Sometimes it takes a pandemic to recognize a hidden gem.
We can add Vitamin D to that list now.
We're not talking about avoiding rickets and bone wasting...those issues are largely relegated to the distant past in most countries.
Our interest is broader...into general health and well-being.
- Mental health
- Immune response (with a focus on inflammation)
- Brain function
Sure, bone health is important as Vitamin D controls calcium absorption back into the bones but serotonin is so much more relevant now.
It's just the master regulator of human behavior and Vitamin D is critical there.
Vitamin D's downstream effects on magnesium and acetylcholine are nothing short of revolutionary as we'll find out below.
That's your calming mineral and your rest and digest + focus neurotransmitter.
So anxiety and dementia.
Let's get to it with a quick introduction (to be expanded later) on how people with darker skin are especially affected (with no real mention in the media).
Roughly half of the population is deficient and that number goes up to 80% for African Americans.
Here are the topics we'll cover:
- A quick introduction to Vitamin D
- The basic role of VItamin D in the body
- Vitamin D and neurotransmitters
- Vitamin D and mental health
- Vitamin D and inflammation and immune response (autoimmune!!)
- Vitamin D and the gut (microbiome)
- Vitamin D and neurogenesis (brain repair)
- Vitamin D and magnesium
- Vitamin D and sleep
- Vitamin D and weight
- Vitamin D and brain function
- Vitamin D and skin
- Vitamin D and cancer
Let's get started.
A quick introduction to Vitamin D
Vitamin D isn't really a vitamin after all.
Technically, it's a steroid. A hormone since its active form is made in the liver and kidney (2 step process).
Food is a very poor source with fatty fish and mushrooms being reliable sources.
Most of our vitamin D comes from the sun!
Our skin converts UV light into the precursor of Vitamin D and that's our main source.
With less exposure to sunlight (indoors, sunblock, etc.), Vitamin D deficiency is nothing short of a pandemic.
It's estimated that 40% of the world's population is deficient. This number roughly doubles based on skin color since melanin (what makes skin darker) blocks vitamin D conversion from UV light.
Goodness! Think of the impacts of that. If you're getting plenty of sunlight (tropics), its fine but what about if you're in New York or further north?
To understand why D is so important, we have to figure out its role in the body first.
Let's go there now!
The basic role of VItamin D in the body
D's starring role is that of managing calcium (and phosphorus).
The impact of this is obvious in terms of bone density but calcium plays a much more basic role in the body.
Calcium is the currency (or a currency) of cellular activity!
Many essential, critical really, pathways use calcium as a way to manage activity.
The neurotransmitters which govern what we feel and how our brains work to use these "calcium channels" to turn up or down activity within neurons or between them.
It would be like if you suddenly dropped the amount of currency in the world by half.
The entire economy would shut down.
Vitamin D resembles a slow loss rather than a sudden disappearance.
Let's look at that piece.
Vitamin D deficiency - age, skin color, and calcium
The importance of sufficient levels of D is now being understood:
Epidemiologic evidence indicates an association between low levels of vitamin D and diseases associated with aging such as cognitive decline, depression, osteoporosis, cardiovascular disease, hypertension, type 2 diabetes, and cancer.
There are known causes for D deficiency.
First, age which is a big factor:
Production of 1,25(OH)2D is reduced by 50% as a result of an age-related decline in renal function,
Interestingly, a drop in calcium comes first:
Aging also causes a decrease in calcium absorption that precedes the decrease in 1,25(OH)2D by 10 to 15 years.
The entire pathway of D (absorption, conversion, VDR gene expression, etc.) goes down with age.
You could argue that D is one of the first chips to fall on the way to aging (along with pregnenolone).
Then there's skin color.
The darker the pigmentation of the skin, the less absorption of vitamin D.
Unfortunately, our biology is a few million years old.
If you're in intense sunshine, the body has a protective measure from too much UV radiation and subsequently, too much Vitamin D (which can be dangerous).
The problem is when you (or your ancestors) move to a part of the world where UV light is greatly reduced.
The Vitamin D deficiency rate for African Americans is roughly 80%! For Latin Americans, 60-70%.
When you read below, you'll understand just how crucial this is!
There are many other factors affecting Vitamin D levels but let's get to the heart of why we're here.
Let's turn our attention to our neurotransmitters specifically now since they figure directly into mental health and proper brain function.
Vitamin D and neurotransmitters
So...if Vitamin D manages calcium and this is the main currency of powerful players in our brain, is there an impact there directly?
Let's run through just the big players:
- Serotonin - our master brain regulator of all human behavior (and the gut by the way)
- Dopamine - our reward circuit controller which serotonin governs
- Glutamate and GABA - the gas and brake pedals of brain activity
- Norepinephrine - the getup and go chemical for focus and fight of flight (adrenaline is downstream)
- Acetylcholine - both focus, learning AND rest and digest control (the vagus nerve)
The list above interact with each other for a carefully orchestrated dance that, when operating correctly, make us think and feel well.
So...what about Vitamin D?
Let's start with serotonin since its key to depression, anxiety, and just about every mental health issue (not to mention just plain mood).
Vitamin D and serotonin
First, the technical...we'll translate, promise:
Optimal vitamin D spurs serotonin: 1,25-dihydroxyvitamin D represses serotonin reuptake transport (SERT) and degradation (MAO-A) gene expression in cultured rat serotonergic neuronal cell lines
Goodness. Vitamin D boosts the creation (tryptophan to serotonin), the availability (SERT), and reduces the breakdown (MAO) of serotonin!!
Keep in mind that SSRI's are aiming to just do one of these things (availability) and they build a tolerance.
What you just read there is revolutionary. Serotonin is THAT important to brain function and mood.
It's imprint is on almost every mental health issue since it works like a master regulator for the other players.
Remember how we said Vitamin D is a steroid?
You have to disavow any preconceptions of that word from bodybuilding, etc.
Steroids are very important actors in the body and brain as growth agents in a delicate battle against atrophy.
Atrophy from the damages of the day: hyperactive immune response (autoimmune, etc.), inflammation, stress hormones, etc.
There's a daily fight against the pathways that break us down and those that build us up and steroids figure into the second half.
We'll see Vitamin D's impact below in this capacity for neurogenesis where serotonin figures into prominently.
Learn more about serotonin here:
- CBD versus SSRIs
- CBD and the pathway of serotonin
- How do SSRIs really work
- Is tryptophan a social stress buffer
Our primary focus is on CBD but you can learn all about the same pathways via those articles as Vitamin D has a direct, stimulating effect.
And to think half the population is deficient and absorption decreases as we get older.
Serotonin is a manager of dopamine...let's head there now.
Vitamin D and dopamine
A study looked at vitamin D deficiency in mothers and their children and found the following:
There was also some evidence of increased lateral ventricle volume and altered neural expression of genes involved in dopamine and glucocorticoid-related pathways suggesting autism and schizophrenic-like disorders
Dopamine is very important for brain development with powerful ties to serious developmental mental health issues like schizophrenia, bipolar, and autism.
Where dopamine really makes its entrance is with addiction (see CBD and addiction).
In fact, for a substance to be addictive, it needs to stoke dopamine activity as a reward "learning" agent.
There's fascinating research on how Vitamin D can protect dopamine neurons following drug use.
For example with meth:
Vitamin D-treated animals showed significant attenuated methamphetamine-induced reductions in dopamine and metabolites when compared to control, indicating that vitamin D provides protection for the dopaminergic system against the depleting effects of methamphetamine.
Essentially, meth will exhaust dopamine levels (eats it up) and D would protect these neurons from resulting effects.
This appears to go down to the genetic level:
vitamin D activates genes that regulate the immune system and release neurotransmitters (e.g., dopamine, serotonin)
Again, remember...it's a steroid...it boosts activity in critical pathways.
What about the primary excitatory and inhibitory chemicals?
Vitamin D and GABA/Glutamate balance
Our brain's are in a constant state of balancing multiple acts.
The biggest, center stage really is between GABA and glutamate.
They manage "activity" levels at every other pathway. Serotonin, dopamine...you name it.
Too much glutamate is highly destructive to brain tissue (see CBD and glutamate). Too little GABA has this same effect.
Again, a very important balance with multiple checks on glutamate's wayward tendencies.
GABA is the target for benzos (like Valium and Xanax) so it has a generally calming, downshifting effect. The sleep aids usually hit GABA as well.
So...what about Vitamin D?
Looks what happens when it's deficient:
Vitamin D deficiency induces the excitation/inhibition brain imbalance and the proinflammatory shift
The study is technical but it's directly driven by GABA and glutamate levels and inflammation is a result (remember...too much glutamate is like redlining a car engine but with your brain cells!).
Let's now turn to our autonomic nervous system, the player behind the curtain in charge of fight or flight and rest and digest.
First up, norepinephrine (and it's breakdown chemical, adrenaline!).
There's a cascade here with norepinephrine being made from dopamine so we expect actions with vitamin D just based on that.
You want enough norepinephrine to feel engaged...enthused but not enough to where you're coming out of your skin.
Vitamin D deficiency resulted in a significant decrease in endogenous norepinephrine.
In fact, Vitamin D controls (up and down) the elements of the HPA axis which manages how we respond to stress:
Vitamin D modulates the hypothalamic-pituitary-adrenal axis, regulating adrenalin, noradrenaline and dopamine production through VDRs in the adrenal cortex
Maybe more interesting is the other side...acetylcholine.
Vitamin D and acetylcholine
Acetylcholine is so important and most people haven't heard of it.
It has two very different functions:
- Drives focus, resolve, and cognition...yes, literally thinking
- Powers the calming and restorative rest and digest part of the autonomic nervous system
Goodness...totally different effects.
Check out CBD and acetylcholine review since it's so important.
It may be most affected by Vitamin D.
In fact, Vitamin D is needed for acetylcholine receptors to actually function in a critical pathway for sleep.
There's a fascinating connection between Vitamin D, sleep, acetylcholine and the gut bacteria which is just being teased out.
The vagus nerve serves as a hub between the brain and the gut's nervous system.
Its primary player?
Watch what happens with Vitamin D supplementation:
demonstrated that exposure to short-term artificial sunlight heliotherapy not only increased serum 25-hydroxy vitamin D levels and control of mineral metabolism, but significantly increased measurements of cardioprotective vagal activity which were severely depressed at baseline
So...more light and vitamin d = more vagus nerve activity and better heart health.
Then, there's the physical connections of this rest and digest system (called the parasympathetic nervous system):
VITAMIN D INSUFFICIENCY IS ASSOCIATED WITH REDUCED PARASYMPATHETIC NERVE FIBER FUNCTION IN TYPE 2 DIABETES
Keep in mind that this system is key to calming and recovering from our fight or flight system.
There are implications there for panic attacks, anxiety, anger, impulse control, etc.
We have a review on how to support the vagus nerve.
All of this is tied heart function (heart races in fight or flight) so cardiovascular and metabolic impacts are strong when we're constantly in a state of elevation.
This alone may underlie Vitamin D's protective effects on the heart.
Alright, we covered some big players in the brain. Let's see how this actually manifests in mental health.
Vitamin D and mental health
You would expect that D's effect on the above players would show in actual mental health.
Let's go there now:
- Vitamin D and depression
- Vitamin D and the anxiety umbrella (panic attacks, OCD, etc)
- Vitamin D and schizophrenia
- Vitamin D and autism
- Vitamin D and dementia
- Vitamin D and ADHD
- Vitamin D and bipolar
- Vitamin D and mood disorders
Let's get started with the one that has received the most attention.
Vitamin D and depression
This is obvious since serotonin function figures so strongly in mood and depression.
It turns out that the real trick of serotonin is its effect on BDNF, our brain's fertilizer.
We'll cover this more in the neurogenesis section below but CBD and BDNF goes into why it's so important.
So...what does the research show?
First, there's seasonal affective disorder (SAD) where people see a rise in depression in the winter during the lowest amount of sunlight. This effect also applies to areas that get very little UV light due to latitude.
In fact, in the pandemic of 1918, latitude had a direct correlation with the severity of illness and even death.
There's a known connection between Vitamin D levels and the existence and severity of depression:
All the studies found that depressed subjects had lower levels of vitamin D compared to controls, and those with the lowest vitamin D levels had the greatest risk of depression
The severity piece is important.
As D levels drop, depression severity got worse which shows a direct correlation.
A large analysis of many studies found the following for D supplementation and depression:
A meta-analysis of all studies without flaws demonstrated a statistically significant improvement in depression with Vitamin D supplements
Maybe more interestingly…
The effect size was comparable to that of anti-depressant medication.
Anti-depressants are known to work for about 30% of the people who try them. Presumably, people who really have lower serotonin function. Till Tolerance builds.
It's interesting as the level of Vitamin D intervention and the group of people studied really matters.
For example, we know that estrogen is a powerful driver of serotonin and some of the studies looked at perimenopause and menopausal women. Testosterone is turned into estrogen in the male brain by aromatase. See Estrogen and mental health.
If estrogen is disappearing, good luck with any intervention! Check out our review for CBD and perimenopausal depression to understand why.
Vitamin D is known to have a neuroprotective effect as well which figures into depression that's driven by the immune response, glutamate, trauma, chronic stress, etc.
As researchers found:
The neuroprotective effect of vitamin D is associated with its influence on neurotrophin production and release, neuromediator synthesis, intracellular calcium homeostasis, and prevention of oxidative damage to nervous tissue.
The most important word there is "neurotrophin" which we'll discuss later in our neurogenesis section.
Essentially, repairing and rebuilding brain tissue and connections.
Let's turn our focus to anxiety.
Vitamin D and the anxiety umbrella (panic attacks, OCD, etc.)
At a surface level, anxiety is driven by an imbalance in glutamate (gas pedal) and GABA (brake pedal) in the brain.
We know this because benzos, the primary medication for anxiety, directly pump up GABA levels. With brutal addiction and tolerance.
As do most of the sleep aids.
Structurally, there are brain mechanisms as well with a mix match between the amygdala (emotional, fear center) and the prefrontal cortex (rational gatekeeper for amygdala signals).
The same insults (trauma, overactive immune response, glutamate, chronic stress, etc.) can impair this pathway.
Check out CBD and the mechanisms of anxiety to learn more.
A more recent study compared Vitamin D supplementation (50,000IU per week) for generalized anxiety disorder and found the following:
Anxiety score changes were significantly lower in vitamin D group than the controls (P = 0.001). Within group comparison indicated that depression in supplement group with lower vitamin D levels was significantly reduced.
Interestingly, they also looked at key inflammatory markers which all improved. This group were obese women with diabetes...a segment with significant inflammatory issues.
We'll see below as to Vitamin D's effect on obesity and weight.
Some studies in healthy groups do not find an effect which possibly means that deficiency is the key to benefits.
Another study looked at children on dialysis and found the following:
Serum levels of 25(OH)D were significantly lower in patients with anxiety than in normal controls
Again, another group of people with significant inflammation makeups.
This all points to Vitamin D's control over immune response and inflammation which we'll cover later.
Remember estrogen and progesterone for anxiety?
Another study looked at Vitamin D's effect on anxiety after ovaries were removed from rats:
The results of the study indicated that vitamin D3 supplementation at doses of 1.0 or 5.0 mg/kg/day decreased manifestations of anxiety-like profile in the middle-aged or old OVX rats, respectively.
Interestingly, estrogen PLUS Vitamin D had a significant impact.
Check out CBD and perimenopause anxiety to understand why.
Serotonin has a role to play in anxiety since it's a primary stress response buffer and we know Vitamin D promotes that pathway.
Check out CBD and serotonin for anxiety here.
Let's turn to developmental mental health issues.
Vitamin D and schizophrenia
First, the connection:
Vitamin D deficiency is highly prevalent in patients with schizophrenia, especially those in acute episodes. Low serum vitamin D concentrations may have an effect in the pathogenesis of schizophrenia, or schizophrenia and vitamin D deficiency may have a genetic cooccurrence.
In our review of CBD and schizophrenia, we do a deep dive into the drivers of the disease and inflammation, immune response, and other elements are all present.
It's clear that Vitamin D is needed at specific periods of brain development (third trimester, age 2-3, puberty, etc.) but what about supplementing after the fact?
An interesting study looked at Vitamin D and probiotics (see our Schizophrenia review for gut effects) and found the following:
Vitamin D and probiotic co-supplementation was associated with a significant improvement in the general (− 3.1 ± 4.7 vs. + 0.3 ± 3.9, P = 0.004) and total PANSS scores (− 7.4 ± 8.7 vs. -1.9 ± 7.5, P = 0.01).
Inflammation starts in the gut! Check out CBD and the gut barrier.
There is an increasing focus on the immune system being primed for hyperactivation and schizophrenia.
We'll cover in the immune section how Vitamin D can turn immune response up or down depending on need.
This alone may point to its benefits for developmental disorders.
The immune system has a second role to play besides just fighting infections...it's literally the architect of the brain!
Within the developmental vein, let's look at autism.
Vitamin D and autism
We did another deep dive into the risks and mechanics of autism at our CBD and autism review.
The clues have been building:
Lower concentrations of vitamin D3 may lead to increased brain size, altered brain shape, and enlarged ventricles, which have been observed in patients with ASD.
There are shared attributes with schizophrenia and Vitamin D definitely figures in.
Children born with low blood levels of vitamin D have 33 percent increased odds of autism compared with those born with high levels.
That study was mainly looking at early life (maternal and or neonatal).
What about afterwards?
Two open label trials found high dose vitamin D improves the core symptoms of autism in about 75% of autistic children. A few of the improvements were remarkable. The vitamin D doses used in these children were 300 IU/KG/day up to a maximum of 5000 IU/day (highest final 25(OH)D level reached was 45 ng/ml).
Autism is clearly in the wheelhouse of vitamin D with the following factors:
- GABA/Glutamate balance (hyperactivity, seizures, etc)
- Immune response - inflammatory markers
- Acetylcholine support - key to cognitive function
- Brain plasticity - neurogenesis and remodeling of existing pathways
Let's turn dementia.
Vitamin D and dementia
The new research on dementia is all about the immune system (see CBD and dementia).
Amyloid beta, the little protein that makes up the signature plaques??
Little bacteria killers...part of our immune response in the brain.
Vitamin D and Its Analogues Decrease Amyloid-β (Aβ) Formation and Increase Aβ-Degradation
Why isn't this front-page news? When half the population is deficient and our levels drop as we get older??
A study looked at Vitamin D levels and dementia/Alzheimer's risk:
Our results confirm that vitamin D deficiency is associated with a substantially increased risk of all-cause dementia and Alzheimer disease
- Under 25 nmol/L, risk was over 2 times!
- Between 25-50 nmol/L, risk was 50% more.
That gives us a good indication on where the real levels are for sufficient Vitamin D which has been incredibly difficult. We'll cover that at the end.
Vitamin D's real trick here (besides eating up plaques) is its neuroprotective function:
1,25(OH)2D3 treatment protects against glucocorticoid-induced apoptosis in hippocampal cells, likely to represent a mechanism of vitamin D-mediated neuroprotection.
Let's translate that little gem.
Essentially, Vitamin D supplementation (treatment) prevents the loss of critical brain cells that result from our stress response system.
Check out CBD and neuroinflammation to get to the heart of this.
This was just one of many aspects with D that you read about in the review above.
Then, there's the rebuilding process (neurogenesis). This is as important for dementia as preventing the destruction to begin with.
Vitamin D upregulates the production of several neurotrophin factors, such as glial cell line derived neurotrophic factor (GDNF) and neurotrophin-3 (NT-3), which promote the survival, development and function of neurons.
What you just read maybe the most important sentence is this whole review...at least in terms of mental health.
This is THE new direction for mental health across every known mental health issue.
And it relies on D. If D drops as we get older, it begs the question of whether mental deterioration is just a function of reduced replenishment (plus the hormones that drive it).
The other big player in dementia research is acetylcholine. Check our review here.
As we know, Vitamin D directly supports acetylcholine levels from above.
Acetylcholine is a great segue into our next section.
Vitamin D and ADHD
First, is there a connection between D levels and ADHD?
The mean serum vitamin D level of children with ADHD (19.11±10.10 ng/ml) was significantly lower than that of the control group (28.67±13.76 ng/ml) (P<0.001).
New research is really pointing to acetylcholine as the driver of this issue along with developmental risks.
What about D supplementation?
The mean scores of the CPQ, SDQP and SDQT showed a significant difference in the two groups after intervention (p < 0.05).
The main impact was on impulsivity which is solidly under the control of serotonin (see CBD and serotonin).
A study looked at Vitamin D deficiency and ADHD:
The diagnosis of vitamin D deficiency was significantly greater in children with ADHD compared with the control group ( P < 0.05). Children with ADHD had significantly ( P = 0.0009) lower values of serum vitamin D (17.23 ± 8.98) than the control group(31.47 ± 14.42).
Maybe more importantly:
The group receiving vitamin D supplementation demonstrated improvement in cognitive function in the conceptual level, inattention, opposition, hyperactivity, and impulsivity domains.
This is really a confluence between serotonin, acetylcholine, and glutamate. Powerful players all under the management (partially) of Vitamin D.
Let's turn to bipolar.
Vitamin D and bipolar
Bipolar follows similar risk profiles as schizophrenia and to a lesser extent, autism.
There are definite correlations between D levels and bipolar:
Vitamin D deficiency was recorded in more than 22% of patients with bipolar disorder (95% CI, 16.2-31.3) and in almost 35% of patients with schizophrenia or schizoaffective disorder (95% CI, 28.4-41.5).
This isn't unexpected given the developmental nature of the illness and Vitamin D's role in development.
GABA and glutamate balance is a critical component in bipolar which points to the swings (and rebound) in mood.
A study looked at Vitamin D supplementation for bipolar:
Following an 8 week Vitamin D3 supplementation, in BSD patients, there was a significant decrease in YMRS scores (t=−3.66, p=0.002, df=15) and Children's Depression Rating Scale (CDRS) scores (t=−2.93, p=0.01, df=15); and a significant increase in ACC GABA (t=3.18, p=0.007, df=14).
GABA in a specific brain region (ACC) is critical to calm the mania storm and Vitamin D increased it there!
Check out CBD and bipolar to learn more about the mechanics.
This is by no means the full list of mental health issues but the fact that Vitamin D deficiency is tied to such a wide swath of the field is fascinating.
It's not surprising given the effects it has on key aspects of brain function:
You just listed the usual suspects in every mental health issue.
Let's turn our attention to inflammation, one of those culprits.
Vitamin D and inflammation and immune response (autoimmune!!)
Inflammation is the new boogie boo in the health world.
That's not entirely fair.
Inflammation is an important process for repair and response to a host of bad things in our body.
The repair function is embedded right in the inflammatory response!
It's chronic or hyper inflammation that matters!
Inflammation lies clearly under the immune system's domain.
Here's the key part...Vitamin D functions as a "modulator" of the inflammatory response.
It doesn't just push it up or down. It adjusts according to need.
So important where too little will make you susceptible to illness while too much will lead to autoimmune where the system attacks our own cells!
Let's drill down further into this role it plays.
First up cytokines, the little assassins of our immune system and mediators of the inflammatory response (both up and down).
In cases of infection, Vitamin D can ramp up immune response...this is well known.
In colder (less sunlight) latitudes, there is a defined flu season.
In the tropics, not only is there less flu but it's sporadic across the months of the year.
We're more focused on what it does when the immune response is too strong!
This is the litany of modern diseases that you see all the TV ads for (medications).
It's a booming business with price tags in the 10's of thousands of dollars.
We could spend an entire review on just this question but we'll hit the highlights.
First, is there an association between D levels and autoimmune?
it was discovered that supplementation with 1,25(OH)2D3 could prevent both the initiation and progression of experimental autoimmune encephalomyelitis (EAE) and collagen-induced arthritis (CIA), experimental models of MS and RA, respectively
Other studies point to similar effects across the range of autoimmune diseases from Crohns to diabetes (yes, it's autoimmune in nature).
Then there's the latitude connection between autoimmune diseases and Vitamin D (via sunlight).
MS is correlated with the month of birth, with for the northern hemisphere a higher risk in April and a lower risk in October and November
Look at the impact of supplementing D when a child:
In addition, vitamin D supplementation in early childhood might reduce the risk of developing T1D up to 30% depending on the supplementation frequency
One thing we can see from the chart of ongoing tests is that the levels of supplementation have to be pretty high (always test levels). We'll speak to this issue at the end since it's a huge problem.
A driving theory of autoimmune now is that the issue starts in the gut. Leaky gut allows bacteria to freely cross into our bloodstream and the body's immune system responds accordingly.
If this is chronic, it sets up a situation of hyperactivation.
Like we said, with immune response there's always collateral damage.
Let's turn our attention to the gut...where autoimmune resides.
Vitamin D and the gut (microbiome)
Check out CBD and the gut barrier but Vitamin D has a side hustle which is very important.
D is in charge of growing and maintaining our epithelial lining.
This is the inner "skin" if our body from arteries to….gut barrier!
Vitamin D is responsible for the barrier function of the intestinal epithelium and for the modulation of the bowel immune system, hence, low levels may be associated with greater gut permeability and, consequently, with GM-induced metabolic endotoxemia that induces a low-grade inflammation
What you just read is the heart of autoimmune. The ongoing trigger!
And Vitamin D is at the center of this.
Keep in mind that this means Vitamin D supplementation is a long term process. Repair and damage take time to address so 1 week or even 4 weeks is not the course of action.
When researchers knock out vitamin D function via the gene, the gut microbiome quickly goes into disarray:
In animals with vitamin D depletion and the knockout of the VDR, the GM dysbiosis favors metabolic disorders
On the flip side, when they jack up VDR activity, protection for colitis was the result.
By the way, you can get a 23andme gene study. In the raw data, you can type in VDR and see if you have genes that are impacted.
My VDR genes are terrible which is why it's so hard to move the dial even at 10K a day.
Just a note.
Remember how overactive immune response was key to mental health issues?
Is there something that's causing this...bacteria that are crossing the blood-brain barrier and wreaking havoc (not to mention dementia)?
As we mentioned above, Vitamin D is key to all our "inner skin," and the blood-brain barrier is no exception:
Calcitriol Prevents Neuroinflammation and Reduces Blood-Brain Barrier Disruption and Local Macrophage/Microglia Activation
To understand why this is so important, check out CBD and neuroinflammation.
Let's turn to our favorite section.
Vitamin D and neurogenesis (brain repair)
This process is key to addiction and mental health (two sides of the same coin, really).
Remember how one of the key components of relapse was levels of BDNF (along with stress).
BDNF is going to the superstar of the next decade.
It's our brain's fertilizer.
All the exciting research on psilocybin points to an explosion of BDNF (see psilocybin).
In every review we have on mental health, BDNF is front and center.
It also applies to neuropathy, pain, and much more.
So...what's the connection with Vitamin D?
First, Vitamin D supports serotonin function. Serotonin directly drives BDNF..
In fact, in studies where BDNF is blocked, SSRIs lose their anti-depressant (and neurogenesis) effect.
See how do SSRIs really work.
BDNF is called a neurotrophin (grower of neurons).
As for Vitamin D:
First, a prenatal vitamin D deficiency disrupts brain development and alters the expression of growth factors and neurotrophin receptors in the adult dentate gyrus
NGF (nerve growth factor) is another powerful player in growing brain connections.
The NGF release in vitamin D-treated group was significantly higher than in untreated control group. The protective effect of vitamin D against cytotoxicity was also observed.
Vitamin is a steroid after all. It promotes growth and activity by nature.
In the brain, that's driven by the neurotrophins and Vitamin D is all over this pathway:
Vitamin D regulates expression of neuron growth factor (NGF), neurotrphin-3 (NT-3), neurotrophin-4 (NT-4) and glial cell derived neurotrophic factors (GDNF).
Goodness. And half of us are deficient while 80% of African Americans are essentially dealing with a metabolic handicap.
Let's turn to an interesting sidekick for Vitamin D.
Vitamin D and magnesium
Magnesium is so impressive for brain health, neurogenesis, and sleep that we did a full review of it here.
There's a curious connection between mag and Vitamin D however.
Here's one example:
High intake of total, dietary or supplemental magnesium was independently associated with significantly reduced risks of vitamin D deficiency and insufficiency respectively.
Mag appears to be key to VItamin D function.
Mag is involved in the entire process of making D in our bodies:
Previous studies have shown that the activities of three major enzymes determining 25(OH)D level [22–25] and vitamin D binding protein  are magnesium dependent
More importantly, magnesium supplementation would move the dial for people who have trouble absorbing Vitamin D.
This is very interesting and magnesium is wholly impressive on its own right (see the review).
The two may be powerful allies in just about every pathway in the body and brain.
Let's turn our focus to sleep.
Vitamin D and sleep
Everything we've discussed above depends on one thing. Good, deep sleep.
Repair, clearing out waste in the brain, mental health.
Sleep is front and center.
First, the summary level of many different studies:
By comparing the lowest verse highest levels of serum vitamin D, we found that participants with vitamin D deficiency (VDD) had a significantly increased risk of sleep disorders
Interestingly, the shortlist of issues that come from sleep disruption matches up pretty well with Vitamin D deficiency:
Previous studies revealed that excessive sleep or sleep deprivation were associated with increased risk of adverse health events, including type II diabetes, hypertension, cancers, and all-cause mortality
"All-cause mortality" indeed.
You mean this??:
Intake of ordinary doses of vitamin D supplements seems to be associated with decreases in total mortality rates.
There's a host of studies on D levels, supplementation, and sleep quality.
We highly recommend you check out this video from Dr. Gominak:
Her work is outstanding! You'll have a completely different take on D and sleep (plus the gut).
Vitamin D affects so many different pathways that its hard to pinpoint just one but we'll try.
Deep in our hypothalamus (part of the "reptilian" brain) that governs basic housekeeping, there are defined neurons that literally paralyze body areas so that we can enter deep sleep.
There are Vitamin receptors right on the neurons.
In fact, Vitamin D is the key that turns on acetylcholine production so that this system can work.
Acetylcholine runs our rest and digest part of the autonomic nervous system which ties in directly with sleep of course!
Most importantly, what's the effect of Vitamin D supplementation and sleep quality.
An intervention study reported that vitamin D supplementation (D3) in veterans (50,000 IU/week) increased their sleep duration . Another double-blind clinical trial showed use of vitamin D supplementation (50,000 IU/fortnight for 8 weeks) facilitated sleep duration and quality in people with sleep disorder .
Look at those numbers...50,000 IU per week!
The government recommendation is 400 IU...we'll get to that in the last section.
Keep in mind that all of your repair happens when you sleep (well) and this includes removing the daily waste of brain activity...especially its immune system response (amyloid beta plaques, etc).
In our review of mental health issues, everyone had a component with impaired sleep.
Some of the research on magnesium and glycine are equally impressive for sleep.
Let's turn our attention to weight and metabolic processes.
Vitamin D and weight
Vitamin D is all over the entire metabolic complex, including sugar, insulin, and weight.
Its interaction with the gut may be paramount there.
We'll start with weight:
After using vit D supplementation for 6 weeks, WT, WC, and body mass index (BMI) were decreased significantly and serum vit D increased significantly compared to control group
WT is weight. WC is waste circumference.
The dosage? 50,000 IU weekly.
The interaction between D and fat is actually fascinating.
Obese people have trouble with D deficiency as our fat cells store D.
Think about what fat really is in terms of our ancestors.
It's protection against famine or starvation later on. Essentially, a store of energy in case we're not eating much for weeks.
Our basic machinery is about the same as 40,000 years ago unfortunately.
So...D is so important that the body will store excess away in fat.
In fact, look at what happens when people lose weight:
A greater degree of weight loss, achieved through either a reduced-calorie diet or increased exercise, is associated with increased circulating 25(OH)D concentrations.
It's a storage mechanism! D is that important.
Fat is just a net effect of an entire system though. What about insulin and sugar?
Insulin function is the final nail of diabetes but Vitamin D is early in the process:
More recently, it was also shown that vitamin D prevents epigenetic alterations associated with insulin resistance and diabetes.
Remember, as a steroid, Vitamin D can turn genes on and off throughout the body.
As for diabetes, the islets cells that eventually lose function do so as a result of excess calcium and oxidative stress.
Remember that Vitamin D's primary role in the body is that of the manager of calcium (hence the bone connection).
Vitamin D deficiency contributes to both the initial insulin resistance and the subsequent onset of diabetes caused by β-cell death.
The net result is an increase in blood sugar from this dysfunction.
Vitamin D's effect there:
Intake of vitamin D supplements led to a marginally significant decrease in fasting blood glucose
This whole system could take an entire review.
So here's the interesting question. Why would a person lose weight SOLELY from increasing Vitamin D?
Is D so important to the body, that having too little of it will cause weight gain simply to keep a reserve?
Or is D directly involved in the process of fat creation?
Perhaps both and THAT is a separate, full review.
Check out CBD and weight to learn more.
Let's turn to brain function.
Vitamin D and brain function
We've already talked about D and mental illness...brain dysfunction.
Let's turn quickly to just maximizing standard function.
Thinking. Memory. Cognition!
A large study looked at many other studies and found the following:
The meta-analysis provided evidence that low vitamin D is cross-sectionally associated in adults with impaired episodic memory and executive dysfunction, especially mental shifting, informational updating and processing speed.
The "cross-sectionally" part is important as it balanced for other factors such as gender, rate, location, income, health, physicality, etc.
This reduces the difference down to one thing...Vitamin D levels.
Memory is important but executive function is what makes humans human.
Cognition. Thinking is a better word!
The effects on neurotransmitters tied to cognition are obvious and we looked at those above (serotonin, acetylcholine, norepinephrine, glutamate, etc.).
Then there's the heavy lifters of building new connections...BDNF, NT3, etc.
All driven by Vitamin D.
Maybe more interestingly, as we get older is the health of our plumbing in the brain.
Vitamin D was tied to fewer strokes and increased cardiovascular health...key players in brain health.
There's also the development of the brain which relies on D.
We see the impact on intelligence and brain function across many studies now:
The scientists found that the lower the subjects’ vitamin D levels, the more negatively impacted was their performance on a battery of mental tests.
And this one:
The data show that those people with lower vitamin D levels exhibited slower information-processing speed.
Another study found a 4 times increase in cognitive impairment with D deficiency.
Iodine and Omega 3 also pop up on this front.
Let's look at the skin.
Vitamin D and skin
We already talked about our internal skin...the epithelial lining of our arteries, brain, and gut.
What about the outer skin?
We've already discussed how skin color may simply be a lever to control Vitamin D production.
UV light is needed to produce most of our Vitamin D so it's not surprising that Nature would build a protection from cancer effects of UV:
It is well accepted in the scientific community that vitamin D compounds protect the skin against the hazardous effects of many skin aging-inducing agents, including ultraviolet (UV) radiation
One study predosed skin cells with Vitamin D and it prevented damage for a strong dose of UV radiation.
Look at animal studies where VDR gene activity is reduced:
VDR−/− mice are characterized by skin thickening and wrinkling, alopecia, have growth retardation, osteoporosis, kyphosis, ectopic calcification, progressive loss of hearing and balance as well as a relatively short lifespan
Hair loss? Interesting.
Those two reviews go through massive numbers of different pathways affected for healthy skin maintenance.
Some of which deal with cancer.
Vitamin D and cancer
There's quite a bit of research on this front.
accumulating data suggest that the metabolism and functions of vitamin D are dysregulated in many types of cancer, conferring resistance to the antitumorigenic effects of vitamin D and thereby contributing to the development and progression of cancer.
This review and others then dive into Vitamin D and specific cancer risks.
It can be very technical and overwhelming.
We have a natural anti-cancer system in the body and it resides firmly in the immune system.
In fact, our immune system will detect and kill precancerous or virally infected cells when working properly.
This is the whole-cell birth/death system that operates around the clock.
There are also the clues from sunlight exposure that we see everywhere else:
In more cloudy northern latitudes of US, a prostate, breast and colon cancer belt has been documented to occur 2-3 times more commonly than the sunnier regions.
Its not just prevention though:
Besides cancer prevention and cell death, vitamin D can also cause tumor growth retardation as well as tumor regression because of its angiogenesis inhibitory action, which deprives the cancer cells of their nutrients and oxygen for growth and survival.
There's a fascinating clue in that review in terms of dosage:
It is now recognized that maintaining a serum calcifediol concentration of 80 nmol/ l (32 ng/ ml) or more is useful in the prevention of osteoporosis, CVS diseases, certain autoimmune diseases and some forms of cancers.
80 nmol/l. Interesting. Let's go there now.
Vitamin D supplementation (mixed messages)
This is really heartbreaking.
Look at everything we've discussed (didn't even have time for cardiovascular health).
Many government agencies have been recommending supplementation levels of 400 IU (international units) and even downplaying the importance of D.
They made the big jump (sarcasm) of raising D deficiency from below 25 to below 30 nmol/l.
But we just saw 80 nmol/l as key to cancer prevention.
Cancer is an intersection of genes, inflammation, immune response, etc which impact just about every system in the body and brain.
There has been so much back and forth on Vitamin D supplementation.
Here's the issue...the government's primary goal was preventing bone wasting and rickets.
400 IU might do that but we're not all coming over on month-long journeys in ships any longer.
We now know so much about what D does (the past 7000 words).
So...what about supplementation?
First, get tested! You have to know your Vitamin D levels and keep knowing them.
Every 6 months is a good plan.
Too little or too much D have similar profiles.
The RDA for D is still listed at about 600 IU but look what endocrinologist say:
The Endocrine Society states, for example, that to maintain serum 25(OH)D levels above 75 nmol/L (30 ng/mL), adults might need at least 37.5 to 50 mcg (1,500–2,000 IU)/day of supplemental vitamin D, and children and adolescents might need at least 25 mcg (1,000 IU)/day .
75 nmol/l….just below the 80 nmol/l number for cancer.
The studies above across a range of issues, looked at 50,000 IU per week (essentially 10K per day for 5 days).
You can get your raw genetic data from 23andme. Type in VDR and see how you process Vitamin D. Stratagene from Dr. Ben Lynch will actually analyze this and other key genes.
I have three variants of key VDR genes that are very poor!
I took 5000 IU for half a year and barely budged my serum level VItamin D.
You have to look at your levels and adjust accordingly.
I'm up to 10,000 IU daily now and it's slowly moving.
That brings up a good question...daily or once per week or month?
Studies looked at both and found they ended up at the same place in terms of D levels, although the big dose ramped up faster.
What about the time of day?
Sleep factors in here. Some people find that Vitamin D supplements before bed can interfere with sleep. Remember, it's a steroid and there's research on how it can disrupt melatonin function if taken before bed.
Taking D in the morning can actually improve sleep at night.
So...the net take away for supplementation:
Get tested regularly...it's cheap and if your doctor hasn't been doing this anyway, maybe find another doctor.
With the ACA law, it should be covered at 100% under preventative.
1000-2000 IU daily is probably a low level with 5-10,000 IU at the top end for supplementation.
Again, based on serum levels.
70-80 nmol/l is starting to look like the optimal level.
We need better research for true optimal levels.
The Massai tribe is an interesting study.
They're herders who spend all day long in the sun.
Essentially, this is how all our ancestors lived 20,000 years ago and in the same sun maybe 100,000 years ago.
Their D levels?
The mean serum 25(OH)D concentrations of Maasai and Hadzabe were 119 (range 58-167) and 109 (range 71-171) nmol/l, respectively.
They have very dark skin so Vitamin D creation is significantly ramped down.
And yet...they're at 120 nmol/l.
Now...other factors come into play but that appears to be the highest level based on how evolution designed us (same blueprint operating today).
We look forward to real research on optimal levels but our guestimate is between 80-100 nmol/l.
Obesity, cancer status, etc. can affect this.
For example, Vitamin D was protective against the pro-growth effects of estrogen in breast tissue (key for cancer).
Magnesium is a key cofactor for Vitamin D function. The "ates" like glycinate, threonate, and citrate are impressive (see here).
Vitamin D appears to best if taken in the morning even for effects on sleep.
Now, do you see why this is all so frustrating in terms of recommendations from our government?
The possible effects for people with darker skin is downright heartbreaking. 80% deficient based on their already watered-down levels (below 25 nmol/l) when our ancestors were at 100+.
600 IU indeed.
Always work with a doctor or naturopath with any supplement!
The information provided here is not intended to treat an illness or substitute for professional medical advice, diagnosis, or treatment from a qualified healthcare provide