Low-Carbohydrate diets & metabolic response to ADT

[pjoshea13]

A new study from Steve Freedland [1].

"... {Low-Carbohydrate Diet} intervention significantly reversed many ADT-induced metabolic changes while slightly enhancing androgen reduction."

-Patrick

[1] pubmed.ncbi.nlm.nih.gov/339...

Prostate

. 2021 May 5. doi: 10.1002/pros.24136. Online ahead of print.

The influence of low-carbohydrate diets on the metabolic response to androgen-deprivation therapy in prostate cancer

Jen-Tsan Chi 1 , Pao-Hwa Lin 2 , Vladimir Tolstikov 3 , Taofik Oyekunle 4 , Gloria C G Alvarado 5 , Adela Ramirez-Torres 5 , Emily Y Chen 3 , Valerie Bussberg 3 , Bo Chi 1 , Bennett Greenwood 3 , Rangaprasad Sarangarajan 3 , Niven R Narain 3 , Michael A Kiebish 3 , Stephen J Freedland 5 6

Affiliations collapse

Affiliations

1 Department of Molecular Genetics and Microbiology, Center for Genomics and Computational Biology, Duke University Medical Center, Durham, North Carolina, USA.

2 Division of Nephrology, Department of Medicine, Duke University Medical Center, Durham, North Carolina, USA.

3 BERG, Framingham, Massachusetts, USA.

4 Duke Cancer Institute, Duke University Medical Center, Durham, North Carolina, USA.

5 Center for Integrated Research in Cancer and Lifestyle, Cedars-Sinai, Los Angeles, California, USA.

6 Durham VA Medical Center, Durham, North Carolina, USA.

PMID: 33949711 DOI: 10.1002/pros.24136

Abstract

Background: Prostate cancer (PC) is the second most lethal cancer for men. For metastatic PC, standard first-line treatment is androgen deprivation therapy (ADT). While effective, ADT has many metabolic side effects. Previously, we found in serum metabolome analysis that ADT reduced androsterone sulfate, 3-hydroxybutyric acid, acyl-carnitines but increased serum glucose. Since ADT reduced ketogenesis, we speculate that low-carbohydrate diets (LCD) may reverse many ADT-induced metabolic abnormalities in animals and humans.

Methods: In a multicenter trial of patients with PC initiating ADT randomized to no diet change (control) or LCD, we previously showed that LCD intervention led to significant weight loss, reduced fat mass, improved insulin resistance, and lipid profiles. To determine whether and how LCD affects ADT-induced metabolic changes, we analyzed serum metabolites after 3-, and 6-months of ADT on LCD versus control.

Results: We found androsterone sulfate was most consistently reduced by ADT and was slightly further reduced in the LCD arm. Contrastingly, LCD intervention increased 3-hydroxybutyric acid and various acyl-carnitines, counteracting their reduction during ADT. LCD also reversed the ADT-reduced lactic acid, alanine, and S-adenosyl methionine (SAM), elevating glycolysis metabolites and alanine. While the degree of androsterone reduction by ADT was strongly correlated with glucose and indole-3-carboxaldehyde, LCD disrupted such correlations.

Conclusions: Together, LCD intervention significantly reversed many ADT-induced metabolic changes while slightly enhancing androgen reduction. Future research is needed to confirm these findings and determine whether LCD can mitigate ADT-linked comorbidities and possibly delaying disease progression by further lowering androgens.

Keywords: 3-formyl indole; 3-hydroxybutyric acid; ADT; androgen sulfate; indole-3-carboxaldehyde; ketogenesis; low carbohydrate diet; metabolomics; prostate cancer.

© 2021 Wiley Periodicals LLC.

[Hidden]

Now if we could just figure out how to prevent the muscle wasting on ADT....

[GeorgeGlass in reply to Hidden]

I've observed that my lower body muscles are not disappearing, while using Orgovyx, at a rate that they did when I took Lupron. Taken Lupron would get me to about 181 lbs within a couple months. I've been on Orgovyx for a couple months and I'm around 188, close to when I started taking it.

[Hidden in reply to GeorgeGlass]

Good to know. Orgovyx decreases testosterone faster than Lupron and your testosterone should recover faster after ending ADT.

[GeorgeGlass in reply to Hidden]

True. I’m sure I’ll ever got off it though. We’ll see

[Boywonder56]

Guess i better put the french fries down...good reporting pj

[Hidden]

You're kind of doing Keto then.I've done half a dozen keto cycles since being diagnosed. I'm not certain what that is doing, if anything, to the prostate cancer. But might not hurt since advanced prostate cancer is more glucose-driven. I don't want to lose weight but it rips off 10-20 lbs in just a week or two (and when I go off I gain 10+ lbs the first day!). Almost all water - 2.5 grams per gram of glycogen.

[FinalBossMatt in reply to Hidden]

Mentally and emotionally, a Keto diet or just high fats, in general, keep your hormones balanced and keep you in a good mental state. That what happened to me when I was first diagnosed. If I wasn't careful about my fat and carb intake, I would get into a world of depression until eventually, my body adjusted.

It blew me away how people told me I needed to be on a plant-only diet because I would have been in the fetal position on the ground crying thinking the world was going to come to an end crying my eyes out.

It actually healed up my bones from the mets damage too since I was eating food with a lot of calcium in it. That's a fat-soluble vitamin so the saturated fats helped shuttle that stuff to the correct location.

[Hidden in reply to FinalBossMatt]

Estrogen patches eliminate depression and bone loss. The eliminate cardio risk after the first year.

But we don't know a way around the other effects of zero T. Libido and muscle loss. Those ones destroyed me mentally. Plus the chance of gyno is a lot higher than when one does Lupron. I had to get nipple covets. Salt in the wound.

I don't think I ever tried keto while on the patches though. Good to know.

[CSHobie in reply to Hidden]

Based on your recomendation, I asked my one MO for patches, he declined. I am going to ask my other MO today, I hope it is as good as you found it to be, for me too.

[Hidden in reply to CSHobie]

Best of luck. Print out the PATCH trial. It might help your cause. I self directed because it was 2 years ago.

[CSHobie in reply to Hidden]

Thanks, I just spoke to him, he says he has never given anybody the Patch, he has seen no evidence of any benefit. He suggests Effexor. Being a Government health system, they have no ability to look at anything that is not SOC. We can replace these expensive Drs with a flow chart computer program.

[Hidden in reply to CSHobie]

I understand. Patches aren't SOC yet. They haven't been approved as of today.

For what it's worth, I did estrogen patches two years ago and I think it cost me about $140 a month (no insurance other than goodrx.com).

physiciansweekly.com/patch-...

[Hidden in reply to CSHobie]

I like that idea. Perhaps reduce doctors by 75%. I think they are still valuable for consultation but shouldn't be an automatic first choice. Particularly when some of them play "God" and think that they know what is better for you than you do (they are paid consultants but for some reason, it's gone awry).

[noahware in reply to CSHobie]

If he has seen no evidence of any benefit of E2 patches, it is because he is not looking. A google search will reveal many papers (not just PATCH trial) suggesting very strong evidence that E2 patches help reduce hot flashes and bone loss, among other benefits.

Like many docs, his view of "evidence" appears self-referential: because HE doesn't do it, he sees no evidence of benefit. Well, of course!

My daughter just graduated med school, and agrees that it is basically a trade school. You learn to do what everyone else does, and ply your trade, but NOT to keep looking at new science and go forward wherever it takes you (as that would set you up for potential litigation).

[MateoBeach in reply to CSHobie]

I agree with looking to switch to another MO under these circumstances. My first MO said he would not recommend anything "outside the guidelines" (=SOC). I told him that I did not need him for that as I could, and have, read the guidelines for myself. I needed him to be a check and sounding board for what I wanted to add to SOC. We got along well after that. But now I have a much more open-minded and science driven MO. Better.In addition to providing your doctors with the best and most relevant peer-reviewed articles on whatever topic-of-interest. (Such as the PATCH trial and others in this case). You might start slow and ask for low dose estradiol patch (0.10mg/day changed every 2 days, for example) in addition to regular ADT, rather than in place of it. And emphasize that there has been no increase in adverse cardiovascular events with topical estradiol in clinical trials (unlike oral DES). Good luck. And persist.

[GeorgeGlass in reply to MateoBeach]

Mateo, what do you think about S-Adenosyl-Methionine SAMe supplements? Some guys on here take SAMe supplements. I noticed they are mentioned in this post. Do they help suppress the cancer?

[Karmaji in reply to CSHobie]

I had the same problem...My Onco wont prescribe.Then I took a different path to handle hot flashes which drove me crazy.

And it worked and hot flashes are reduced by 80 % and of very low intensity....

No body will do RCT on this....

Acupressure on about 10 points... takes 5 minutes twice a day...even when walking by

pressing some parts...Reduced by 50 %

Then added essential oil cum vegetable oil as massage....

Now have only 20 % Hot flashes....very mild

Simple living...no chemical drugs

Very healthy therapy....at no cost....

[GoBucks in reply to Karmaji]

Karmaji, where are those 10 points for accupressure?

[Karmaji in reply to GoBucks]

Best is google on acupressure for menopause

and essential oils for hot flashes...Oils just for rubbing ..no intake

yogajournal.com/lifestyle/h...

and I found the book very simple and clear...

Acupressure Made Simple: Easily Treat Yourself for Common Ailments

Bleecker, Deborah

For such therapies...one has to believe it may work and enjoy doing pressure points....

and it is free for all , away from toxic drugs and big pharma

Sure nothing against scorched. earth toxic therapies when stuck...a part of life

One may use some veg oil...Nigel .....essential oils...

For me acupressure reduced by half...

Then I used essential oils cum carrier oil... Nigel etc

Clary sage

Fennel .

Geranium peppermint

Neroli

Lavender

=======

For me about 50 % reduction thru acupressure 2 or 3 times a day...even when walking I hold my hands around wrist at pressure points

Essential oil rub on lower belly reduces further...

The two therapies reduced by 80 % and with less intensity....

All these things work or may not work as each human being has different mind body states..... and these things are not toxic...

=======

And on a mental level...

I tell my Self I am not the body...

I look at my body as an object to observe in a relaxed mood

I become you ... looking at my state

May bring some calmness and smile

========

As Dr Scholz says ..;try any supplement ...

If works ....OK

otherwise ...do not take or do

Need no clinical studies....

I am the study...who is better than my own unconditioned Self to know my own conditioned mind body unless I am a connected object...

[GoBucks in reply to Karmaji]

Thanks much.

[MateoBeach in reply to Karmaji]

👍👍👍 I See my Self in you, Karmaji. Thank you for your presence here.

[Karmaji in reply to FinalBossMatt]

PC is very heterogeneous. People react in different ways to treatments....Our body has different signatures..even if we all have APC....

Like in my case, 81 years, I had no strong reaction to ADT....since 2 years.

No bone loss, no muscle loss, no depression....

Loss of Libido is activated thru mental libido pathways....if one wishes

No sexual desire whatsoever...on physical level

.Then I activate my old memory when sex was so motivating and fulfilling...It seems thru mental pathways...I create Libido ....

We are all different even if we are all human beings.....It is mind body game....

What shall be shall be......

who cares...

we shall all shed our physical robe.....

Till then live every moment fully joyfully a mind game....

[dhccpa]

Is that the diet you follow? The Keto diet more or less?

[Stoneartist]

I totally agree with NAL. I keep to about 30gm carbohydrates/day and I am doing well with PCa. Using only Zolatex 3 monthly injections and no other meds or supplements. I think this is the best way to help the body get on with its own repair work. PSA down to 1.5 (from 1000 15 months ago) metastases in bone and lymph showing reduction with regeneration of healthy tissue. It doesnt even feel like a diet - just an alternative approach to food -

Martin

[CSHobie]

Back to the topic, check out this biodiet.org/articles-and-st...

The book basically shows how our American High Carb low fat diet is not making us healthier.

Basically the Keto diet is the way to go, no doubt that there are benefits. Once PCa becomes Hormone insensitive, Keto is a good way to eat, because C$%*&R can't live on Ketones

[Karmaji]

Interesting link of LCD and ADT.....means glucose metabolic pathways ??

[j-o-h-n]

To the Rush Limbaugh of H.U. a belated birthday wish to you with many healthy ones to come...

Good Luck, Good Health and Good Humor.

j-o-h-n Friday 05/07/2021 5:15 PM DST

[Hidden]

I find the depression crushing. Only been 8 months but I’m still struggling for a routine and mental stability. I know the need to exercise but it’s hard to get to even that small accomplishment. Every day adjust further to my new life but negativity and anger still creep in.

[noahware in reply to Hidden]

Ask a doc about low-dose estrogen patches... it is known to help with hot flashes and bone loss, but for some men it also helps with brain fog and depression.

[jmurgia in reply to Hidden]

Mr. Saville I agree 100% with your observations. Is it as dark and dreary in Rochester these days as it is in Syracuse? I've been at this for 19 years. Didn't seem to bother me when I was working up and down 81 and the Thruway, but now that I'm home all the time the lack of sunshine is crushing. Joe

[Pheart2]

Hi Patrick, in that study of Law Carb diet how much gram of Carb/day was allowed. Thank you.

[pjoshea13 in reply to Pheart2]

I can't get to the full text, but from an earlier Freedland paper:

"The LCD arm was instructed by a dietitian to limit carbohydrate intake to ≤20

grams/day."

-Patrick

[Pheart2]

Thx. Appreciated.

[GoBucks]

I started a very carb conscious "diet" and lost weight. But then I went back to old ways. After I have the last cupcake with coffee tomorrow I am going back to focusing on lowering my daily intake.

[CSHobie in reply to GoBucks]

That is funny, me too. I rediscovered my love for donuts, suddenly. lol

[GoBucks in reply to CSHobie]

I toughened up this morning. Did NOT eat the cupcake. I'm on my way.

[MateoBeach]

Thanks for posting this Patrick and sparking the great discussion. Wish I had the full article to dig deeper. The response of increasing acyl-carnitines by LCD is interesting. I was previously supplementing acyl-L-carnitine for mitochondrial support but have since dropped it.I too am a ketogenic eater and OMAD intermittent faste, and enthusiastic advocate, for the past 18 months. So nice to see so many like-minded advocates here, among our plant-based only bretheren. Keto does require some re-education and adaptation at the outset. Worth it!

The problem that persists, even when very lean and full of energy from keto, is the muscle wasting (sarcopenia) from hypogonadal state, that also reduces the response to resistance exercise in muscle rebuilding and maintenance.

That is why I am undertaking cyclic trials of high testosterone. Will report on this further in due time.

[GeorgeGlass]

Patrick?

Do these studies ever include two-carb groups, so they can compare the junk food carbs against organic steel cut, slow-cooked oatmeal with organic fruits (both in moderation) along with healthy fats like (avocados nuts etc) and plenty of veggies and greens? Obviously, the former is bad for anyone but maybe the latter is very good, even if the carbs go between 75-100 per day, due to the fact that the oatmeal and fruit have a glucose lowering effect (the opposite of the junk carbs).

Also, what do you think about S-Adenosyl-Methionine SAMe supplements? Some guys on here take SAMe supplements. I noticed they are mentioned in this post. Do they help suppress the cancer?