOT show up on a blood sugar test.

Unsurprisingly. Peyronie’s and Dupuytren's are more common in those with Diabetes, and statin drugs are known to cause Peyronie’s and diabetes while lowering CoQ10 levels. You can be skinny, fit, and muscular and still have insulin resistance. It has only been in recent years that diet has been shown to reverse diabetes type 1 and 2, and with Alzheimer's now being called “Diabetes type 3,” and fasting shown to have a great effect against cancer, we have every right to take the role of blood sugar and Peyronie’s as serious as ever. Insulin resistance and the overconsumption of carbs, not fat, is now being established as the leading cause of heart disease and other organ damage, and penis disease should be no exception.
*an explanation of how hyperglycemia leads to fibrosis and a raise in tgf-beta can be seen here.
 

A personal anecdote: At 24 years old, I started to develop Peyronie’s, neuropathy, and tendon pain at the exact same time. My penis, hands, and feet began to go numb, and my father with Peyronie's also has the same symptoms. At age 30, my nerve pain became severe, and after recent brain and body scans and extensive blood work, the only finding was “slightly high blood sugar.” I recently got sick and did not eat much of anything for 3 whole weeks, and my nerve pain disappeared and my Peyronie’s looked and felt great. Upon starting a carb heavy diet and stopping CoQ10, my nerve pain came back with a vengeance. Doing some digging around online, it appears that even slightly raised blood sugar levels can damage blood vessels and nerves, while the general guidelines on what is low or high may be completely wrong. Upon re-starting CoQ10 and going mostly ketogenic, my Peyronie’s is doing the best that it has in years and the feeling in my hands and feet are coming back. UPDATE 2018, I now have NO nerve pain and my Peyronie's is better than ever, following a strict ketogenic diet. I am unable to eat pizza or pasta or anything without nerve pain.
 
The Diet
 
Goals - to prevent fibrosis via the below means:
*Inhibit histone deacetylase to deactivate the genes related to Peyronie and fibrosis.
*activate nrf2 pathway (to reduce tgf-beta) -- > decrease tgf-beta and myostatin.
*increase mitochondrial function, improve insulin sensitivity
*decrease reactive oxygen species and inflammation
 
The Base
Ketogenic or low carb diet / fasting
Deactivates histone deacetylase and the gene behind Peyronie's, and activates nrf2 pathway, reduces tgf-beta, significantly improves mitochondrial function, reduces inflammation, restores insulin sensitivity, increases blood viscosity, while fasting states induce scar reduction through autophagy.
 
CoQ10 - 300 mg / day (reduce tgf-beta, myostatin, restores insulin sensitivity, reduce ROS and fibrosis)
Alpha Lipoic Acid - (reduce tgf-beta, myostatin, restores insulin sensitivity, reduce ROS and fibrosis)
Creatine Monohydrate - 2 - 5g / day - significantly blocks myostatin and boost mitochondrial health
Broccoli and Cabbage - sulforaphane in these vegetables significantly block histone deacetylase and myostatin.
Caffeine - (a xanthine derivative like pentox that reduces tgf-beta and fibrosis, use within safe limits)
Coffee - Chlorogenic acid reduces fibrosis, ROS,
Green Tea - EGCG blocks myostatin, reduces ROS, fibrosis. Studied at length.

Avoid: Refined carbohydrates and sweets. Never combine refined carbs with saturated fat. Pizza is one of the worst offenders. Save it for special occasions or eliminate. I ate a diet of just cabbage and for six months and continue to eat extremely low carb and moderate fat. Finally now I eat only eggs, meat, and some very low glycemic veggies if any veggies at all.

Do: Exercise, meditate, and drink plenty of water, and keep something on hand to eat if you get low. If you are to eat the “classic” carbs, go for complex or slow digesting carbs.
 
Tips and Warnings
 
Budget and Food Choice
Replace rice, bread, or pasta with cabbage at every meal. Shredded cabbage, meat, and eggs, drenched in olive oil, is a calorie and nutrient dense meal you can always rely on. Go crazy on veggies and buy in bulk frozen. Olive oil and coconut oil is your best friend on a ketogenic or low carb diet. Eggplant is another heavy veggie to go for in place of the classic carbs.

Fats
Extra virgin olive oil, extra virgin coconut oil, and butter are the most stable for cooking. Do not consume vegetable oils. MCT oils are very useful for avoiding hypoglycemia and getting into ketosis.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2671041/
 
Supplement withdrawal (CoQ10, and others)
Upon stopping this supplement, one’s supply will lower below baseline for a short while, possibly even a week. This may be extremely dangerous, and despite no issues ever being documented, I think it’s best to slowly wean yourself off it, instead of suddenly stopping 300mg per day. Your body needs to begin to create the nutrient again. That being said, temporary states of low CoQ10 may not be a real issue, but I still find the idea troubling.
 
**Always consult with a healthcare professional when changing your diet drastically**

[Tychy]

I just discovered alpha lipoic acid, be sure to read the dosage warning on that one:
https://examine.com/supplements/alpha-lipoic-acid/

[Paolo]

Guys, for vegetarian lovers ALA can be found in flaxseed, chia seed and hemp.

ALA may increase nerve regeneration rates and be of aid to nervous system injuries, from the symptoms of tingling, burning, and itching.

What makes ALA special is that since it is both water and fat soluble, you are able to absorb it at any time, regardless of what you’re eating or drinking with it, it crosses also the blood brain barrier (BBB) also, one of the few antioxidants to do so.

Taking an ALA supplement once every 3 to 6 hours would be preferable over a higher dose that’s once or twice daily, for example 100mg pill for systemic administration

Morning: 1 pill upon waking
Mid-morning 1 pill
Lunch: 1 pill
Mid-afternoon 1 pill
Dinner: 1 pill
Late evening 1 pill
Total = 600mg

[JayGould]

Have you heard about YK-11? It's supposed to be the strongest myostatin inhibitor available. Safety profile unknown however as it is a very new substance.

[Tychy]

YK-11 is a synthetic, steroidal selective androgen receptor modulator (SARM) (...)
The drug has anabolic activity in vitro in C2C12 myoblasts and shows greater potency than dihydrotestosterone (DHT) in this regard.

That just sounds unsafe. I would advise not to try anything like that without the guidance of a clinical andrologist.

[NeoV]

Jay, Myostatin is a major driver of fibrosis and a member of the tgf-beta family. Myostatin is found in the Peyronie's penis and plaques (2008 study). I would love to get my hands on some Follistatin, or what you listed. Until then I'll be eating whole eggs, taking creatine, and coq10. Multiple studies show a reversing of fibrosis when Myostatin is blocked.

I may be dreaming, but my scars are softer and my ridges lesser now that I've been taking that supplement combo for a month or so. I also advise anyone to stick to veggie caps. I would love some input on this. Does anyone know which is better in general, veggie caps or soft gels?

Thanks Paolo! One of the only times my nerve pain went away was when I was eating less and taking ALA and CoQ10. I'll be buying it again!

[Paolo]

NeoV, not for the first time your post was most interesting, particularly about Follistatin, to that end I hope the below link interests you somewhat;

https://examine.com/nutrition/does-dark-chocolates-epicatechin-content-promote-muscle-growth/

Dark chocolate should be raw and unprocessed as much as possible, don't drink chocolate with milk as milk peptides ruin its antioxidant effects greatly, it's not that pleasant but I now prefer it that way, you get used to it.

On a separate note I have just started supplementing Broccomax (Broccoli extract).

Thanks for this 

[skunkworks]

Myostatin is found in the Peyronie's penis and plaques (2008 study).

Could you link to that study?

It's only quite recently that myostatin was proven to be in smooth muscle at all, and only a few papers on it so I'd really like to see that paper.

Edit. Nvm, I could try being non lazy and find it myself: http://www.jsm.jsexmed.org/article/S1743-6095(15)32106-8/fulltext

Interesting read, bloody myofibroblasts at it again.

This study seems to support our daily pde5 recommendation - https://www.nature.com/ijir/journal/vaop/ncurrent/pdf/ijir201722a.pdf?origin=ppub

[Stabler]

Hi guys,



I would just like to clarify something, there is no diet that will reverse Type 1 diabetes. Type 1 is acquired as a child and when the pancreas no longer  has the ability to produce insulin. There is no diet that will make it produce insulin again.

Also the Ketogenic diet can be very dangerous if not followed by a physician. this diet has your body using its own fats as energy causing your body to produce/spill ketones in the urine which if not monitored can cause coma and death. Now this is not to say that No one should try it however if you are in this forum it is because you have a weakened immune system and compromising it more could be unwise. So please be careful

Stabler67

[skunkworks]

A ketogenic diet or near ketogenic is (in my opinion) one of the most beneficial ways of eating you could follow as a Peyronie's sufferer.

I recall three case studies where type 1 diabetes was reversed in a juvenile with a gluten free diet, eg - https://www.ncbi.nlm.nih.gov/pubmed/22729336. In an adult, I'd agree, is it almost certainly past the point of dietary intervention with regards to no longer requiring treatment. But you can use diet reduce how much medication you need day by day.

Type 2 diabetes is obviously reversible, quite easily in fact.

The 'dangers' of a ketogenic diet have been hugely exagerrated in the media, usually due to incorrectly conflating ketoacidosis with ketosis. They had been used safely for decades to effectively treat epilepsy before the weight loss and health benefits were rediscovered. Before that, we have many hundreds of thousands of years in which humans lived in a ketogenic state almost every hour they were alive.

The ketogenic state is more natural for the human body than being in a non ketogenic state. Before agriculture we would have been in a ketogenic state for 99.99% of the hours in our lives.

For 99.4% of our existence from homo erectus onward, we have been hunter gatherers and existing in a ketogenic state.

The best diet you can eat will be eggs, grass fed beef and wild caught fish, with vegetables as a small side.

[Tychy]

The best diet you can eat will be eggs, grass fed beef and wild caught fish, with vegetables as a small side.

The best diet you can get is a diverse mix of unprocessed foods, tackling all the necessary minerals, vitamins, proteins and fats your body needs. We have a bit evolved from our ancestors in terms of energy consumption Other than that, totally agree. Ketogenic diet felt great. You don't have to go full scale no-carb. There are several approaches available with low-carb that work to keep you in a mostly ketogenic state.

[NeoV]

Sorry for not providing that study. It is interesting that tgf-beta gets attention and not myostatin, which IS part of the tgf-beta family, and is clearly linked to fibrosis and other issues.

Indeed, as Stabler has said, always be careful when changing your diet and consult a doctor.

When I go low carb I can feel very sick and have panic attacks and nearly pass out. I was never like this until recently, but now heavy carb meals cause this as well. I assume that's because my blood sugar crashes. Now that I eat very low carb and high fat, I don't have panic attacks. If I do go too low, I will eat something a bit sweet and even bough glucose tablets. Experiment and always keep something to eat on hand. If you have Peyronie's, chances are you HAVE some blood glucose issues as well.

I do agree that humans are not meant to eat many carbs, like any other animal. I appreciate the comment Skunkworks!

[skunkworks]

It would be VERY interesting to see HbA1c results for a big section of Peyronie's sufferers.

And yeah, you can quibble about the minutae of diet endlessly. As long as processed sugars and grains are gone and carbs are low, you'll be doing way better than most.

[Tychy]

They did HbA1c during my active phase. I even had the whole expensive blood work done, because that was a prequisite for therapy. It was normal. The only values off were VitD, which was on the lower end of the scale and uric acid a bit high, but still not in range of gout.

[Paolo]

Tychy, Your Vitamin D comment is interesting

Transforming growth factor beta-1 (TGF-β1) plays a major role in the pathogenesis of Peyronie's disease (Peyronies Disease). Vitamin D modulates the profibrotic effects of TGF-β1, as shown in recent studies. Therefore, vitamin D deficiency might be a contributing factor in the pathogenesis of Peyronies Disease

I will have to research this more, i.e. toxic dosage etc, thanks 

[NeoV]

Tychy, I wonder what "normal" was for the HbA1c. I ask this because from what I read, the standard "normal" is basically already causing damage to your organs. On the extreme side, Dr. Bernstein, says you need a HbA1c of 4.2 to 4.6 or you'll be causing damage.

[Crooked_Stick]

my HA1C was 5.7 (pre-diabetic) during the active phase...also my vitamin D was at the bottom of the normal range and my T was low, all pre-conditions for Peyronies Disease

[NeoV]

That's great info Crooked.

My ha1c was only 5.3 earlier this year, with 114 blood sugar, which I believe was fasting, in which case it is very much pre-diabetic. I broke my ketosis yesterday and immediately felt sick with a reactive hypoglycemic episode. I felt dread and panic for hours afterwards and my face and tongue went numb.

I have to say, I am very happy I now know the cause of my nerve pain and numbness, AND my panic attacks. It was never a panic disorder, it was merely an issue or problem with blood sugar. For years I spiked it and let it drop too low.

[Tychy]

Now this is interesting! I was obviously referring to lab reference ranges. Do you have a study or something for me to read? As you've provoked it, have my lab sheet

Name:  Value (Reference Range)

HbA1c: 5.1% (4-6)
HbA1c: 32 mmol/mol (20 - 42)

TSH: 0.73 mIE/ml (0.3 - 4.2)
FT3: 4.08 Dmol/l (3.3 - 6)
FT4: 12.7 Dmol/l (7 - 21.1)
TPO-AK: 1.1 IU/ml (0-35) (No Hashimoto)
TRAK: <0.1 IU/ml (0-0.1) (No Morbus Basedow)
Parathormone: 39.7 pg/ml (12-88)
ACTH: 11.5 ng/l (5-60) (Seems I'm not under chronic stress, well...)
Total protein: 6.86 g/dl (6.6-8.3)
GOT: 23 U/l (0-50)
GPT: 24.6 U/l (0-50)
GGT: 17.4 U/l (0-54.9)
Alkaline Phosphatase: 56.9 U/l (30-120)
LDH: 173 U/l (208-378) (Significant for cell turnover (death). It's lower than reference, which means less cells are dying than usual? I suppose that's good)
Bilirubin: 0.57 mg/dl (0-1.19)
Creatinine: 0.93 mg/dl (0.72-1.18)
Uric acid: 7.76 mg/dl (0-7) (I have occasional pain in my hallux and was thinking about gout, but treatment-worthy is 8 or above)
Inorganic Phosphates: 3.09 mg/dl (2.6-4.5)
Iron: 83 µg/dl (70-180)
Calcium: 2.48 mmol/l (2.2-2.65)
Potassium: 4.42 mmol/l (3.5-5.1)
Natrium: 140 mmol/l (135-145)
Magnesium: 0.78 mmol/l (0.73-1.06)
Haemoglobin: 15.4 g/dl (13.5-17.8 )
Erythrocytes: 4.9 M/µl (4.4-5.93)
HKT: 0.45 I/l (0.47-0.53) (I just saw this. Low HKT and iron, though not clinical significant, is sign of Anemia. Ery also in low range )
HBE: 31.5 pg (28-33)
MCV: 92.5 fl (80-96)
MCHC: 34 g/dl (33-36)
Leucocytes: 5.4 k/µl (3.9 - 10.9) (stopping smoking helps! this was usually up to 9)
Thrombocytes: 314 k/µl (140-330)
Vit-D-25-OH: 23.5 ng/ml (30-100) (I did supplement D3 5000 IU once daily for a month after the test)
Folic acid: 6.2 ng/ml (4-20)
Vitamin-B12: 352 pg/ml (180-914)
Ferritin: 43.1 ng/ml (20-200) (well, look. It's also low)
Luthenizing hormone: 2.21 U/l (4-10)
FSH: 5.64 U/l (1.27-19.3)
Estradiol: 23 pg/ml (0-50)
Prolactine: 5.1 ng/ml (5-15)
Testosterone: 3.81 ng/ml (2.7-10.7) (I've asked my uro about this. You'd want to test receptor activity, as low T may be well bound. It's basically different for everyone)
Inhibin_B: 161 ng/l (25-325)
SHBG: 44.7 (13.2-89.5)
Free androgen index: 29.5 (15-95)
Cortisol: 88 ng/mg (50-250)

...and be sure, I'll NEVER type this off this sheet again
I suppose my wheat allergy is/was causing malabsorption

[Tychy]

@Paolo:
This was one of the reasons to think about Ehlers-Danlos-Syndrome...Hypermobility and vascular type has mutations on genes that is relevant for TGF-β1 (COL3A1 to be specific, TNXB). And it would fit with the other symptoms:
https://omim.org/entry/130020

Overall, those with classic EDS and TNX-deficient EDS reported the most neuromuscular involvement, with muscle weakness, hypotonia, myalgia, easy fatigability, and intermittent paresthesias, although patients in all groups reported these features. Physical examination showed mild to moderate muscle weakness (85%) and reduction of vibration sense (60%) across all groups. Nerve conduction studies demonstrated axonal polyneuropathy in 5 (13%) of 39 patients. Needle electromyography showed myopathic EMG features in 9 (26%) and a mixed neurogenic-myopathic pattern in 21 (60%) of 35 patients. Muscle ultrasound showed increased echo intensity in 19 (48%) and atrophy in 20 (50%) of 40 patients. Mild myopathic features were seen on muscle biopsy of 5 (28%) of 18 patients. Patients with the hypermobility type EDS caused by TNXB haploinsufficiency were least affected. Voermans et al. (2009) postulated that abnormalities in muscle or nerve extracellular matrix may underlie these findings.

I've bolded the things that I'm currently or transiently having.

My mother has expressed some of the same symptoms, especially low blood pressure and she's now in her 60s. As Ehlers-Danlos is always inherited without mutating (Type 3 will always pass down type 3), type IV is unlikely for me. Life expectancy with type IV is 34 for men and 37 for women.
I do have a tendency for bruises and my mother once had a chiropractic treatment where her whole right shoulder was blue from rupturing a blood vessel.....I have to get this on the list to be diagnosed, though I know what my doc is going to say....

[Paolo]

Tychy, that must have taken some time to type 

Did you get your lab tests done privately, or was that through your medical provider?

[Tychy]

You bet, I was late at work xD

This was done through my medical provider as part of the exclusion protocol. I'm basically tired all the time and hypogonadism was one of the possible explanations, so I got looked at by an endocrinologist. Things still in the pipeline are cardiac valvular defect (unlikely) and EDS (yay, got my referral today...waiting time like 2 months or so?).

Did a quick glucose test: 108 after coffee with milk on empty stomach, 98 two hours after lunch. I think that's fairly normal. I'd start to worry around 125 and panic at 140.

What's happening in EDS is actually that the baroreceptor is malfunctioning, so the body does not counter low blood volume and will not properly constrict the blood vessels in your legs when standing. So blood pools in your legs. It will then increase heart rate to supply enough oxygen to the brain, by pushing out stress hormones that can lead to panic attacks. In worst case you have a syncope. Also your kidneys will just drop fluid and salt out of your system, because "everything is fine", leading to dehydration.
I don't have hunger and thirst. Thirst is the baroreceptor. I think there is something similar in the stomach for hunger.

Time will tell. Maybe it's just a genetic dysautonomia. Treatment would be a seven-days-a-week excercise protocol, which I'm actually fine with by now...

[Paolo]

Thanks Tychy, I myself have had episodes of PAD (Peripheral Artery Disease) that admittedly I self diagnosed but haven't had symptoms (pain walking that is progressive) for more than 18 months  , think diet and supplements have helped with that  . I used to indoor row a lot, bizarrely exercise seemed to make PAD worse in my case.

If the PAD comes back then I am definitely going to try Pentox as I believe it specifically helps with PAD.

Blood pooling in you legs sounds bad, hope you find a treatment for it, take care 

[Tychy]

Huh, be sure to get that checked out at some point. PAD and arteriosclerosis are no fun, if blood vessels in your brain are become involved.

Blood pooling in legs and hands is not that bad. I'm used to it. It feels pressury. No black legs or something like that

[Tychy]

I'll leave this study here, as it's revelant to the topic
https://link.springer.com/article/10.1007%2Fs00394-016-1199-8
(Probiotics and insulin)

[skunkworks]

Conclusion

Probiotics modestly improved HbA1c and fasting insulin in people with type 2 diabetes.

[Paolo]

I take probiotics and have done so for some months, so guess that's a good thing in this respect 

Although I am not diabetic its all good 

[skunkworks]

Sorry for not providing that study. It is interesting that tgf-beta gets attention and not myostatin, which IS part of the tgf-beta family, and is clearly linked to fibrosis and other issues.

https://www.youtube.com/watch?v=o6A9bbDI6fo

Human Myostatin Knock-Out Targeting CRISPR-Cas9 Plasmid - The ODIN

[NeoV]

Big update here.

The main gene thought to be responsible for Peyronie's, and Dupuytren's has been cited to be HLA-B7. This is activated by histone deacetylase. Activation of the same gene causes an increased risk of cancer, and this was referenced in October 2017 in the report on Peryonie's sufferers at an increased risk of cancer due to genetic etiology.

Guess what is a massive deactivator of hystone deacetylase and this gene is? A ketogenic, or LOW carb, fasking like diet, which has reversed all my nerve pain, penile numbness, and made my Peyronie's the best it's been yet. As I have mentioned, my father has completely numb feet, a numb penis, and calcified Peyronie's disease. The fact that I have reversed my penile numbness and my neuropathy is a huge deal to me.

Histone deacetylase, a new target for Peyronie's
Histone deacetylase inhibition: a new target for Peyronie's disease? - Cellek - 2014 - BJU International - Wiley Online Library

Histone deacetylase: a potential therapeutic target for fibrotic disorders.
https://www.ncbi.nlm.nih.gov/pubmed/20719940

Ketogenic diet inhibits histone deacetylase
http://www.cell.com/endocrinology-metabolism/abstract/S1043-2760(13)00156-2
https://www.ncbi.nlm.nih.gov/pubmed/29024787

"Inhibition of HDACs can repress TGF-bemediated signaling...
They observed a 60% decrease in HDAC2 expression in Peyronies Disease plaque derived
fibroblasts transfected with the HDAC2-targeted siRNA"
From: http://www.smr.jsexmed.org/article/S2050-0521(15)00003-7/pdf

Low carb and ketogenic diets are now being used to treat and reverse alzheimer's symptoms, parkinsons, diabetes type 2 AND 1 even, heart disease, as adjunct cancer therapy, and in many other diseases. A ketogenic or low carb diet does not need to be animal based, it can be done on a plant based diet as well.

[Tychy]

Thanks, wow. That stuff is from 2014
https://www.ncbi.nlm.nih.gov/pubmed/24841412

RESULTS:
We observed that Ad-HDAC2 shRNA decreased inflammatory cell infiltration, reduced transnuclear expression of phospho-Smad3 and regressed fibrotic plaque of the tunica albuginea in Peyronies Disease rats in vivo. siRNA-mediated silencing of HDAC2 significantly decreased the TGF-β1-induced transdifferentiation of fibroblasts into myofibroblasts and collagen production, and induced apoptosis by downregulating the expression of PARP1, and decreased the expression of cyclin D1 (a positive cell-cycle regulator) in primary cultured fibroblasts derived from human Peyronies Disease plaque in vitro.

Remember that rodent studies have like a 90% failure rate in transferring to humans, still this sounds good! Recently started LCHF diet again to counter weight gain, I think I'll keep at it ;P

[Crooked_Stick]

Wow great post NeoV....it looks like niacin is an inhibitor (Class III HDACs (sirtuins) are dependent on NAD+ and are therefore inhibited by nicotinamide as well as derivatives of NAD, dihydrocoumarin, napthopyranone and 2-hydroxynaphaldehydes [5].)

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4210916/

[Paolo]

Great work Neo 

For those interested or perhaps not below is an article on Butyrate, I found it very interesting;

https://www.selfhacked.com/blog/butyrate-health-benefits-butyrate-derivatives-sodium-butyrate-phenylbutyrate-trybutyrine-butyric-acid-butyrate-prodrugs-butyrate-producing-bacteria/#Butyrate

Paul (paolo) 

[Tychy]

Niacin may actually increase diabetes risk, nicotinamide is safe for up to 3g/day: https://link.springer.com/article/10.1007%2Fs001250051536

Note that nicotinamide is used in the methylation cycle and uses up methyl groups. If you have a problem with undermethylation, supply methylcobalamin (methyl-B12).

Edit: interesting! While an overload on these is bad, the following supplements / foods inhibit HDACs: Curcumin, Quercetin, Garlic, Onions, cruciferous vegetables (Broccoli sprouts, cabbage, Brussels sprouts, cauliflower, and kale), Resveratrol, EGCG (green tea).

All of these showed up on my radar in the past. That explains a lot.

[NeoV]

My mistake, I corrected my original and recent post.

The gene is HLA-B7, which is activated via methylization, by histone deacetylase (HDAC). Insulin resistance causes an increase in HDAC, while the ketone body beta hydroxybutyrate (produced by the ketogenic diet or fasting), reduces it. Keep your diet low insulin if anything, and consider a cup of coffee + grass fed butter : )

[Paolo]

That's good, coffee and butter (grass-fed) = bulletproof coffee 
I already use  for months coffee and MCT oil (C8) so I think that's a good thing to do.

BHB (beta-hydroxybutyrate) is chemical the liver produces when going into ketosis. It not only acts as a signalling molecule for the body that fat is to be the primary fuel source, but acts as precursor for ketones. Amongst other things, it is the BHB molecule that signals to lower blood glucose, and the presence of BHB is thought to benefit the body in a number of ways, even if the body is not truly in ketosis. Think of BHB as a signalling molecule first, and an energy source second.
MCTs on the other hand are simply a good energy source. They can pass straight into the mitochondria and get converted into ketones for energy. The presence of MCT and the ketones it is broken down into will undoubtedly do some signalling too, and can stimulate natural production of BHB in the liver. Think of MCT as an energy source first, and a signalling molecule second.

BHB + MCT = Good 

MCT Studies:- https://www.ncbi.nlm.nih.gov/pubmed/7072620
https://www.ncbi.nlm.nih.gov/pubmed/18296368
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4882694/

[NeoV]

I love bulletproof coffee! But I have yet to try it with MCT oil. I have been on a ketogenic diet or close to ketogenic for over six months (probably a lot longer!), and I have loved what it has done for my strange health issues and penis. You're right, even fasting or simply skipping breakfast and having some fat can produce BHB. Checking out that article now.

[Tychy]

I use MCT oil every morning in my protein shake. So far that's keeping me from snacking until lunch

I took 50mg of nicotinamide / niacinamide yesterday (still had a bottle on the shelf) and was greeted by instant dizzyness and stomach upset. Today I have severe anxiolytic effects, like from benzos, and diarrhea. May not be for everyone xD Keeping to broccoli sprouts...

PS: Body does convert tryptophane to niacinamide, if there is not enough in the system. I may have experienced a second hand tryptophane -> serotonine rush.

[NeoV]

Some studies on how insulin directly raises TGF-beta and TGF-beta receptors, plus ROS, all CAUSES of peyronie's.

Insulin directly increases tgf-beta, ROS,
https://www.hindawi.com/journals/ijmg/2014/180270/

Insulin directly increases tgf-beta and fibrosis
https://www.ncbi.nlm.nih.gov/pubmed/26420907

Tgf-beta status of prediabetic americans
http://www.kidney-international.org/article/S0085-2538(15)54527-4/pdf

I made a new YouTube video on this topic. Treat insulin as ENEMY #1 when it comes to ALL diseases of modernity. This is no joke, the research is starting to blow up on how serious hyperinsulinemia (silent pre-diabetes) causes many diseases included all-organ fibrosis.

[Paolo]

NeoV, Linked below is a study on inhibition of HDAC7 (may represent a promising epigenetic therapy for Peyronies Disease).
epigenetic = relating to or arising from non-genetic influences on gene expression.

https://www.ncbi.nlm.nih.gov/pubmed/29706035

Thoughts??
Paul (paolo) 

[NeoV]

Oh my god.. so they have been watching my thread and our forums LOL.

Well, keep off the carbs, try fasting, and keto : )

[Crooked_Stick]

NeoV.....can you give us the link between keto and HDAC inhibition? Also Sulforaphane (from broccoli) is an HDAC inhibitor.....

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2777483/

[skunkworks]

Great finds Paolo and Crooked_Stick!

[pey ron]

which sulphoraphane supplements give the best bang for the buck?

[Paolo]

If you Google Avmacol Nutramax you should find what you are looking for, seems to have good reviews 

Advantage is it bundles the enzyme myrosinase alongside its glucoraphanin.

If any benefit after a month then please report back 
Paul

[pey ron]

From the SelfHacked secrets e-book:

«Hi­-maize resistant starch results in butyrate production»

Also, I see there are Sodium Butyrate supplements. Are those related? Would they help?

[NeoV]

No reason to take a supplement. Eat fat and fast, and your liver will pick up lipids in your blood and turn them into beta-hydroxybutarate. This inhibits histone deacetylase.

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3735349/

[pey ron]

Eat fat and fast

I know the theory but it's not easy to follow given my extremely hectic lifestyle. Maize seems like it will stimulate BHB production even if i don't cut carbs from my diet. Can someone confirm?

[TonySa]

Doubtful it disbetics would be using it, although I’m not sure

[pey ron]

«Rho-Kinase Inhibition Ameliorates Metabolic Disorders through Activation of AMPK Pathway in Mice»
Rho-Kinase Inhibition Ameliorates Metabolic Disorders through Activation of AMPK Pathway in Mice

is it relevant to this thread?

Reason why I ask is that I just found this new article from the awesome Marcus M Ilg that already presented those posters on high throughput screening of drugs for Peyronie:

«RhoA kinase-inhibition prevents myofibroblast transformation in a cell culture model of Peyronie’s disease»
[email protected] - DocDroid

[Paolo]

Maize seems like it will stimulate BHB production even if i don't cut carbs from my diet. Can someone confirm?

Yep, I agree, it is somewhat of a cheat if you will rather than going very low carb
Paul 

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