Vitamin D, or the sunshine vitamin, has become a mainstay in both mainstream and alternative healthcare routines. It is touted as a "must-have" in nearly all supplement routines for those seeking relief from anything from autoimmune conditions to cardiac and neurological disorders.
With countless studies, elite-level physician and board-certified endorsements, its difficult to deny Vitamin D's' health benefits.
I've spent a good amount of time researching the physiology and nutrient interactions underlying the grandiose health claims behind this vitamin panacea. And there's something fishy about it to me... I've been reluctant to expand on it. Partially because I didn't quite have the words to properly convey the incongruence I was seeing, and partly because I thought it may just be my contrarian nature looking for reasons not to trust the mainstream.
But let's elaborate. Maybe putting this into words can help show you what I'm seeing and why it leaves me still uncertain after all this time.
The rise of Vitamin D as the cure-all that we all seem to be missing is rife with money trails, private interests and lackluster science.
The Lifecycle of Vitamin D
Vitamin D gets its sunny affiliation because our body is able to naturally produce it using energy from the sun to convert a certain form of cholesterol in our skin. Let's look at the typical path of Vitamin D from beginning to end:
Sunlight Exposure: The primary source of vitamin D for most people is sunlight. When the skin is exposed to ultraviolet B (UVB) radiation from the sun, a form of cholesterol in the skin is converted into vitamin D3 (cholecalciferol).
Dietary Sources: Vitamin D can also be obtained from certain foods, including fatty fish (such as salmon, mackerel, and sardines), fortified foods (such as milk, orange juice, and cereals), and supplements.
Absorption in the Intestines: Once it is synthesized in the skin or ingested from food or supplements, vitamin D is absorbed in the small intestine, primarily in the upper part known as the duodenum.
Transport in the Blood: Vitamin D is transported in the bloodstream bound to a specific carrier protein called vitamin D-binding protein (DBP) to the liver for hydroxylation.
First Hydroxylation in the Liver: In the liver, vitamin D is converted to 25-hydroxyvitamin D [25(OH)D], also known as calcidiol, through a hydroxylation process mediated by the enzyme 25-hydroxylase. This is the major circulating form of vitamin D and is used to assess vitamin D status in the body.
Second Hydroxylation in the Kidneys: The next step in the activation of vitamin D occurs in the kidneys, where 25(OH)D is converted to its active form, 1,25-dihydroxyvitamin D [1,25(OH)2D], also known as calcitriol, by the enzyme 1-alpha-hydroxylase. This active form of vitamin D is responsible for the biological effects of vitamin D in the body.
Utilization in Target Tissues: Once activated, vitamin D acts on target tissues, such as the intestines, bones, and immune cells, by binding to vitamin D receptors (VDRs). This interaction regulates the expression of genes involved in calcium absorption, bone metabolism, and immune function.
Regulation by Parathyroid Hormone (PTH) and Calcium: The activation of vitamin D in the kidneys is tightly regulated by parathyroid hormone (PTH) and calcium levels in the blood. Low calcium levels stimulate PTH release, which, in turn, stimulates the kidneys to produce more 1,25(OH)2D to enhance calcium absorption in the intestines.
Compounding Factors
No substrate in the body acts in isolation. Everything is a part of a multi-faceted system of checks and balances actively and passively regulating multiple systems up and downstream. For Vitamin D, these include enzymes, cell receptors and other nutrients (I've highlighted some in orange from the D pathway above).
So let's take inventory: Cholesterol + Sunlight
-> Cholecalciferol (the D3 we supplement)
-> Absorbed in the small intestine
-> Delivered to the LIVER via Vitamin D Binding Protein (DBP)
-> Converted via 25-hydroxylase to Calcidiol (25(OH)D) (What shows up on Vit D tests)
-> Delivered to the KIDNEYS
-> Converted by 1-alpha-hydroxylase to Calcitriol (1,25(OH)2D (The ACTIVE form of D)
-> Calcitriol binds to target tissues via Vitamin D Receptor (VDR)
Health effects observed
Seeing and understanding this cascade is paramount to asking better questions when it comes to the ties between Vitamin D and our health outcomes.
Our healthcare system operates in a linear fashion that tends to minimize the circuitous and inter-related aspects of our bodily systems. With Vitamin D (and most all blood tests), we treat deficiencies as isolated incidents.
IE Low in Vitamin D? Take more Vitamin D.
But this cascade illustrates that a Vitamin D test result and the resulting plan of action to influence the availability of calcitriol involves much more than just Vitamin D.
When we supplement Vitamin D, are we accounting for the quantity and efficacy of the cofactors that properly convert cholecalciferol?
What about the health of the organs responsible for hosting these reactions? Is someone testing low for vitamin D actually low in vitamin D, or are their intestines, kidneys, or liver struggling to keep up?
For someone with a defective vitamin D processing capacity, does supplementing make sense?
None of the most commonly available vitamin D tests are accounting for these compounding variables. In fact, its possible to have 25(OH)D levels test normal but the body is critically low in 1,25(OH)D2. So what good is a test? And what about supplementing cholecalciferol (D3) addresses the actual issue?
Coming to the conclusion of being low in 25(OH)D meaning you just need to take more cholecalciferol requires that you make the assumption that every other factor influencing vitamin's D utilization is sufficient.
That would mean that:
The cholesterol in your skin is adequate and properly equipped to convert to cholecalciferol
Your small intestine is able to absorb the cholecalciferol
You have enough healthy and functional DBP to get the D from your skin to your liver
Your liver is healthy enough to properly source 25-hydroxylase to convert cholecalciferol to calcidiol
Your kidneys are healthy enough to adequately source and process 1-alpha-hydroxlyase's conversion of calcidiol to calcitriol
Vitamin D receptors in all the target tissues is in a proper state to receive the circulating calcitriol
That is A LOT that has to go right. That is A LOT that we have taken for granted when it comes to supplementing a form of vitamin D that is at the BEGINNING of the entire cascade.
This is like assuming that a bakery will have no problem filling their shelves with pastries just because they got a huge flour delivery. What about the ovens? The butter? The sugar? The bakers??
And consider the altered state of health that most people being prescribed vitamin D are in. From depression to diabetes, heart disease to Alzheimer's, can we say with any degree of confidence that their endocrine system, digestive system and liver/kidney/GI integrity is in a position to function optimally?
Big Science has successfully oversimplified and minimized a multi-variable equation into a single, financially convenient pill-for-your-ill output. Follow the MONEY Dr. Michael Holick is a name ubiquitous with the commercial rise in popularity of Vitamin D and its health effects over the past three decades. He has lead several studies and authored numerous papers describing the sunshine vitamin as a cure-all in today's healthscape. (7,8,9)
Early In 2011 the National Academy of Medicine, commissioned by the US and Canadian governments, issued over 1,000 pages on the current state of vitamin D deficiency in America (10, the report brief). They concluded that the great majority of Americans receive adequate vitamin D via diet and sun exposure. They detailed the dosing of both vitamin D and calcium to optimize bone resorption while noting documented health risks of both over and underconsumption.
That very same year, the Endocrine Society, for whom Holick oversees its publications, authored a paper taking the opposite stance (11). This paper stated "vitamin D deficiency is very common in all age groups” and advocated a huge expansion of vitamin D testing, targeting more than half the United States population.
Not so coincidentally, the Endocrine Society is the professional group whose guidelines are widely used by hospitals, physicians and commercial labs nationwide.
With this new, complete reversal of opinion on Vitamin D, the nutraceutical market responded accordingly. The global vitamin D market was valued at $1.1 billion dollars in 2020 and is expected to grow at a nearly 10% rate for the next decade.
And it wasn't just the supplement market that benefitted. Unlike the initial 2011 study, which concluded that patients have sufficient vitamin D when their blood levels are at or above 20 nanograms per milliliter, the Endocrine Society said vitamin D levels need to be much higher — at least 30 nanograms per milliliter. Many commercial labs, including Quest and LabCorp, adopted the higher standard.
Overnight, about 80% of Americans found themselves now vitamin D deficient.
As luck would have it, Dr. Holick just so happens to be a paid consultant by Quest Diagnostics. Quest is the leading provider of commercial vitamin D tests.
Holick also has significant financial connections to the pharmaceutical industry. Between 2013 and 2017, he received almost $163,000 from pharmaceutical companies, as reported by Medicare's Open Payments database (12). These companies included Sanofi-Aventis, a manufacturer of vitamin D supplements; Shire, which produces drugs for hormonal disorders often used alongside vitamin D; Amgen, a maker of osteoporosis treatments; and Roche Diagnostics and Quidel Corp., both of which manufacture vitamin D tests.
This is a HUGE red flag for me. A man who profits from the funneling of people into vitamin D testing and supplementation is promptly put into a position to create new industry standards that conveniently fit his narrative and financial interests.
OK, you may be thinking, but what if it actually works? Let the man be paid for his good work if vitamin D helps the way its marketed to.
The Underwhelming Reports on Vitamin D
While the mainstream, wellness-industrial complex makes it difficult to make the case against vitamin D, it's worth looking into the emerging professional consensus on its efficacy.
The results remain inconclusive. Common defenses of the results include themes of incomplete inclusion criteria and a lack of agreement on what exactly constitutes a deficiency. But if D were really the panacea it's sold as, the results would be undeniable.
The most compelling pro-Vitamin D research is related to bone health. Because of D's strong ties to proper calcium balance, it would make sense that more D would improve mineralization of bone. However, intermittent or daily administration of standard doses of vitamin D alone has not been associated with a reduced risk or prevention of fracture among adults older than 50 with no pre-existing deficiencies or illnesses (4).
For chronic illnesses like cancer, diabetes and heart disease, supplementation seems to have no meaningful effect (1,2,3).
With so much hype, much of the literature typically ends it's discussion on the potential for Vitamin D with statements like this (emphasis added):
In summary, it is necessary to recognize that our knowledge of the real relationships between vitamin D and the pathologies we have reported is still very limited, and there is no strong experimental evidence that confirms this association. Despite the above, currently, we do not have a definite cut-off level at which vitamin D could be the cause of several diseases such as those described in this review, and, importantly, we do not have any evidence-based data showing that the prescription of vitamin D (at different dosages) could improve the course of these diseases. Further epidemiological and mechanistic studies are necessary in order to ascertain the real role of hypovitaminosis in causing the reported diseases and to confirm the positive role of vitamin supplementation in prophylaxis and therapy. (5)
The following excerpts are all sourced from the Office of Dietary Supplements, an extension of the National Institute of Health (6):
Regarding Vitamin D's ties to health outcomes:
The FNB (Food and Nutrition Board) committee that established DRIs for vitamin D found that the evidence was inadequate or too contradictory to conclude that the vitamin had any effect on a long list of potential health outcomes (e.g., on resistance to chronic diseases or functional measures), except for measures related to bone health. Similarly, in a review of data from nearly 250 studies published between 2009 and 2013, the Agency for Healthcare Research and Quality concluded that no relationship could be firmly established between vitamin D and health outcomes other than bone health.
Regarding Vitamin D's clinical trial evidence on bone health in older adults :
Among postmenopausal women and older men, many clinical trials have shown that supplements of both vitamin D and calcium result in small increases in bone mineral density throughout the skeleton. They also help reduce fracture rates in institutionalized older people. However, the evidence on the impact of vitamin D and calcium supplements on fractures in community-dwelling individuals is inconsistent.
Regarding Vitamin D and Cancer outcomes:
The USPSTF stated that, due to insufficient evidence, it was unable to assess the balance of benefits and harms of supplemental vitamin D to prevent cancer. Taken together, studies to date do not indicate that vitamin D with or without calcium supplementation reduces the incidence of cancer, but adequate or higher 25(OH)D levels might reduce cancer mortality rates.
Regarding Vitamin D and Cardiovascular Disease (CVD):
Overall, clinical trials show that vitamin D supplementation does not reduce CVD risk, even for people with low 25(OH)D status (below 20 nmol/L [12 ng/mL]) at baseline.
Regarding Vitamin D and Depression:
Overall, clinical trials did not find that vitamin D supplements helped prevent or treat depressive symptoms or mild depression, especially in middle-age to older adults who were not taking prescription antidepressants.
Regarding Vitamin D and Diabetes:
Clinical trials to date provide little evidence that vitamin D supplementation helps maintain glucose homeostasis, reduces the risk of progression from prediabetes to type 2 diabetes, or helps manage the disease, particularly in vitamin D-replete individuals.
Regarding Vitamin D and Weight Loss:
Overall, the available research suggests that consuming higher amounts of vitamin D or taking vitamin D supplements does not promote weight loss.
This is why vitamin D makes me uneasy.
The biochemistry of vitamin D suggests significantly more complicating factors in its metabolism and proper utilization than is recognized among the healthcare professionals. Little is being to done to address the factors directly influencing Vitamin D's impact.
Dr. Holick and his suspicious profit-fed advocacy of vitamin D as a major health player.
There is next to no consensus in the research and medical community on the benefits and efficacy of supplementing vitamin D on major health outcomes.
When you take into account all of these unnerving details and combine them with the fact that it's become heresy to question any one of the claims being made FOR vitamin D, thats a recipe for hesitation on my part.
And I'm aware of my own biases:
The same arguments for the integrity of the pro-vitamin studies can be made for those questioning vitamin D.
The sources for vitamin D greatly outweigh those that speak against it.
A business affiliation does not necessarily disqualify the merit of a doctor or researcher's work.
Improvements to dosing, sourcing and industry standards of measurement may bring positive benefits to the surface.
But my questions and concerns still stand. Every person I've ever brought them up to had no answer. Most of them had never heard of the points I mentioned.
I think it worthy to make both sides of the coin known and let the people decide for themselves.
And let me be very clear. I completely understand the importance of vitamin D. This article is not to dispute the importance of the hormone/vitamin itself. It's documented health effects and critical role in human health is REAL.
But how we go about getting it and how we prepare our body to properly source, absorb and use it, deserves a second look.
REFERENCES AND CITATIONS