Multiple Myeloma (blood cell cancer) treated by vitamin D - many studies

Multiple myeloma is the most common primary bone cancer
It accounts for 1% of all cancers. It occurs in about 20,000 people in the US each year.
Multiple studies have found that low vitamin D or poor Vitamin D receptor increases risk of MM
Several studies have found that increasing D increases MM survival (helps treat)
Suspect a study of people with high level of Vitamin D will find they have substantially less MM

Far too expensive to have an RCT for MM prevention
Since the incidence of MM is only 7 per 100,000, would need a trial of about 200,000 people lasting > 5 years
   Trial would cost ~$200 million (Based on $25 million VITAL trial of 25,000 people which lasted for 5 years)

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Multiple myeloma about 1.8 X more likely if poor Vitamin D Receptor - Meta-analysis June 2024

Vitamin D receptor gene polymorphisms and multiple myeloma: a meta-analysis
Clin Exp Med. 2024 Jun 4;24(1):118. doi: 10.1007/s10238-024-01382-4.
Chunyi Lyu 1, Xuewei Yin 1, Zonghong Li 1, Teng Wang 1, Ruirong Xu 2 3

Vitamin D acts through the vitamin D receptor (VDR), and vitamin D level decreases in multiple myeloma (MM) patients. Single nucleotide polymorphisms in VDR alter its functions to affect the vitamin D status. This raises the question of whether VDR gene polymorphisms are associated with MM risk, which has been investigated in case‒control studies, but the results have been inconsistent. This meta-analysis aimed to investigate the relationship between VDR gene polymorphisms and MM risk. The PubMed, Web of Science, Medline, Embase, Chinese National Knowledge Infrastructure (CNKI), Chinese Scientific Journal (VIP), Wanfang Databases (WANFANG) were searched from inception to June 1, 2023, without language restriction or publication preference. Pooled odds ratio (OR) and 95% confidence interval (CI) for each variable were calculated. Leave-one-out sensitivity analysis was performed to determine the source of heterogeneity. Publication bias was assessed using Begg' and Egger's tests, and the trim-and-fill method was used to compensate for publication bias. The correlation meta-analysis was conducted using Comprehensive Meta-Analysis 3.0 and STATA 12.0 software. All the included studies were based on Asian populations and involved four VDR gene polymorphisms, TaqI (rs731236), ApaI (rs7975232), BsmI (rs1544410) and FokI (rs2228570).
The results showed that

• TaqI (C vs. T: OR = 1.487, 95% CI 1.052, 2.104, P = 0.025;
• CC + CT vs. TT: OR = 1.830, 95% CI 1.138, 2.944, P = 0.013),
• ApaI (T vs. G: OR = 1.292, 95% CI 1.101, 1.517, P = 0.002;
• TT vs. GG: OR = 1.600, 95% CI 1.106, 2.314, P = 0.013;
• TG vs. GG: OR 1.305, 95% CI 1.050, 1.622; P = 0.016;
• TT + TG vs. GG: OR = 1.353, 95% CI 1.103, 1.662, P = 0.004),
• BsmI (GG vs. AA: OR = 1.918, 95% CI 1.293, 2.844, P = 0.001;
• GA vs. AA: OR = 1.333, 95% CI 1.058, 1.679, P = 0.015;
• G vs. A: OR = 1.398, 95% CI 1.180, 1.657, P = 0.000;
• GG vs. AA + GA: OR = 1.686, 95% CI 1.174, 2.423, P = 0.005), and
• FokI (T vs. C: OR = 1.687, 95% CI 1.474, 1.931, P = 0.000;
• TT vs. CC: OR = 2.829, 95% CI 2.066, 3.872, P = 0.000;
• TC vs. CC: OR = 1.579, 95% CI 1.304, 1.913, P = 0.000,
• TT + TC vs. CC: OR = 1.771, 95% CI 1.477, 2.125, P = 0.000;
• TT vs. CC + TC: OR = 2.409, 95% CI 1.814, 3.200, P = 0.000)

are associated with MM risk.
VDR gene polymorphisms including ApaI, BsmI, TaqI, and FokI are associated with MM risk in Asian populations.
Additional studies with large sample sizes and different ethnicities are needed.
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Multiple Myeloma abut 50% worse if Vitamin D Deficient - April 2024

Prevalence, Outcomes, and Complications of Vitamin D Deficiency Among Patients with Multiple Myeloma: Nationwide Burden of Disease
J Investig Med. 2024 Apr 17:10815589241249998. doi: 10.1177/10815589241249998 PDF behind paywall
Rahul Gujarathi 1, Manisha Rakesh Lakhanpal 2, Nikhila Chelikam 3, Divesh Manjani 4, Simmy Lahori 5, Sai Anusha Akella 6, Prashanth Gumpu Shivashankar 7, Francis Vino Dominic Savio 8, Abdirazak Ibrahim Ali 9, Navyatha Annareddy 10, Aryak Singh 11, Lokesh Manjani 12, Prasanthi Vanga 13, Avinash Adiga 14

Multiple myeloma (MM), constituting 10% of hematological malignancies, poses significant morbidity and mortality, especially with skeletal involvement. Bisphosphonate use in MM may lead to severe hypocalcemia due to vitamin D deficiency (VDD), exacerbating bone marrow plasma cell burden. We aimed to assess VDD prevalence and its impact on outcomes in MM patients. A retrospective cross-sectional analysis (2008-2018) of nationwide inpatient data identified adult MM hospitalizations with VDD using ICD-10-CM codes.

Univariate and multivariate analyses were conducted to evaluate prevalence, demographics, and outcomes, with significance set at p < 0.05.
Among 330,175 MM hospitalizations, 3.48% had VDD.
VDD was more prevalent among

	Univariate	multivariate analyses
50-75-year-olds	61.72%	59.74%
females	53.36%	44.34%
Blacks	23.34%	22.94%
Whites	65.84%	65.79%
higher income brackets	26.13%	23.85%
hypertension	71.12%	69.89%
dyslipidemia	42.47%	34.98%
obesity	13.63%	10.19%
alcohol abuse	.61%	1.34%

In regression analysis, VDD in MM patients correlated with higher morbidity (aOR: 1.24, 95%CI: 1.14-1.36) and major disability (aOR: 1.26, 95%CI: 1.20-1.30). MM patients with VDD exhibit worse outcomes, underscoring the importance of recognizing and managing VDD promptly. Further prospective studies are needed to validate our findings and explore the impact of vitamin D supplementation on MM patient outcomes.

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Vitamin D supplementation (only 1,000 IU) improved Multiple Myeloma remission - Sept 2023

Prevalence and clinical outcomes of vitamin D deficiency among Japanese multiple myeloma patients: a single-center observational study
Support Care Cancer. 2023 Sep 1;31(9):547. doi: 10.1007/s00520-023-08021-w
Atsushi Isoda 1 2, Yuri Miyazawa 3 4, Tetsuya Ishikawa 3 4, Shuhei Kanaya 3 4, Keita Nakayama 3, Masahiro Mihara 3, Hirono Iriuchishima 3, Akio Saito 3, Morio Matsumoto 3, Morio Sawamura 3

Purpose: Vitamin D plays a crucial role in skeletal metabolism and holds significant importance in the pathophysiology of multiple myeloma (MM). This study aimed to determine the prevalence of vitamin D deficiency among Japanese MM patients and its correlation with clinical outcomes.

Methods: Serum 25-hydroxyvitamin D (25(OH)D) levels were assessed in 68 MM patients at a single institution in Japan, analyzing their association with clinical status, laboratory parameters including procollagen type 1 N-propeptide (P1NP) and tartrate-resistant acid phosphatase 5b (TRACP-5b), health-related quality of life (HR-QOL) scores, and overall survival. Additionally, patients with suboptimal 25(OH)D levels received cholecalciferol supplementation (1000 IU/day), and changes in laboratory parameters were monitored.

Results: The median 25(OH)D level was 22 ng/ml, with 32% and 51% of patients exhibiting vitamin D deficiency (< 20 ng/ml) and insufficiency (20-29 ng/ml), respectively. The 25(OH)D levels were unrelated to sex, age, MM stage, or bone lesions, but the vitamin D-deficient group showed a tendency towards lower HR-QOL scores.

Among patients achieving complete remission, vitamin D supplementation increased P1NP, while TRACP-5b remained unchanged. Overall survivals from vitamin D measurement and from MM diagnosis were significantly worse in the vitamin D-deficient group compared to the vitamin D-insufficient/-sufficient group.

Conclusion: The study identified a considerable number of Japanese MM patients with insufficient serum vitamin D levels, with one-third being deficient. Additionally, vitamin D deficiency predicted poor overall survival in Japanese MM patients. Further investigation is required to determine whether vitamin D supplementation can improve the frailty and survival of vitamin D-deficient MM patients.
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Multiple Myeloma associated with low vitamin D - meta-analysis July 2023

The Global Prevalence of Vitamin D Deficiency and Insufficiency in Patients with Multiple Myeloma: A Systematic Review and Meta-Analysis
Nutrients . 2023 Jul 20;15(14):3227. doi: 10.3390/nu15143227.
Nor Hayati Ismail 1, Ali Mussa 1 2, Mutaz Jamal Al-Khreisat 1, Shafini Mohamed Yusoff 1, Azlan Husin 3, Muhammad Farid Johan 1, Md Asiful Islam 4

Background: Multiple myeloma (MM) is a hematological malignancy characterized by the exponential growth of malignant plasma cells. Individuals diagnosed with MM exhibit a deficiency in vitamin D and may suffer fatigue, a loss of muscular strength, persistent musculoskeletal aches, and pain. The objective of this systematic review and meta-analysis is to determine the prevalence of vitamin D insufficiency and deficiency in individuals diagnosed with MM.

Methods: We searched five electronic databases using relevant keywords. The quality of the included studies was evaluated using the critical appraisal tool developed by the Joanna Briggs Institute. We employed a random-effects model and presented the findings in the form of percentages accompanied by 95% confidence intervals (CI). This protocol has been officially registered in PROSPERO under the registration number CRD42021248710.

Results: The meta-analysis comprised a total of eighteen studies and found that, among patients with MM, the occurrence of serum vitamin D deficiency and insufficiency was 39.4% (95% CI: 25.8 to 52.9, n = 3746) and 34.1% (95% CI: 20.9 to 47.2, n = 3559), respectively. The findings indicate that a greater proportion of newly diagnosed patients exhibited vitamin D deficiency and insufficiency, with rates of 43.0% and 41.6%, respectively, compared to those receiving treatment (rates of 41.6% and 32.3%, respectively). The findings of the sensitivity analyses were consistent, and most of the studies (72.2%) were deemed to be of high quality. The results of Egger's test indicated the absence of publication bias.

Conclusions: Patients diagnosed with MM have been found to exhibit significantly elevated levels of both vitamin D deficiency and insufficiency. Therefore, it is recommended to consider vitamin D testing as an additional parameter in the current criteria for the clinical evaluation of MM.
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Vitamin D and Multiple Myeloma: A Scoping Review - March 2023

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Multiple myeloma: Mean Vitamin D level = 5 ng - Dec 2020

Serum Levels of Vitamin D in Patients with Multiple Myeloma
Folia Med (Plovdiv) . 2020 Dec 31;62(4):730-735. doi: 10.3897/folmed.62.e50321
Discusses better response to treatment if have higher level of vitamin D
.  Download the PDF from VitaminDWiki

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Far better MM survival when getting just 10,000 IU of Vitamin D per WEEK - Oct 2015

Prevalence, Supplementation, and Impact of Vitamin D Deficiency in Multiple Myeloma Patients.
Cancer Invest. 2015 Oct 27:1-5. [Epub ahead of print]
Group given the most vitamin D had the best survival
   However, results were not statistically significant (too small of study)

Note: Dose size was only about 10,000 IU per WEEK - which they realized at the end of the study was far too little
Lauter B1, Schmidt-Wolf IG1.
1a Department of Internal Medicine III, Center for Integrated Oncology (CIO), University Hospital Bonn , Bonn , Germany.

Here, we studied 83 unselected multiple myeloma patients from December 2007 through December 2014.

• Lower 25(OH) D levels (<10 ng/mL) were associated with higher number of plasma cells in the bone marrow.

Supplementation of vitamin D was accompanied with a significant increase in

• hemoglobin (11.8 to 12.3 p = .039),
• leukocyte (4.9 to 5.8 p = .011), and
• erythrocyte (3.8 to 4.0 p = .004) levels,

while thrombocytes (200.5 to 175.2 p = .036) decreased.

In conclusion, the present study found a high incidence of vitamin D deficiency and insufficiency in MM patients. In myeloma patients, vitamin D levels and supplementation should be more widely taken into account.
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Multiple myeloma 5.3 X more likely in Afgans with a poor Vitamin D Receptor - June 2013

Role of vitamin D receptor (VDR) polymorphisms in susceptibility to multiple myeloma in ethnic Kashmiri population
Blood Cells Mol Dis. 2013 Jun;51(1):56-60. doi: 10.1016/j.bcmd.2013.02.001.
Syed Shafiaa, Iqbal Qasima, Sheikh Aejaz Azizb, Imtiyaz A. Bhata, Syed Nisarb, Zafar Amin Shaha, , ,

Background: Vitamin D regulates many biological processes including bone metabolism, innate immune response, and cell proliferation and differentiation by binding to its receptor VDR. Vitamin D receptor (VDR) gene polymorphisms have been associated with many cancers like breast, colorectal, prostate, and skin. The main aim of this study was to determine whether VDR polymorphisms (ApaI, BsmI and FokI) are associated with increased risk of multiple myeloma.

Methods: We designed a case control study where 75 multiple myeloma cases were studied for VDR polymorphisms (ApaI, BsmI and FokI) against 150 controls taken from general population. The polymorphisms of VDR gene were investigated using PCR–RFLP method.

Results: We did not find any significant association between ApaI and BsmI polymorphisms and multiple myeloma risk (P > 0.05), but FokI polymorphism was significantly associated with increased risk for multiple myeloma. We also found a significant association between the ff variant genotype with creatinine levels, albumin levels, and Durie–Salmon stage III.

Conclusion: Our findings suggest that the FokI polymorphism is involved in the increased susceptibility to development and progression in multiple myeloma in the ethnic Kashmiri population. Furthermore these results suggest that ff genotype is associated with higher risk for developing multiple myeloma.

PDF (which has the 5.3 X factor) can be rented at DeepDyve
See Vitamin D Receptor in VitaminDWiki
55 health problems are greatly increased if poor VDR

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Multiple myeloma 2 X more likely if poor Vitamin D Receptor - May 2019

 Download the PDF from sci-hub via VitaminDWiki

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87+ Vitamin D Receptor pages with CANCER etc. in title

This list is automatically updated

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Multiple myeloma more common in areas with low UVB (Vitamin D) - 2014

Are low ultraviolet B and vitamin D associated with higher incidence of multiple myeloma?
J Steroid Biochem Mol Biol. 2015 Apr;148:245-52. doi: 10.1016/j.jsbmb.2014.12.005
Mohr SB1, Gorham ED1, Garland CF2, Grant WB3, Garland FC1, Cuomo RE4.
Author information
1Deartment of Family and Preventive Medicine, University of California, San Diego, La Jolla, CA, United States; Naval Health Research Center, San Diego, CA, United States.
2Deartment of Family and Preventive Medicine, University of California, San Diego, La Jolla, CA, United States.
3Sunlight, Nutrition, and Health Research Center, San Francisco, CA, United States.
4Deartment of Family and Preventive Medicine, University of California, San Diego, La Jolla, CA, United States; Graduate School of Public Health, San Diego State University, San Diego, CA, United States. Electronic address: raphael.e.cuomo at gmail.com.

BACKGROUND:
The purpose of this study was to determine whether an inverse association exists between latitude, solar ultraviolet B (UVB) irradiance, and incidence rates of multiple myeloma.

Methods Associations of latitude and UVB irradiance with age-standardized incidence rates of multiple myeloma were analyzed for 175 countries while controlling for sex-specific obesity prevalence, cigarette consumption, and alcohol consumption using multiple linear regression.

Results Incidence rates of multiple myeloma were greater at higher latitudes (R(2) for latitude for males=0.31, p<0.0001; females R(2)=0.27, p<0.0001). In regression models for males (R(2)=0.62, p<0.0001) and females (R(2)=0.51, p<0.0001), UVB irradiance was independently inversely associated with incidence rates.

Conclusions Age-adjusted incidence rates of multiple myeloma were higher in countries with lower solar UVB irradiance. Further investigation is warranted in individuals of the association of prediagnostic serum 25(OH)D with risk.

MM prevelance after correction for age

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MM: Vitamin D is low, supplementation helps - Nov 2015

Prevalence of Vitamin D Deficiency in Patients with Bone Metastases and Multiple Myeloma.
Anticancer Res. 2015 Nov;35(11):6281-5.
Maier GS1, Horas K2, Kurth AA3, Lazovic D4, Seeger JB5, Maus U4.
1 University Hospital of Orthopaedic Surgery, Pius-Hospital, Carl-von-Ossietzky-University, Oldenburg, Germany gerrit.maier at uni-oldenburg.de.
2 ANZAC Research Institute, University of Sydney at Concord, Sydney, NSW, Australia.
3 Department of Orthopaedic Surgery, Themistocles Gluck Hospital, Ratingen, Germany.
4 University Hospital of Orthopaedic Surgery, Pius-Hospital, Carl-von-Ossietzky-University, Oldenburg, Germany.
5 Department of Orthopaedic Surgery, Justus-Liebig-University, Giessen, Germany.

BACKGROUND/AIM: Breast and prostate cancer are amongst the most prevalent malignancies globally and up to 40% of patients will develop metastatic disease, particularly to the skeleton. Multiple myeloma is the most common cancer to affect bone with up to 90% of patients developing bone lesions. Although several studies demonstrated that endocrine changes such as vitamin D deficiency promote secondary cancer growth in bone, relatively few have reported its prevalence. For this reason, the purpose of the present study was to evaluate the prevalence of hypovitaminosis D in patients with bone metastases and multiple myeloma.

PATIENTS AND METHODS: Serum 25-OH-D levels of patients with metastatic bone disease were measured on admission. Statistical analyses was performed to evaluate for possible confounders of hypo-vitaminosis D.

RESULTS: We found a widespread and alarming rate of vitamin D deficiency in patients with metastatic bone disease and multiple myeloma. Of note, patients with bone metastases due to breast cancer, prostate cancer and multiple myeloma rarely reached sufficient serum 25-OH-D levels.

CONCLUSION: It is of utmost clinical importance to assess vitamin D levels in cancer patients, especially in those with, or at high risk of developing metastatic bone disease.

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See also VitaminDWiki

• Blood cell cancer is associated with a 3X worse Vitamin D Receptor – June 2019
• Overview Cancer and vitamin D has the following chart

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Incidence of Multiple Melanoma doubled in 30 years

Myelomacrowd

Increased obesity, dark skin, seniors, decreased vitamin D

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Wikipedia on Multiple Myeloma

https://en.wikipedia.org/wiki/Multiple_myeloma

• Multiple myeloma develops in 6.1 per 100,000 people per year
• 2nd most common hematological malignancy in the U.S.
• The five year survival rate is 45%.(with treatment, 6 months if no treatment)
• Is twice as common in African Americans (who have low levels of vitamin D) as it is in White Americans
• Bone pain affects almost 70% of patients and is the most common symptom

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See also web

• A Retrospective Analysis of the Prevalence and Clinical Outcomes of Vitamin D Deficiency in Myeloma Patients in Tropical Australia - March 2020 - DOI: 10.1007/s00520-019-04942-7,"Patients with vitamin D deficiency had a higher likelihood of peripheral neuropathy compared with their non-vitamin D counterparts (73% vs. 33%, P = 0.03)"
• Vitamin D Receptor Gene Polymorphism Is Associated With Multiple Myeloma" Jan 2020, DOI: 10.1002/jcb.29135 3X more likely to have a poor Vitamin D Receptor

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