Optimizing Vitamin D Supplementation: Latest Discoveries and Synergistic Effects

In our previous post, we covered the basics of vitamin D. Now, we’ll explore how to effectively supplement vitamin D based on recent findings from the past few years, as sun exposure and dietary intake alone may not suffice.

Some readers have shared their experiences, revealing that even when their vitamin D levels tested below the “deficiency” threshold (<20ng/ml), healthcare providers didn’t recommend supplementation. For those advised to supplement, they were often told to take daily doses of 400IU – 800IU, but found their vitamin D levels didn’t increase significantly, if at all, after several months of supplementation.

How to Correct Vitamin D Deficiency?

When vitamin D deficiency is detected, how should it be supplemented? According to the clinical guidelines of the Endocrine Society [1]:

For children and adolescents aged 1 to 18 years:

• A daily dose of 2000 IU of D2/D3 or a weekly injection of 50,000 IU of vitamin D2 for 6 consecutive weeks can be given.
• Once the level reaches 30ng/ml, the maintenance dose should be adjusted to 600-1000 IU per day.

For adults with vitamin D deficiency:

• A daily dose of 6000 IU of D2/D3 or a weekly injection of 50,000 IU of vitamin D2 can be given for 8 consecutive weeks.
• Once the level reaches 30ng/ml, the maintenance dose should be adjusted to 1500-2000 IU per day.

The maintenance dose may need to be continued for several years [2]. A retrospective study conducted by Boston University on clinical patients found that in many cases, maintenance doses were required for up to 6 years [3].

Vitamin D Supplementation Duration

The half-life of vitamin D doesn’t provide significant guidance as it can be stored in adipose tissue for the medium to long term. Studies showed varying half-life results, ranging from 74 to 82 days. Additionally, inflammation can shorten the half-life, making it unpredictable. Ongoing inflammation in vitamin D-deficient individuals may continuously consume vitamin D.

In a study, a single injection of 600,000 IU of vitamin D increased levels without side effects, with a half-life of 74 days [4]. Another study with a single injection of 100,000 IU followed by daily 4800 IU supplementation showed a half-life of 82 days over two months. Both studies had similar results, lasting 2 to 3 months [5].

Inflammation can impact vitamin D half-life. In healthy individuals, it’s around 80 days, but in severe inflammation, it can drop to 10 days [6]. This varies among individuals, making it hard to determine one’s vitamin D half-life. Vitamin D deficiency and inflammation may constantly consume vitamin D.

Regular blood tests are the most meaningful way to guide vitamin D supplementation. Levels below 30ng/ml indicate insufficiency to deficiency, requiring higher supplement doses. After 8 weeks, a follow-up test helps determine the ideal level. Once achieved, the daily dose can be reduced to a maintenance dose. Checking vitamin D levels through blood tests is crucial.

Expert guidelines suggest testing “high-risk” individuals with deficiencies, but this may exclude those at risk, like pregnant women and the elderly. Around 40% of the population with potential deficiencies may not be tested, leading to disagreement with experts.

Ideal Vitamin D Levels

There is no consensus on vitamin D deficiency or optimal levels among professionals.

A study published in June 2020 [7] suggests that vitamin D levels between 50 and 70ng/ml may be ideal for chronic diseases like diabetes. Another clinical study in 2018 [8] found that vitamin D levels of 51ng/ml could potentially reduce premature ejaculation in lifelong premature ejaculation patients.

A study from the University of Alberta in Canada challenges the current RDA of 600 IU for vitamin D intake in the United States and Canada, as it may not ensure sufficient vitamin D levels [9].

A global initiative, “D*Action,” recommends maintaining levels between 40-60ng/ml for disease prevention, backed by 30 renowned universities and 48 endocrinology experts. Achieving these levels is vital for overall health [10].

Vitamin D Interacts Synergistically with Other Micronutrients

Maintaining adequate magnesium intake during vitamin D supplementation is crucial, as high-dose vitamin D supplements can deplete magnesium levels  [11].

A study from Vanderbilt University found that sufficient dietary magnesium intake may reduce the risk of vitamin D deficiency and insufficiency [12].

Magnesium supplementation can also raise vitamin D levels. A double-blind clinical study from Spain showed that daily magnesium supplementation significantly increased vitamin D levels in participants [13].

Vitamin K has a synergistic effect with vitamin D in regulating blood calcium and bone health. While vitamin D increases calcium absorption, vitamin K can reduce calcium accumulation in soft tissues, enhance calcium absorption in bones, and reduce the risk of high blood calcium caused by high-dose vitamin D [14].

Matrix Gla protein (MGP) is an inhibitor of vascular and cartilage calcification, and active vitamin D increases MGP expression. However, vitamin K is an essential cofactor for the carboxylation of MGP, which enables the production of active MGP and achieves the effect of softening blood vessels or reducing soft tissue calcification. An intervention study of 181 middle-aged and elderly women found that when vitamin D and vitamin K were supplemented together, the elasticity of blood vessels was not affected [15].

Some studies have suggested that using vitamin A or K together with vitamin D can reduce the risk of vitamin D toxicity and provide protection to the body. The most important food sources of vitamin D, such as liver and fish liver oil, also contain vitamin A. Animal experiments have also shown that rats injected with ultra high doses of vitamin D, when given oral vitamin A or vitamin K2, do not experience vitamin D toxicity [16].

Vitamin D, magnesium, vitamin K, and vitamin A form an “alliance” in regulating the immune system and work synergistically. Supplementing magnesium while taking vitamin D may provide more significant benefits.

Bolus is Bogus

Recent evidence suggests that taking vitamin D daily or weekly is better for improving health than taking large bolus doses.

A study analyzing 25 trials found that daily or weekly vitamin D doses provided protective effects against respiratory infections, while bolus doses did not. Bolus dosing may not prevent acute respiratory infections effectively and could lead to fluctuations in vitamin D levels [17].

Another review showed that daily or weekly dosing of vitamin D is more effective for improving various health outcomes, including respiratory infections, COVID-19, rickets, falls, fractures, cancer, and mortality [18].

Bolus dosing might disrupt the synthesis and degradation of active vitamin D and trigger countervailing effects. It could also affect vitamin D receptors in the intestine and the composition of the microbiota [19].

To be safe, it’s recommended to split bolus doses into smaller daily amounts taken orally.

Summary

Correcting Vitamin D Deficiency: For children and adolescents, a daily dose of 2000 IU of D2/D3 or a weekly injection of 50,000 IU for 6 weeks is recommended. Adults can take 6000 IU daily or receive a weekly injection for 8 weeks. Maintenance doses of 600-1000 IU or 1500-2000 IU per day are advised.

Supplementation Duration: Vitamin D half-life varies, and inflammation can affect it. Regular blood tests are crucial to guide supplementation. Bolus doses may be less effective than daily or weekly dosing.

Ideal Vitamin D Levels: No consensus exists on optimal levels. Studies suggest maintaining levels between 40-70ng/ml for disease prevention.

Vitamin D Synergy: Vitamin D interacts with magnesium and vitamin K. Adequate magnesium intake is crucial during vitamin D supplementation. Vitamin K enhances bone health by reducing calcium accumulation in soft tissues.

Bolus is Bogus: Daily or weekly vitamin D supplementation is superior to large bolus doses. Daily or weekly dosing shows better outcomes in preventing respiratory infections, COVID-19, rickets, and more. Bolus doses may disrupt vitamin D regulation and the microbiota.