The Importance of Vitamin D-Part 3
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Welcome to Part 3 of our series on the importance of Vitamin D. In this final installment, we will delve into the methodologies and interpretations of Vitamin D research, highlighting the critical issues that can lead to confusion and missed therapeutic opportunities. We will explore the need for specialized training among physicians and researchers, proper dosing and study durations, and the impact of factors such as variability in study populations and inadequate funding.
Additionally, we will discuss the 2017 Vitamin D Supplementation Guidelines and review numerous studies and protocols that support a broad range of clinical applications for Vitamin D supplementation.
Flawed Designed Studies
The methodologies and interpretations of vitamin D research often do not meet the highest standards, which leads to confusion and missed chances for its therapeutic use. This suggests that research designs concerning vitamin D are often inadequate, necessitating a more thorough understanding of the outcomes. As a result, the potential of vitamin D in treating certain conditions is not fully acknowledged, leading to neglected opportunities for its beneficial application.
Let's take a brief look at these problems:
The Training Gap
Physicians' and researchers' need for specialized training in nutrition is crucial, as it significantly affects their ability to interpret lab results accurately and design and analyze studies on vitamin D. This deficiency in training often leads to methodological errors, such as incorrect dosing, inadequate study durations, and improper participant selection. Without a deep understanding of nutritional science, researchers may fail to account for factors influencing vitamin D metabolism, such as dietary intake, sunlight exposure, and genetic variations.
Consequently, studies may yield unsubstantiated conclusions that do not reflect the true potential of vitamin D. Improving training in nutrition can enhance the quality of research, leading to more accurate and reliable findings that better inform clinical practices and public health policies.
Dose and Duration Issues
Many studies on vitamin D use doses that are too low and durations that are too short to capture the full effects. These inadequate dosing regimens can lead to weak results, falsely suggesting that vitamin D supplementation is ineffective. For example, a study that administers only 400 IU of vitamin D daily over a few weeks may not show significant health benefits. In contrast, a higher dose over several months may improve health outcomes.
Properly designed studies with adequate dosing and longer durations are critical to understanding the true effects of vitamin D. Such studies can reveal the vitamin's potential in preventing and treating various conditions, providing clearer guidance for supplementation.
Misleading Results
Inadequate research on vitamin D can lead to underestimation of its significant advantages, which are known for its efficacy and safety. Defective study designs, such as those with inappropriate dosages or short study durations, can result in data misinterpretation. This misinterpretation can mislead both the public and healthcare professionals, causing them to overlook the potential benefits of vitamin D. For instance, if a poorly designed study concludes that vitamin D has no impact on bone health, it may discourage further research and supplementation efforts.
Ensuring vigorous study designs and accurate data interpretation is essential to highlight the true benefits of vitamin D and prevent misconceptions.
Lack of Awareness
Doctors and researchers need to be aware of key studies demonstrating the benefits of vitamin D. Research should build on established knowledge to avoid wasting resources and slow progress. For instance, if researchers are unaware of previous studies showing the positive effects of high-dose vitamin D on autoimmune diseases, they may design redundant studies that do not build on this knowledge.
Enhancing awareness and understanding of past research can prevent duplication of efforts, promote more innovative studies, and accelerate progress in vitamin D research. This approach can lead to more effective public health recommendations and clinical practices, optimizing the use of vitamin D for health benefits.
Variability in Study Populations
Differences in the demographics and health status of study participants can significantly impact the outcomes of vitamin D research, leading to inconsistent and sometimes conflicting results. Factors such as age, baseline vitamin D levels, genetic background, and overall health status can all influence how individuals respond to vitamin D supplementation. For example, younger individuals might have different absorption and metabolism rates than older adults, and those with existing health conditions may respond differently than healthy participants.
Additionally, individuals with low baseline vitamin D levels may show more pronounced benefits from supplementation than those with sufficient levels. Standardizing study populations by controlling for these variables can help produce more reliable and comparable data, ensuring the results are more universally applicable.
Inadequate Funding and Support
The quality and reliability of vitamin D research should be improved by more funding. High-quality studies require significant resources for large, diverse participant groups, long-term follow-ups, and comprehensive data analysis. Limited funding can restrict the scope of research, leading to smaller sample sizes, shorter study durations, and less thorough investigations. Consequently, the findings from these underfunded studies may be less robust and more prone to variability.
Increased investment in vitamin D research would allow for more extensive and well-designed studies, providing clearer and more definitive insights into the benefits and optimal use of vitamin D. This could lead to better public health recommendations and more effective strategies for addressing vitamin D deficiency and its associated health risks.
Advantages and Strengths
Tackling these challenges necessitates the advancement of our research, the strengthening of nutrition education, and the widespread promotion of awareness regarding the most recent discoveries about vitamin D. In doing so, we can harness its full potential for human health.
Additionally, encouraging stronger collaboration among medical doctors, functional medicine practitioners, and medical scientists can refine research methodologies and data analysis, leading to superior patient care via appropriate vitamin D supplementation.
When designing and interpreting studies on vitamin D, several critical factors must be considered to ensure accurate and reliable results. These considerations are essential for understanding the true impact of vitamin D supplementation and avoiding methodological pitfalls that can lead to misleading conclusions. Below are the key considerations to keep in mind for conducting robust and meaningful vitamin D research.
Key Considerations for Vitamin D Studies
1. Dosage: Did the study subjects receive at least 3,000-10,000 IU per day? If not, the dosage likely needed to be improved to produce optimal physiological effects.
2. Duration: Was the study duration at least 6-9 months?
If not, the body stores of vitamin D likely were not replenished in time for a clinical effect.
3. Form of Vitamin D: Did the study use vitamin D3 (cholecalciferol) rather than ergocalciferol (fungally-derived)? Ergocalciferol is not a human nutrient; it is more toxic and less effective than cholecalciferol.
4. Product Validation: Was the product validated for potency?
If not, the intervention may have failed due to an inaccurately produced or falsely labeled product.
5. Serum Level Measurement: Were serum 25-OH-vitamin D levels measured? If not, the product potency and nutrient absorption were not ensured.
6. Optimal Serum Levels: Did serum 25-OH-vitamin D levels enter the optimal range at least 3-6 months before the study ended?
If not, the patients may have remained vitamin D deficient for the entire study.
7. Baseline Deficiency and Repletion: Were the patients vitamin D deficient at the start of the study and then aggressively supplemented? To properly study the effects of vitamin D, it’s important to start with participants who have low vitamin D levels and then give them enough vitamin D to replete to healthy optimal levels. The goal is to correct their deficiency and see how achieving optimal vitamin D levels affects their health.
8. Timing of Serum Testing: Vitamin D supplementation should be stopped 20-30 days before serum testing. This allows for an accurate assessment of tissue saturation, as 25-hydroxyvitamin D3 (calcidiol) has a half-life of 15 days. Testing too soon reflects absorption and hepatic conversion rather than tissue stores.
In other words, to get a true picture of how much vitamin D is stored in your body, you should stop taking supplements 20-30 days before the blood test. This waiting period helps ensure that the test reflects long-term vitamin D levels, not just recent intake.
9. Controlled Factors: Clinical trials need to control for factors that increase vitamin D status (e.g., sun exposure, fish oil, especially cod liver oil) and those that promote vitamin D deficiency (e.g., antiseizure drugs, cholestyramine).
It's important to aim for a healthy vitamin D level to lower parathyroid hormone (PTH) levels, which can be high when your body lacks enough calcium. According to a study by Heaney et al. (Am J Clin Nutr 2003 Jan), taking 10,000 IU (250 mcg) of vitamin D per day can help achieve this, resulting in a healthy vitamin D level of 80 ng/ml (200 nmol/L). These levels can also be naturally attained with sun exposure, so it's practical and beneficial to aim for a vitamin D level of 80 ng/ml (200 nmol/L).
2017 Vitamin D Supplementation Guidelines
In early 2017, vitamin D supplementation guidelines were published endorsing the following supplementation regimens:
• Neonates (younger than one month): 1,000 IU/day (25 mcg/day) for infants older than 1 month and toddlers older than 1 year: 2000-3000 IU/day (50-75 mcg/day)
• Children and adolescents aged 1 t o 18 years: 3000-5000 IU/day (75–125 mcg/day)
• Adults and the elderly: 7000–10,000 IU/day (175–250 mcg/day) or 50,000 IU/week (1250 mcg/week)
The authors also note that obese patients require up to 300% more vitamin D than individuals of normal weight. Additionally, doses of more than 10,000 IU/d had no adverse effects.
Obese patients need higher dosage of vitamin D than the recommended dose
It is generally accepted that a serum 25(OH)D concentration of up to 100 ng/mL (250 nmol/L) is safe for children and adults, except those who have a hypersensitivity to vitamin D. The Endocrine Society guidelines concluded that vitamin D toxicity is not only extremely rare but 25(OH)D concentration of at least 150 ng/mL (375 nmol/L) is required before there would be a risk of vitamin D toxicity.
Vitamin D Dosing: Basic Principles and a Brief Algorithm
Understanding Vitamin D Levels: Analyzing Optimal Ranges
In the algorithm above, vitamin D levels are categorized as follows:
• Less than 75 nmol/L: Below adequate, indicating a deficiency that requires supplementation
• 75-150 nmol/L: Considered normal, typically sufficient for most individuals
• 150-250 nmol/L: Requires monitoring for elevated blood calcium levels, as this range is approaching the higher end
• Greater than 250 nmol/L: Above the upper range, necessitating close monitoring for potential toxicity and especially high levels of blood calcium
While some studies have established these ranges as normal and safe, recent research suggests that the optimal range for vitamin D lies between 125-250 nmol/L. This range is believed to offer the most health benefits without significant risk of toxicity.
Additionally, even levels up to 375 nmol/L, though rarely seen as toxic, should be monitored to ensure safety and prevent hypercalcemia (high blood calcium levels). These findings indicate that while higher levels of vitamin D can be beneficial, it is crucial to monitor blood calcium levels to avoid potential adverse effects.
According to the 2011 clinical trial by Hollis et al., Vitamin D supplementation of 4,000 IU/day for pregnant women was safe and most effective in achieving sufficiency in all women and their neonates, regardless of race. A 2016 review supported the same dose and safety profile.
Vitamin D Supplementation during Pregnancy
Studies and Protocols
Support for a broad range of clinical applications for vitamin D supplementation comes from laboratory experiments, clinical trials, and epidemiologic surveys. Despite the imperfections of current data, we can still see significant benefits from vitamin D supplementation in a variety of human diseases, as briefly reviewed below.
Vitamin D deficiency in 4700 Hospital Patients
The following study concludes that long-term Vitamin D3 supplementation, even at high doses, is safe and beneficial for maintaining adequate Vitamin D levels and supporting overall health. Additionally, patients on long-term Vitamin D3 supplementation had higher levels, with a mean of 118.9 ng/ml (297.25 nmol/L), and no significant difference in serum calcium levels compared to those not supplemented. Additionally, those on Vitamin D3 had lower parathyroid hormone (PTH) levels, indicating improved calcium metabolism.
Vitamin D Toxicity
The evidence is clear that vitamin D toxicity is one of the rarest medical conditions and is typically due to intentional or inadvertent intake of extremely high doses of vitamin D (usually in the range of greater than 50,000-100,000 IU/d for months to years).
Vitamin D Is Not as Toxic as Was Once Thought: A Historical and an Up-to-Date Perspective
Vitamin D in Pregnancy and Autism Prevention
A small-scale study demonstrated that vitamin D supplementation during pregnancy (5000 IU/day) and early childhood (1000 IU/day) significantly reduced the incidence of autism in high-risk families, lowering the expected rate from 20% to 5%. This finding underscores the importance of adequate vitamin D levels during critical developmental periods.
Vitamin D in Children's Health
High-Dose Vitamin D and Autism
Recent studies have shown that high-dose vitamin D supplementation can improve core symptoms in autistic children. In open-label trials, approximately 75% of participants showed significant improvements with doses ranging from 300 IU/kg/day to 5000 IU/day. A randomized controlled trial (RCT) using similar dosing protocols confirmed these results, highlighting the potential of vitamin D in managing autism symptoms.
Vitamin D and autism, what's new?
Cardiovascular Disease
Cardiovascular disease fatalities tend to increase during winter, at higher latitudes, and at lower altitudes. These patterns align with the prevalence of vitamin D insufficiency.
The risk of heart attack is twice as high for those with vitamin D levels less than 34 ng/ml (85 nmol/L) than for those with vitamin D status above this level.
Patients with congestive heart failure were recently found to have markedly lower levels of vitamin D than controls.
Low vitamin D status: a contributing factor in the pathogenesis of congestive heart failure
Vitamin D deficiency as a cause of heart failure has been documented in numerous case reports including a small child.
Congestive heart failure caused by vitamin D deficiency
High Blood Pressure (Hypertension)
It is well-documented that blood pressure tends to be higher in winter than in summer, rises with increasing distance from the equator, and varies with skin pigmentation—patterns that align with the potential influence of vitamin D on blood pressure regulation.
Ultraviolet light may contribute to geographic and racial blood pressure differences
When patients with hypertension were treated with ultraviolet light three times a week for six weeks their vitamin D levels increased by 162%, and their blood pressure fell significantly.
Ultraviolet B and blood pressure
Even small amounts of oral cholecalciferol (800 IU) for eight weeks lowered both blood pressure and heart rate.
Type 2 Diabetes
Hypovitaminosis D, or vitamin D deficiency, is linked to insulin resistance and beta-cell dysfunction in both diabetics and seemingly healthy young adults. Adults with higher serum vitamin D levels exhibit significantly lower glucose levels at 60, 90, and 120 minutes post-meal, as well as markedly improved insulin sensitivity compared to those deficient in vitamin D.
Hypovitaminosis D is associated with insulin resistance and beta cell dysfunction
The authors noted that, compared with metformin, which improves
insulin sensitivity by 13%, higher vitamin D status correlated with a 60% improvement in insulin sensitivity. In a recent clinical trial using 1,332 IU/day for only 30 days in 10 women with type 2 diabetes, vitamin D supplementation was shown to improve insulin sensitivity by 21%.
Multiple Sclerosis (MS)
The autoimmune/inflammatory disease MS is notably rare in sunny equatorial regions. It becomes increasingly prevalent among people who live farther from the equator and who lack adequate sun exposure.
In a clinical trial with 10 MS patients, Goldberg, Fleming, and Picard prescribed daily supplementation with approximately 1,000 mg calcium, 600 mg magnesium, and 5,000 IU vitamin D (from 20 g cod liver oil) for up to two years and found a reduction in the number of exacerbations and an absence of adverse effects.
This is one of few human studies that employed sufficient daily doses of vitamin D (5,000 IU) and had enough duration (2 years).
The level of serum vitamin D affects the risk of developing MS and also modifies disease activity in MS patients.
Vitamin D and Multiple Sclerosis: A Comprehensive Review
Depression
Seasonal affective disorder (SAD) is a particular subtype of depression characterized by the onset or exacerbation of melancholia during winter months when bright light, sun exposure, and vitamin D levels are reduced. Recently, after one month, a dose of 100,000 IU of vitamin D was found superior to light therapy in treating SAD.
Vitamin D vs broad spectrum phototherapy in the treatment of seasonal affective disorder
Similarly, in a study involving 44 subjects, supplementation with 400 or 800 IU per day was found to significantly improve mood within five days of supplementation. Can you imagine if they would have used 4,000 IU or above!?
Vitamin D3 enhances mood in healthy subjects during winter
Epilepsy
Vitamin D deficiency is common in patients with epilepsy on antiepileptic drugs. Monitoring of vitamin D should be considered as part of the routine management of patients with epilepsy.
Low Vitamin D Levels Are Common in Patients with Epilepsy
Loss of seizure control in patients stabilized on antiepileptic drugs (AEDs) is an indication to check the patient's vitamin D and calcium status. Proper treatment of this complication is vitamin D and calcium supplementation. Prophylactic supplementation with vitamin D is necessary in institutionalized patients treated with AEDs.
Loss of seizure control due to anticonvulsant-induced hypocalcemia
Conversely, supplementation with 4,000–16,000 IU per day of vitamin D2 was shown to significantly reduce seizure frequency in a placebo-controlled pilot study. Lower doses may have been used if vitamin D3 had been used instead of the inferior D2.
Anticonvulsant action of vitamin D in epileptic patients-a controlled pilot study
Migraine Headaches
Twenty-two studies looked at how serum vitamin D levels and headaches are related. Eight of these studies also checked if taking vitamin D supplements affects headaches. Of the 22 studies, 18 found a link between low vitamin D levels and headaches, with the strongest connection seen in people with migraines. Current research indicates that taking vitamin D supplements may lower the frequency of headaches for some patients, particularly those with migraines and vitamin D deficiency.
The Role of Vitamin D in Primary Headache–from Potential Mechanism to Treatment
Calcium plays a role in maintaining vascular tone and coagulation, which is altered in patients with migraines. Thys-Jacobs reported two cases showing a reduction in frequency, duration, and severity of menstrual migraine attacks following daily supplementation with 1,200 mg of calcium and 1,200–1,600 IU of vitamin D in women with vitamin D deficiency.
Vitamin D and calcium in menstrual migraine
Musculoskeletal Pain
Patients with non-traumatic, persistent musculoskeletal pain show an impressively high prevalence of vitamin D deficiency. Plotnikoff and Quigley showed that 93% of their 150 patients with persistent, nonspecific musculoskeletal pain were deficient in vitamin D.
Prevalence of severe hypovitaminosis D in patients with persistent, nonspecific musculoskeletal pain
Masood et al. found a high prevalence of vitamin D deficiency in children with limb pain. Vitamin D supplementation alleviated pain within three months.
Al Faraj and Al Mutairi found vitamin D deficiency in 83% of their 299 patients with low-back pain. Supplementation with 5,000–10,000 IU of vitamin D daily led to pain reduction in nearly 100% of patients after three months.
Vitamin D deficiency and chronic low back pain
Critical Illness and Autoimmune/Inflammatory Conditions
Deficiency of vitamin D is common among patients with inflammatory and autoimmune disorders and those with prolonged critical illness. In addition to the previously mentioned epidemic of vitamin D deficiency in patients with MS, we also see evidence of vitamin D insufficiency in a large percentage of patients with the following:
• Grave’s Disease: High prevalence of vitamin D deficiency in Japanese female patients with Graves' disease
• Ankylosing Spondylitis: Patients with ankylosing spondylitis may have extremely low levels of vitamin D
• Systemic Lupus Erythematosus (SLE) and Fibromyalgia: Vitamin D levels in women with systemic lupus erythematosus and fibromyalgia
• Rheumatoid Arthritis: vitamin D deficiency is highly prevalent in patients with RA, and that vitamin D deficiency may be linked to disease severity in RA
Cancer Prevention and Treatment
Henry Lancaster Apperly was a researcher known for his pioneering work in the early 20th century that explored the relationship between sunlight exposure and cancer mortality. His most notable contribution was documenting the inverse relationship between sunlight exposure and cancer death rates in a paper published in 1941. This study laid the groundwork for later research into the role of vitamin D, synthesized in the skin through exposure to ultraviolet (UV) rays from sunlight, in cancer prevention and overall health.
Does sunlight have a beneficial influence on certain cancers?
Vitamin D helps fight cancer by stopping cancer cells from growing and causing them to die. It affects how certain receptors and enzymes work in our bodies. Some research also shows that synthetic versions of vitamin D might help treat cancer.
Influence of vitamin D on cancer risk and treatment
Not getting enough sunlight, and therefore not enough vitamin D, increases the risk of dying from various cancers, including breast, colon, ovary, prostate, bladder, esophagus, kidney, lung, pancreas, rectum, stomach, uterus, and non-Hodgkin lymphoma. He suggests that getting enough sunlight and taking vitamin D supplements could save over 23,000 American lives each year by reducing cancer deaths.
Recent studies on vitamin D have shown its many health benefits. However, new research indicates that adults need a minimum of 3,000–5,000 IU of vitamin D daily, and it takes 3-4 months of daily supplementation for levels to stabilize. This means that studies using lower doses and shorter periods likely underestimated vitamin D's effectiveness.
As we conclude our comprehensive exploration of the importance of vitamin D, it is evident that this essential nutrient/prohormone plays a critical role in maintaining overall health and well-being. From supporting bone health and immune function to potentially reducing the risk of chronic diseases such as diabetes, cardiovascular diseases, and certain cancers, vitamin D's benefits are far-reaching.
In Part 1, we delved into vitamin D's fundamental benefits and crucial role in various physiological functions. We highlighted the importance of maintaining adequate vitamin D levels for optimal health.
In Part 2, we examined the essential cofactors that enhance vitamin D's efficacy, discussed the potential depletion of other vitamins and minerals, and uncovered the "Calcium Paradox." We emphasized the significance of balanced nutrient intake to maximize vitamin D's benefits and maintain overall health.
In this final installment, Part 3, we addressed the challenges and misconceptions in vitamin D research. We discussed the need for specialized training among physicians and researchers, proper dosing and study durations, and the impact of variability in study populations. We also reviewed the 2017 Vitamin D Supplementation Guidelines and highlighted numerous studies supporting vitamin D's broad clinical applications.
Together, these insights emphasize the importance of vitamin D in our lives and the need for ongoing research and education to harness its potential fully. By staying informed and proactive about our vitamin D levels, we can take meaningful steps toward improving our health and preventing various conditions.
Thank you for joining me on this long, three-part journey through the essential world of vitamin D. I hope this series has provided valuable information and encouraged you to prioritize your vitamin D levels for a healthier, more resilient future. 😊