Fibroblast Growth Factor 23

[pjoshea13]

New paper below [1].

Over the years, Mark McCarty has written some thoughtful papers on PCa, i.e. from the perspective of someone interested in the effect of dietary factors. Here, he gives advice on dealing with a PCa growth factor that has had little attention.

"Fibroblast growth factor 23 (FGF23), a hormonal regulator of phosphate and vitamin D metabolism produced primarily in bone by osteocytes and mature osteoblasts, is now known to have growth factor activity for many prostate cancers. In some of these cancers, autocrine production of FGF23 drives their proliferation. FGF23 synthesized within bone likely promotes the expansion of prostate cancer bone metastases."

We already know that excess calcium & phosphate is associated with aggressive PCa, & maybe FGF23 is the connection:

"... dietary or lifestyle factors which boost bone's production of FGF23 may encourage the ... spread of prostate cancer."

"High dietary intakes of bioavailable phosphorus and of calcium have been found to boost FGF23 levels, and this accords well with prospective epidemiology pointing to high intakes of both phosphate and calcium as risk factors for aggressive prostate cancer."

I have never been enthusiatic about a vegan diet for PCa, in that I have never seen a case made for a particular form. "Vegan" is supposed to be self-explanatory. But cancer cells like good nourishment too.

The intrigueing thing about a vegan diet is that is that it is close to insufficiency for some nutrients, & can be easily manipulated to be restrictive for, say, an essential amino acid. Perhaps someone will one day come up with a vegan diet tailored for PCa.

McCarty suggests eating a "plant-based diet relatively low in bioavailable phosphate and calcium".

My (omnivore) approach has been:

- avoid deli meats with phosphates

- ditto soft drinks

- limit portion size for fish & meat, because of phosphorus content

- avoid dairy

- do not use calcium supplements

Note that both are vital nutrients & cannot be eliminated entirely from the diet.

For more on FGF23, see [2]. It is a full-text link.

-Patrick

[1] ncbi.nlm.nih.gov/pubmed/281...

Med Hypotheses. 2017 Feb;99:68-72. doi: 10.1016/j.mehy.2017.01.001. Epub 2017 Jan 3.

Plant-based diets relatively low in bioavailable phosphate and calcium may aid prevention and control of prostate cancer by lessening production of fibroblast growth factor 23.

McCarty MF1.

Author information

Abstract

Fibroblast growth factor 23 (FGF23), a hormonal regulator of phosphate and vitamin D metabolism produced primarily in bone by osteocytes and mature osteoblasts, is now known to have growth factor activity for many prostate cancers. In some of these cancers, autocrine production of FGF23 drives their proliferation. FGF23 synthesized within bone likely promotes the expansion of prostate cancer bone metastases. Hence, dietary or lifestyle factors which boost bone's production of FGF23 may encourage the induction and spread of prostate cancer. High dietary intakes of bioavailable phosphorus and of calcium have been found to boost FGF23 levels, and this accords well with prospective epidemiology pointing to high intakes of both phosphate and calcium as risk factors for aggressive prostate cancer. Hence, prospective studies correlating baseline FGF23 levels with subsequent risk for prostate cancer, or advanced prostate cancer, are needed. Natural plant-based diets, though not inherently low in calcium or phosphorus, provide forms of these that are less bioavailable than those in animal products, and hence may be expected to down-regulate bone's production of FGF23. This may play a role in the lower risk for clinical prostate cancer observed in vegans and quasi-vegan cultures. Other factors, such as decreased IGF-I levels and mTORC1 activity, may also play a role in this regard.

Copyright © 2017 Elsevier Ltd. All rights reserved.

KEYWORDS:

Calcium; FGF23; Phosphate; Plant-based diet; Prostate cancer; Vegan

PMID: 28110703 DOI: 10.1016/j.mehy.2017.01.001

[PubMed - in process]

[2] ncbi.nlm.nih.gov/pmc/articl...

Oncotarget. 2015 Jul 10;6(19):17291-301.

FGF23 promotes prostate cancer progression.

Feng S1, Wang J1, Zhang Y2, Creighton CJ2,3, Ittmann M1.

Author information

1Department of Pathology and Immunology, Baylor College of Medicine and Michael E. DeBakey Dept. of Veterans Affairs Medical Center, Houston, Texas, USA.

2Dan L. Duncan Cancer Center Division of Biostatistics, Baylor College of Medicine, Houston, Texas, USA.

3Department of Medicine, Baylor College of Medicine, Houston, Texas, USA.

Abstract

Prostate cancer is the most common cancer in US men and the second leading cause of cancer deaths. Fibroblast growth factor 23 (FGF23) is an endocrine FGF, normally expressed by osteocytes, which plays a critical role in phosphate homeostasis via a feedback loop involving the kidney and vitamin D. We now show that FGF23 is expressed as an autocrine growth factor in all prostate cancer cell lines tested and is present at increased levels in prostate cancer tissues. Exogenous FGF23 enhances proliferation, invasion and anchorage independent growth in vitro while FGF23 knockdown in prostate cancer cell lines decreases these phenotypes. FGF23 knockdown also decreases tumor growth in vivo. Given that classical FGFs and FGF19 are also increased in prostate cancer, we analyzed expression microarrays hybridized with RNAs from of LNCaP cells stimulated with FGF2, FGF19 or FGF23. The different FGF ligands induce overlapping as well as unique patterns of gene expression changes and thus are not redundant. We identified multiple genes whose expression is altered by FGF23 that are associated with prostate cancer initiation and progression. Thus FGF23 can potentially also act as an autocrine, paracrine and/or endocrine growth factor in prostate cancer that can promote prostate cancer progression.

KEYWORDS:

FGF23; endocrine fibroblast growth factors; fibroblast growth factors; prostate cancer; signal transduction

PMID: 26019137 PMCID: PMC4627308 DOI: 10.18632/oncotarget.4174

[PubMed - indexed for MEDLINE] Free PMC Article

[Neal-Snyder]

Thanks, Patrick. Is there any information you use to guide you in selecting fish & meat (non-deli) to minimize phosphorus content, or is it all just a matter of eating small portions? For instance, does shellfish have a relatively high phosphorus content? Does wild-caught fish have less than farmed? Do some fish have less than others? Does the high praise for wild-caught Alaskan salmon have anything to do with low phosphorus content? Thank you very much for your attention to & consideration of these questions.

Neal

[pjoshea13 in reply to Neal-Snyder]

Neal,

The USDA Database is useful here [1].

Cuts of meat vary, depending on the percentage of protein.

Note that 100g = 3.5oz.

mg/100g:

- beef chuck = 214

- lamb = 156

- pork loin = 247

- cod = 203

- shrimp = 214

- haddock = 227

- scallops = 334 !!!

RDA = 700 mg. [2]

I'd stay clear of the 24 oz T-bone at Ruth's Chris.

On the very rare occasion that I want a burger, I make it with 6oz meat. You can't make an outstanding burger with less. But that's twice the protein that I need. Once a year is not a problem, but I otherwise stick to 3-4oz portions of protein for the main meal of the day.

-Patrick

[1] ndb.nal.usda.gov/ndb/

[2] lpi.oregonstate.edu/mic/min...

[Neal-Snyder in reply to pjoshea13]

Thanks, Patrick--that's very helpful. Two smaller questions: Do you allow yourself any animal protein at another meal in the same day, or does that depend on the mg's of phosphorus in your main meal? Do you eat any soy protein?

Thanks, Neal

[pjoshea13 in reply to Neal-Snyder]

Neal,

No soy protein.

I tend to eat only two meals. A small amount of protein at breakfast, & not a lot at night. Probably consistent with Barry Sears "Zone" proportions. Was interested to hear Myers mention him. Sears tells you how to calculate protein needs. It's worth reading. Pointless to eat excess protein.

-Patrick

[Hidden in reply to pjoshea13]

I replaced the milk in my cereal with soy milk so I get soy protein. I heard that soy is good for moderating hot flashes. I think the soy milk also brags about having more calcium than milk. If we are at risk for osteoporosis due to ADT, don't we need calcium?

[Neal-Snyder in reply to pjoshea13]

Thank you, Patrick. I do the 2-meal thing a lot, plus a snack of multiple kinds of fruit, with walnuts & seeds. (I'm up to a handful of walnuts without digestive problems.) I've been eating my oatmeal with 100% soy milk, & I just switched to 100% almond milk--no calcium, etc.

Do you have any trouble keeping your weight up? I'm down 20 pounds (over the years I've been fighting PCa) that I didn't need to lose, & now I'm going to eat less protein ...

Neal

[pjoshea13 in reply to Neal-Snyder]

Less protein doesn't mean you should lower total calories. -P

[Neal-Snyder in reply to pjoshea13]

OK, I'm eating tons of (usually organic) fruits (including avocados) & veggies. I eat a very large bowl of oatmeal, with fruits, brown rice, coconut oil & almond milk, for breakfast daily. I've been eating fish/shellfish at my one or two other meals. I eat beans, lentils, grains (especially brown rice & quinoa), sweet potatoes & potatoes. I have nuts, seeds & raisins daily. Recently, after reading what you eat, I'm eating some pork. A large portion of what I eat is smothered with delicious Asian, usually spicy, hopefully not too sugary, sauces. I eat dishes that include cooked tomato.

What I haven't been eating is "white": breads, bagels (I used to eat 2 per day), tortillas, nan, white rice, waffles, pancakes, let alone desserts. I haven't been eating sweets. My wife is "threatening" to make French toast for me here in Chiang Mai, with some good bread, wonderful eggs, & good fake maple syrup. I think she will & I'll eat it. Seconds too.

I have a very healthy appetite. My wife says almost nothing I generally eat anymore will put any weight on me. I went from my adult weight of 165 to my high school weight of 155 to my junior high weight of 145.

A nutritionist who spoke at a cancer center said potatoes are neither good nor bad for cancer patients. But they need to be eaten with restraint, don't they?

Any ideas you have about how I can make my diet more fattening without being more inviting to PCa cells will be most appreciated, from the bottom of my stomach! Thank you, Patrick.

Neal

[pjoshea13 in reply to Neal-Snyder]

Neal,

I'm not seeing a lot of fat in that list. I suppose that the nuts can contribute a fair amount though.

I think you should try Barry Sears Zone diet for a month. Each meal has to be balanced in terms of the carb:fat:protein ratio. t's easy after a while:

"40% Carbs : 30% Protein : 30% Fat"

But the key is calculating the number of "blocks" to consume each day. Here is an online calculator:

dbhonline.com/zoneful/p_cal...

Biblio.com has used Zone books for peanuts:

biblio.com/search.php?autho...

-Patrck

[Neal-Snyder in reply to pjoshea13]

Thank you very much, Patrick! We won't be back from Southeast Asia until March 20, but I can have a book waiting for us. In the meantime, I'll put Yvonne to work trying to figure out how to get started while we're here. She knows food far better than I, & she's the one who'd like to see more meat back on my bones!

Cheers,

Neal

[Neal-Snyder in reply to Neal-Snyder]

Patrick, it's Yvonne's understanding that fat doesn't fatten you, carbs do. Is that your understanding or not?

Thanks, Neal

[pjoshea13 in reply to Neal-Snyder]

Neal,

How are cows fattened-up on feed lost? With soy & corn.

On a high-carb diet (low fat), the glucose spikes force a conversion of excess glucose to triglycerides & fat storage.

With a high fat diet, we don't create a glucose crisis.

-Patrick

[Neal-Snyder in reply to pjoshea13]

Patrick,

Thanks for the explanation! Time to go into 40-30-30 crisis mode. No corn or soy for me, though. I also read some advice online for healthy weight gain.

Neal

[Hidden in reply to pjoshea13]

Patrick,

Can we share the steak? For those who don't know, Ruth's Chris is a red meat paradise, cooked to perfection. Pricey, but every bite worth it.

Joe

[gottodealwithit]

So where does this information leave someone who is on ADT. One of the risks of chemical castration and subsequent lack of Testosterone is loss of bone density. Thus my oncologist recommended Calcium supplementation and D3. I also take K2 to ensure the calcium is going to bone not to linings of blood vessels.

[Hidden in reply to gottodealwithit]

Hi Gotto,

While my Onc was on vaca, I saw one of his partners. He asked if I was taking a Calcium/D-3 supplement. I said no, he said start, and they sit here unopened. I will look into this some more, but I think what happens is the Calcium interferes with the action of drugs like Xofigo and Xgeva. I imagine any drug that specifically targets bone mets, may be interfered with by taking the supplement. I do know that the body recognizes Xgeva as Calcium, and thus it is attracted to the met. So, taking a Calcium supplement may be overkill for the system to handle.

Joe

[gottodealwithit in reply to Hidden]

I am halfway through a 2 year Lupron regime, injection every 6 months. I have read the book Vitamin K2 and the Calcium Paradox by Kate Rheaume-Bleue. She argues with supporting research. That Calcium with D3 alone promotes calcium deposits in the lining of blood vessels. However if taking sufficient vitamin K2 the metabolism of Calcium differs and the Calcium is used for bone production thus combatting bone density loss when Testosterone is low or absent.

[Hidden in reply to gottodealwithit]

I wish you good health in the coming years. Is this your first round of Lupron? Seven years ago I was on intermittent, now its full time.

[gottodealwithit in reply to Hidden]

First round of luporn and has salvage radiation IMRT november 2016

[Hidden in reply to gottodealwithit]

OK Gotto,

This is exactly how it began for me. I got the Dx call on New Years Eve 2009. I didn't party that night. But, so what, I'm here today, and expect to blow away my original prognosis of 10-15 years. You will need support, you found it outside your home. Good folks here.

Joe

[gottodealwithit in reply to Hidden]

thanks Joe_Kam

so far things are OK, I work out for 1.5hrs at gym about 4 mornings a week, do a lot of gardening and am involved in a couple of community groups. I am noticing a decline in stamina, a total loss of Libido, ED after Robotic Surgery Dec 2015, some Incontinence. But for the most part life is good. I have done lots of reading on the subject. Thanks for your support, much appreciated.

[pjoshea13 in reply to gottodealwithit]

The knee-jerk reaction to osteoporosis is to tell the patient to take calcium. Presumably, for someone on ADT, the problem is not inadequate intake. & yet, as for countless women, extra calcium is supposed to solve a problem that is not caused by calcium deficiency.

My estimate is that a man will rapidly begin to lose bone mass when estradiol goes below 12 pg/mL. For men on ADT, there may not be enough testosterone to produce that amount.

The corrective is very simple, & Dr. Myers has even spoken of it: low-dose estradiol patches. The one he mentions is the Vivelle-Dot transdermal - lowest dose.

The aim should be to get estradiol to ~20 pg/mL (never above 30).

Together with vitamin K2, vitamin D & a sufficiency of calcium (perhaps from the diet) osteoporosis may be prevented/reversed. (Others will also mention boron, etc.)

At the moment, if you are deficient in anything, it is likely to be estradiol.

Best, -Patrick

[Hidden in reply to pjoshea13]

Patrick,

I get what I thought was a complete workup every month. Estradiol doesn't appear. Should I be asking for it specifically? I understand that it is an estrogen. Can you set me straight?

Thanks, Joe

[pjoshea13 in reply to Hidden]

Joe,

Since estradiol [E2] is still erroneously thought of as a female hormone, doctors rarely measure it in men. Even when there is a loss of BMD.

About ten years ago, it began to be realized that male bone health depended on E2, rather than testosterone [T]. The enzyme aromatase converts T to E2 as needed. Thus, with severe hypogonadism, E2 may be insufficient. T replacement will solve the problem, but E2 is the issue.

You might be interested in paper [1].

It mentions a threshold range of 15 - 25  pg/mL.

From other reading, it seems that serious problems are associated with E2<12 pg/mL

Study [2] gets to the issue:

"This study found that prostate cancer patients treated with transdermal oestradiol for hormonal therapy did not experience the loss in bone mineral density seen with luteinising hormone-releasing hormone agonists."

Both treatments result in castrate T, but bone loss does not occur when E2 is present.

So far, no-one has done a Lupron + low-dose E2 patch study.

-Patrick

[1]ncbi.nlm.nih.gov/pmc/articl...

[2] ncbi.nlm.nih.gov/pubmed/267...

[Hidden in reply to pjoshea13]

Thanks Patrick,

Curiosities up. I'm on Lupron, but I'll throw it by my Onc to check my estradiol level.

Joe