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Overview Sickle Cell and Vitamin D

Several Sickle Cell trials have found that a loading dose of vitamin D followed by a good sized maintence dose greatly reduces the number of days of SC pain

  • The size of the loading and maintence doses should vary by weight and health.
  • One study used a loading dose 100,000 IU weekly for 6 weeks - ignoring weight
  • One study used a loading dose of 5,234 IU/kg for 4 days
  • Perhaps $10 of Vitamin D per year can substantially reduce the $14,700 a year cost of Sickle Cell

See also Vitamin D Life

Overview Loading of vitamin D contains the following

Loading dose: 153 studies at Vitamin D Life

Vitamin D loading dose (stoss) proven to improve health overview
If a person is or is suspected to be, very vitamin D deficient a loading dose is typically given

  • Loading = restore = quick replacement by 1 or more doses
  • Loading doses range in total size from 100,000 IU to 1,000,000 IU of Vitamin D3
    • = 2.5 to 25 milligrams
  • The size of the loading dose is a function of body weight - see below
    • Unfortunately, some doctors persist in using Vitamin D2 instead of D3
  • Loading may be done as quickly as a single day (Stoss), to as slowly as 3 months.
    • It appears that spreading the loading dose over 4+ days is slightly better if speed is not essential
  • Loading is typically oral, but can be Injection (I.M,) and Topical
  • Loading dose is ~3X faster if done topically or swished inside of the mouth
    • Skips the slow process of stomach and intestine, and might even skip liver and Kidney as well
  • The loading dose persists in the body for 1 - 3 months
    • The loading dose should be followed up with on-going maintenance dosing
    • Unfortunately, many doctors fail to follow-up with the maintenance dosing.
  • About 1 in 300 people have some form of a mild allergic reaction to vitamin D supplements, including loading doses
    • it appears prudent to test with a small amount of vitamin D before giving a loading dose
    • The causes of a mild allergic reaction appear to be: (in order of occurrence)
    • 1) lack of magnesium - which can be easily added
    • 2) allergy to capsule contents - oil, additives (powder does not appear to cause any reaction)
    • 3) allergy to the tiny amount of D3 itself (allergy to wool) ( alternate: D3 made from plants )
    • 4) allergy of the gut to Vitamin D - alternative = topical

Items in both categories of Bone Health and Dark Skin (a proxy for Sickle Cell) are listed below

Sickle cell + 4 days of 5,234 IU/kg of vitamin D ==> not deficient - Dec 2014

Vitamin D deficiency and its correction in children with sickle cell anaemia.
Ann Hematol. 2014 Dec;93(12):2051-6. doi: 10.1007/s00277-014-2144-7. Epub 2014 Jul 2.
Wykes C1, Arasaretnam A, O'Driscoll S, Farnham L, Moniz C, Rees DC.
1Department of Paediatric Haematology, King's College Hospital, King's College London, Denmark Hill, London, SE5 9RS, UK.

Vitamin D deficiency is common in sickle cell anaemia (SCA, HbSS), although its significance and optimal means of correction are unknown. We conducted an audit to assess the clinical significance of 25-hydroxy vitamin D (25-OHD) deficiency in children with SCA and to evaluate two methods of vitamin D supplementation. We audited 25-OHD levels in 81 children with SCA and looked for statistical associations with biochemical, haematological and clinical parameters. In a separate group of regularly transfused children with SCA, we compared changes in 25-OHD blood concentrations following treatment with either high-dose intramuscular ergocalciferol (n = 15) or 4 days of high-dose oral cholecalciferol (n = 64). Ninety-one percent of children with SCA had 25-OHD levels <20 μg/L. The 25-OHD levels were negatively correlated with increasing age (P < 0.001) but showed no significant relationship to laboratory measurements, transcranial Doppler velocities or hospital attendance. Both intramuscular ergocalciferol and oral cholecalciferol supplementations resulted in increases of 25-OHD blood concentration to normal levels. The mean dose of ergocalciferol was greater than that of cholecalciferol (7,729 versus 5,234 international units (IU)/kg, P < 0.001), but the increment in 25-OHD levels was significantly greater in the oral cholecalciferol group (6.44 versus 2.82 (ng/L)/(IU/kg), P < 0.001).
Both approaches resulted in vitamin D sufficiency for about 120 days.
Increased 25-OHD concentration was significantly associated with increased serum calcium concentration. Vitamin D deficiency is very common in SCA and can be effectively corrected with high-dose intramuscular ergocalciferol or 4 days of high-dose oral cholecalciferol. Prospective, randomised studies are needed to assess the clinical value of vitamin D supplementation.

PMID: 24981689 DOI: 10.1007/s00277-014-2144-7 Publisher wants $40 for the PDF

Prevalence of Vitamin D Deficiency in Sickle Cell Disease: A Systematic Review

PLOS One March 3, 2015DOI: 10.1371/journal.pone.0119908
Vikki G. Nolan , Kerri A. Nottage, Elliott W. Cole, Jane S. Hankins, James G. Gurney
Prevalence of Vitamin D Deficiency in Sickle Cell Disease: A Systematic Review
Vikki G. Nolan, Kerri A. Nottage, Elliott W. Cole, Jane S. Hankins, James G. Gurney PLOS x

Vitamin D deficiency has emerged as a public health focus in recent years and patients with sickle cell disease (SCD) reportedly have a high prevalence of the condition. Our objectives were to summarize definitions of vitamin D deficiency and insufficiency used in the literature, and to determine the prevalence and magnitude of each in patients with SCD through a systematic review conducted according to PRISMA guidelines. From a PubMed search, 34 potential articles were identified and 15 met eligibility criteria for inclusion. Definitions of deficiency and insufficiency varied greatly across studies making direct comparisons difficult. This review provides evidence to suggest that suboptimal vitamin D levels are highly prevalent among those with SCD, far more so than in comparable non-SCD patients or matched control populations.
Defining deficiency as vitamin D <20ng/mL, prevalence estimates in SCD populations range from 56.4% to 96.4%.
When compared with results from the population-based National Health and Nutrition Examination Survey, however, the general African American population appeared to have a similarly high prevalence of vitamin D deficiency. African American patients with and without SCD were both substantially higher than that of Caucasians. What remains to be determined is whether there are adverse health effects for patients with SCD because of concurrent vitamin D deficiency.

Discussion (from the PDF)
Vitamin D deficiency is one of the most common nutritional conditions among persons with SCD [2,25,26] and there are characteristics specific to SCD that may contribute to this phenomenon including decreased appetite [27,28], inability to absorb nutrients due to damage to the intestinal mucosa [29,30], as well as an increased basal metabolic rate and higher nutritional demands to sustain normal physiologic functioning [31–39]. Vitamin D deficiency has been associated with bone health [5,6], cardiovascular disease [7–9], asthma [10–12], nephropathy [1,13], and chronic pain [14–19] and individuals with SCD are susceptible to all of these complications [20–24]. While the role of vitamin D deficiency as a contributing factor in these complications is unclear, vitamin D deficiency can be reliably and inexpensively treated, making it a prime intervention to potentially improve health outcomes among those with SCD.

 Download the PDF from Vitamin D Life

Diseases associated with Sickle Cell (and low vitamin D)

Vitamin D deficiency and comorbidities in children with sickle cell anemia.
Pediatr Hematol Oncol. 2012 Apr;29(3):261-6. doi: 10.3109/08880018.2012.661034.
Jackson TC1, Krauss MJ, Debaun MR, Strunk RC, Arbeláez AM.
1Department of Pediatrics, Washington University School of Medicine and St. Louis Children's Hospital, St. Louis, Missouri, USA.

Vitamin D deficiency is known to be common among patients with sickle cell anemia (SCA). Vitamin D levels were measured in 139 children (aged 7.9 to 15.1 years) to study its association with SCA morbidities; severe deficiency <10 ng/mL was present in 64.0% and only 2.2% were sufficient (>30 ng/mL). Vitamin D levels were associated with pulmonary function (forced expiratory volume in 1 second [FEV(1)]), but not associated with either rates of acute pain or acute chest syndrome episodes. Further studies are needed to be able to compare outcomes in those with deficiency to those with sufficiency, as well as to treating patients with SCA with vitamin D to better establish a possible link, if any, between vitamin D and SCA morbidity.

PMID: 22475302 PMCID: PMC3640358 DOI: 10.3109/08880018.2012.661034
 Download the PDF from Vitamin D Life

Sickle Cell pain reduced for 6 months by 100,000 IU vitamin D weekly for 6 weeks - Oct 2015

Note by VitaminDWik - Loading dose can only be expected to last for 2-3 months, not 6 months
High dose vitamin D therapy for chronic pain in children and adolescents with sickle cell disease: results of a randomized double blind pilot study.
Br J Haematol. 2012 Oct;159(2):211-5. doi: 10.1111/bjh.12019. Epub 2012 Aug 28.
Osunkwo I1, Ziegler TR, Alvarez J, McCracken C, Cherry K, Osunkwo CE, Ofori-Acquah SF, Ghosh S, Ogunbobode A, Rhodes J, Eckman JR, Dampier C, Tangpricha V.
1Aflac Cancer and Blood Disorders Center of Children's Healthcare of Atlanta, 1405 Clifton Road NE, Atlanta, GA 30322, USA. ify.osunkwo at choa.org
Far fewer days of pain between visits until Vitamin D loading dose wore off
We report results of a pilot study of high-dose vitamin D in sickle cell disease (SCD). Subjects were given a 6-week course of oral high-dose cholecalciferol (4000-100 000 IU per week) or placebo and monitored prospectively for a period of six months. Vitamin D insufficiency and deficiency was present at baseline in 82·5% and 52·5% of subjects, respectively. Subjects who received high-dose vitamin D achieved higher serum 25-hydroxyvitamin D, experienced fewer pain days per week, and had higher physical activity quality-of-life scores. These findings suggest a potential benefit of vitamin D in reducing the number of pain days in SCD. Larger prospective studies with longer duration are needed to confirm these effects.
PMID: 22924607 PMCID: PMC3460143 DOI: 10.1111/bjh.12019
 Download the PDF from Vitamin D Life

Global Burden of Sickle Cell Anaemia in Children under Five, 2010–2050

PLOS One July 2013 - the word vitamin does not occur in the PDF
 Download the PDF from Vitamin D Life

Very low levels of vitamin D in Sickle Cell Patients, lower than just dark skin - March 2017

Vitamin D Deficiency in Adult Sickle Cell Patients
Journal of National Medical Association, Spring 2017Volume 109, Issue 1, Pages 36–43
Study just observes the association, but makes no comment about cause ==> effect
 Download the PDF from Vitamin D Life

Sickle Cell events dropped from 4 per year to 1.5 yer year by monthly 100,000 IU - RCT May 2018

Randomized phase 2 trial of monthly vitamin D to prevent respiratory complications in children with sickle cell disease.
Blood Adv. 2018 May 8;2(9):969-978. doi: 10.1182/bloodadvances.2017013979.
Lee MT1, Kattan M2, Fennoy I3, Arpadi SM4,5, Miller RL6,7, Cremers S8, McMahon DJ8, Nieves JW5, Brittenham GM1.
 Download the PDF from Vitamin D Life
Reduction in SC events
In sickle cell disease, respiratory infection and asthma may lead to respiratory complications that are a leading cause of morbidity and mortality. Vitamin D has anti-infective and immunomodulatory effects that may decrease the risk for respiratory infections, asthma, and acute chest syndrome. We conducted a randomized double-blind active-controlled clinical trial to determine whether monthly oral vitamin D3 can reduce the rate of respiratory events in children with sickle cell disease. Seventy sickle cell subjects, ages 3-20 years, with baseline records of respiratory events over 1 year before randomization, underwent screening. Sixty-two subjects with 25-hydroxyvitamin D levels of 5-60 ng/mL were randomly assigned to oral vitamin D3 (100 000 IU or 12 000 IU, n = 31 each) under observed administration once monthly for 2 years. The primary outcome was the annual rate of respiratory events (respiratory infection, asthma exacerbation, or acute chest syndrome) ascertained by the use of a validated questionnaire administered biweekly. Analysis included 62 children (mean age of 9.9 years, 52% female, and predominantly with homozygous HbS disease [87%]) with mean baseline 25-hydroxyvitamin D of 14.3 ng/mL. The annual rates of respiratory events at baseline and intervention years 1 and 2 were 4.34 ± 0.35, 4.28 ± 0.36, and 1.49 ± 0.37 (high dose) and 3.91 ± 0.35, 3.34 ± 0.37, and 1.54 ± 0.37 (standard dose), respectively. In pediatric patients with sickle cell disease, 2-year monthly oral vitamin D3 was associated with a >50% reduction in the rate of respiratory illness during the second year (P = .0005), with similar decreases associated with high- and standard-dose treatment. This trial was registered at www.clinicaltrials.gov as #NCT01443728.

PMID: 29712666 DOI: 10.1182/bloodadvances.2017013979
Note by founder of Vitamin D Life
Would have gotten much better response if any of the following:

1) Had used a gut-friendly form of vitamin D - about 40% increased response
2) Had dosed bi-weekly instead of monthly - about 20% increased response
3) Had taken the dose just before or during the largest meal of the day - about 30% increased response

See also web

Quick summary of SC problems (Image from the web)

Attached files

ID Name Comment Uploaded Size Downloads
9804 SC events.jpg admin 05 May, 2018 12:49 24.83 Kb 1236
9788 100,000 IU per month.jpg admin 02 May, 2018 16:38 22.09 Kb 1326
9786 sickle cell monthly 200,000 IU.pdf admin 02 May, 2018 16:33 1,018.49 Kb 736
7805 SC boy.jpg admin 06 Mar, 2017 16:24 9.04 Kb 1828
7804 comorbidities in children with sickle cell.pdf PDF admin 06 Mar, 2017 15:56 281.96 Kb 647
7803 SC pain days.jpg admin 06 Mar, 2017 15:37 16.93 Kb 1982
7802 sickle cell - 2014.pdf PDF admin 06 Mar, 2017 14:39 541.89 Kb 590
7801 Sickle Cell and vitamin D.pdf PDF 2017 admin 06 Mar, 2017 14:11 631.79 Kb 727
5116 Global Burden of SCD.pdf PDF 2013 admin 04 Mar, 2015 03:00 1.81 Mb 848
5115 Sickle cell disease.pdf PDF 2015 admin 04 Mar, 2015 02:39 749.73 Kb 930
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