Vitamin D status & inflammation in PCa

[pjoshea13]

New study [1] below.

... "Serum 25-(OH)D was lower in patients with prostate cancer."

... "Moreover, serum 25(OH)D was {lowest} in patients with severe prostate cancer ..."

... "serum C-reactive protein (CRP) and interleukin (IL)-8, two inflammatory molecules, were elevated in patients with prostate cancer"

... "Serum 25-(OH)D was negatively correlated with serum CRP and IL-8 in patients with prostate cancer."

Conclusion: "Inflammation may be an important mediator for prostate cancer progression in patients with low vitamin D status."

From a 2010 vitamin D / PCa paper [2]:

"Functional analysis by pathway or Gene Set Analysis revealed early suppression of WNT, Notch, NF-kB, and IGF1 signaling. Transcripts related to inflammation were suppressed at 6 h (e.g. IL-1 pathway) and suppression of proinflammatory pathways continued at later time points (e.g. IL-17 and IL-6 pathways)."

Suppression of NF-kB would be sufficient to lower inflammation IMO.

It's good to see confirmation in a human study.

-Patrick

[1] ncbi.nlm.nih.gov/pubmed/284...

Oncotarget. 2017 Mar 28;8(13):22076-22085. doi: 10.18632/oncotarget.16195.

Low vitamin D status is associated with inflammation in patients with prostate cancer.

Xie DD1, Chen YH2, Xu S1, Zhang C3, Wang DM1, Wang H3, Chen L1, Zhang ZH3, Xia MZ4, Xu DX3, Yu DX1.

Author information

1

Department of Urology, Second Affiliated Hospital, Anhui Medical University, Hefei 230022, China.

2

Department of Histology and Embryology, Anhui Medical University, Hefei 230032, China.

3

Department of Toxicology, Anhui Medical University, Hefei 230032, China.

4

Life Science College, Anhui Medical University, Hefei 230032, China.

Abstract

Vitamin D deficiency has been associated with increased risks of prostate cancer. Nevertheless, the mechanisms remain unclear. The aim of this study was to analyze the association among prostate cancer, vitamin D status and inflammation. Sixty patients with newly diagnosed prostate cancer and 120 age-matched controls were recruited for this study. Vitamin D status was evaluated and serum inflammatory molecules were measured. Serum 25-(OH)D was lower in patients with prostate cancer. Moreover, serum 25(OH)D was lower in patients with severe prostate cancer than patients with mild and moderate prostate cancer. By contrast, serum C-reactive protein (CRP) and interleukin (IL)-8, two inflammatory molecules, were elevated in patients with prostate cancer. Serum 25-(OH)D was negatively correlated with serum CRP and IL-8 in patients with prostate cancer. Additional analysis showed that the percentage of vitamin D receptor positive nucleus in the prostate was reduced in patients with prostate cancer. By contrast, the percentage of nuclear factor kappa B p65-positive nucleus was elevated in patients with prostate cancer. Our results provide evidence that there is an association among prostate cancer, vitamin D deficiency and inflammatory signaling. Inflammation may be an important mediator for prostate cancer progression in patients with low vitamin D status.

KEYWORDS:

inflammation; nuclear factor kappa B p65; prostate cancer; vitamin D deficiency; vitamin D receptor

PMID: 28423553 DOI: 10.18632/oncotarget.16195

[2] ncbi.nlm.nih.gov/pubmed/?te...

BMC Genomics. 2010 Jan 13;11:26. doi: 10.1186/1471-2164-11-26.

1,25 dihydroxyvitamin D-mediated orchestration of anticancer, transcript-level effects in the immortalized, non-transformed prostate epithelial cell line, RWPE1.

Kovalenko PL1, Zhang Z, Cui M, Clinton SK, Fleet JC.

Author information

1

Department of Foods and Nutrition and the Interdepartmental Nutrition Program, Purdue University, West Lafayette, IN 47907-2059, USA.

Abstract

BACKGROUND:

Prostate cancer is the second leading cause of cancer mortality among US men. Epidemiological evidence suggests that high vitamin D status protects men from prostate cancer and the active form of vitamin D, 1alpha,25 dihydroxyvitamin D3 (1,25(OH)2D) has anti-cancer effects in cultured prostate cells. Still, the molecular mechanisms and the gene targets for vitamin D-mediated prostate cancer prevention are unknown.

RESULTS:

We examined the effect of 1,25(OH)2D (+/- 100 nM, 6, 24, 48 h) on the transcript profile of proliferating RWPE1 cells, an immortalized, non-tumorigenic prostate epithelial cell line that is growth arrested by 1,25(OH)2D (Affymetrix U133 Plus 2.0, n = 4/treatment per time and dose). Our analysis revealed many transcript level changes at a 5% false detection rate: 6 h, 1571 (61% up), 24 h, 1816 (60% up), 48 h, 3566 (38% up). 288 transcripts were regulated similarly at all time points (182 up, 80 down) and many of the promoters for these transcripts contained putative vitamin D response elements. Functional analysis by pathway or Gene Set Analysis revealed early suppression of WNT, Notch, NF-kB, and IGF1 signaling. Transcripts related to inflammation were suppressed at 6 h (e.g. IL-1 pathway) and suppression of proinflammatory pathways continued at later time points (e.g. IL-17 and IL-6 pathways). There was also evidence for induction of anti-angiogenic pathways and induction of transcripts for protection from oxidative stress or maintenance of cell redox homeostasis at 6 h.

CONCLUSIONS:

Our data reveal of large number of potential new, direct vitamin D target genes relevant to prostate cancer prevention. In addition, our data suggests that rather than having a single strong regulatory effect, vitamin D orchestrates a pattern of changes within prostate epithelial cells that limit or slow carcinogenesis.

PMID: 20070897 PMCID: PMC2820456 DOI: 10.1186/1471-2164-11-26

[Indexed for MEDLINE] Free PMC Article

[Sisira]

The contents of this article are very useful and the mention of Vitamin D should be an eye-opener for all who take various treatments for prostate cancer.

After my diagnosis for PCa in 2015, no sooner I started my treatment, I came to know about the importance of Vitamin D. Certainly not form my Oncologist! But from my own research in the internet. So I met with an Endocrinologist and requested him to check my serum Vitamin D level. He had no idea about its connection with the PCa. He ordered the blood test Vitamin D3 ( 25 Hydroxy Cholecalciferol ) and my test result was 22.6 ng/mL.

Deficiency : Below 10.ng/mL Insufficiency : 10 - 30 ng/mL Sufficiency : 30 - 100 ng/mL and Hypervitaminosis : Above 100 ng/mL

I told him the ideal level conducive for PCa treatment is 60 - 80 ng/mL and to raise my insufficient level. He prescribed a 3 months injection course : Vitamin D3 - 30,000 iu monthly. He also gave me a very good advice, that I should check my blood calcium level with the high dose supplementation since increase in Vitamin D can also raise the blood calcium levels and excessive calcium can be very harmful. So an additional blood test was needed which was "Calcium - ionized ". The two tests after 3 months read as - Vitamin D3 : 90.2ng/mL and Calcium - Ionized : 5.04 ( Normal range : 4.36 - 5.20 ng/dl ). He then fixed a management dose of 4000iu Vitamin D3 to be taken orally daily to achieve my desired goal. Both tests were done every 6 months and now my Vitamin D3 level is stable around 70 ng/mL and no undue increase in blood calcium. For your practical use I would like to summarize below few points :

- Vit. D is a very good immunity booster.

- Vit. D helps body to use calcium and phosphorous to make strong bone and teeth.

- Vit. D is a natural cancer cure : It is a silver bullet which can enter even the cell nucleus and repair the mutated DNA inducing the programmed cell death ( apoptosis ) and all what Patrick has said in his write-up. ( Please don't start taking loads of Vit.D3 ! )

- Test for Vit. D is D3 ( 25 Hydroxy Cholecalciferol )

- Serum levels are given above ( 60 - 80 ng/mL : ideal during PCa treatment )

- During supplementation, blood calcium ( ionized ) should also be checked ( Levels given above )

- Vit. D3 supplementation should not exceed a maximum dosage of 4000iu for a day (Doctor's advice)

- Vitamin D3 blood test is relatively expensive : $70

- Vitamin D3 supplementation on the other hand is very cheap : 30000 iu injection : $2 only! Tablets for 1 month : $15

These costs may be different in your countries.

Thanks Patrick. I hope I didn't contradict you.

[pjoshea13 in reply to Sisira]

Sisira,

See my post on hypervitaminosis D in this thread.

With adequate viamin K2, calcium will not be elevated.

=Patrick

[rococo in reply to Sisira]

When my vit d 25 hydro. Was around 100 aftewitch cat scan. calcification of the arteries. Cut the dose and added k 2 from natto to the vit d3. My next ct scan less calcification. The 50 and sometimes 200 mg of vit k2 took the calcium out of the arteries and into the bones I hope. All related to blood thinners , blood clots and strokes. Complicated stuff. Try to vit.d25 hydrox around 60 to 70 with 4 to 6000 iu vit d3 along with 50 mcg not mg as stated above. My mistake . k2 is measured micograms

Not milligrams

o

[Sisira in reply to rococo]

Thank you rococo. I accept your clarification as right. Presently I maintain Vit. D3 around 70 ng/mL with 4000iu daily supplementation whilst keeping my ionized calcium level within the normal levels. I hope within these safe levels no calcification of arteries will take place. Thank you also for indicating the proper dosages of Vit.K2 to be used in case of necessity. I think merely in the hope of fighting PCa with Vit.D, it is dangerous to take a supplementation daily dose as high as 10,000 - 15,000 iu not knowing where we will end up unless you are quite sure your serum D3 level will remain stable at 70 - 90 ng/mL range.

[WinnipesaukeeBob]

VItamin D3 is one of the simplest and safest components of fighting PC. Just take 10,000iu per day if you get some sun during the day, 15,000iu if you do not. The level of D in your blood will increase to and remain in the 70-90 range where you will have more energy and less inflamation.

Little D3 gel caps are fine. They cost $20 a year. No need for vitamin d shots, or for quarterly testing.

Wobenzyme, nattokinase, and serrapeptase are also very effective at increasing blood flow and reducing inflamation and pain. The natto also breaks up clots of all kinds, with some research suggesting it retards PC tumor formation. What I am sue of is you will feel better and enjoy better movement.

Bob

[DanR3254]

I was in a study at Roswell Park Cancer Institute using VitD at varying doses. I was at 10,000 I/U per day for a couple of years. My doubling time went from 3-4 months to about 18 months. I stopped taking it when my VitD level hit 140, 100 is considered toxic. Here is a current trial they are performing. roswellpark.org/clinical-tr...

[pjoshea13]

Cautionary tale:

A man in another group sent me a note saying that he had been told to stop supplementing because of "vitaminosis D". His D was only ~35.

Vitaminosis D shows itself as elevated calcium in the blood. I asked if he was taking vitamin K2. He had been, but had stopped a year earlier. Vitaminosis D does not occur when the K status is good.

Vitaminosis D is poorly named.

-Patrick

[Sisira]

Thanks. All the posts are informative. I think my endocrinologist gave Vit.D3 IV to raise the deficient level with a high dose of 30000 to achieve a good result within a short period of 3 months and then follow with a daily safe oral dose which really worked. Taking very high doses of vitamins or for that matter any other chemical substances needs regular blood check ups as advised by doctors to avoid serious issues of Metabolic Syndrome. Vitamin D3 and its effect on PCa is not the only story! !5000iu per day appears to me as relatively high unless there are proper checks and balances and also it is only for a therapeutic short period. I have seen in several medical books on PCa management the safe Vit. D supplementation level as 4000 - 5000 iu per day for long-term use. Thanks Patrick, I have noted down your advice to maintain Vit.K2 level to avoid any Calcium problem.

[rococo]

From the wealth of info on the topic of these sulplements, thefficiency with which each person will process them will be different. It can be quit difficult to discern that so I always start out low and titrate up till optimal effect. The docs often use this protocol when they with dosing.