Vitamin D

Vitamin D is incredibly important.  Remember Vitamin D is more than a vitamin- it's an essential pro-hormone.  Vitamin D influences more than 200 human genes, which could be impaired when we do not have enough vitamin D. 

Many people are deficient and Vitamin D for a number of reasons, including diet and lifestyle.   The Vitamin D Council believes that trying to get enough vitamin D from your diet is unlikely to give you the vitamin D you need.  You can check your vitamin D level at your doctor's office, or by way of a home Vitamin D test.   

The health conditions, to date, linked with Vitamin D can be summarized as:

Cardiovascular health

• Heart disease
• Hypertension

Bone and muscle health

• Rickets
• Osteoporosis
• Fractures
• Osteoarthritis
• Muscle weakness

Insulin and glucose metabolism

• PCOS
• gestational diabetes
• Type 1 diabtes
• Type 2 diabetes

Gatrointestinal health

• Colonic polyps
• Colon cancer
• Liver fibrosis
• Crohn's disease

Immunity 

• Rheumatoid arthritis
• Multiple sclerosis
• Systemic Lupus
• Crohn's disease

Cancer- at least 17 different cancers including

• Bladder
• Breast
• Esophageal, gatric, rectal, colon
• Uterine
• Ovarian
• Non hodgkins lymphoma

Skin health 

• Atopic dermatitis
• Eczema

Childhood conditions

• childhood asthma
• reduce the risk of autism, both in animal and human studies

Mental illness, and brain function

• Mood
• Alzheimer's
• schizophrenia
• autism

Fertility and gynecologic conditions

• PCOS
• Fibroids
• Endometriosis

Pregnancy and placental related

• prematurity (preterm birth)
• preeclampsia and fetal growth restriction
• gestational diabetes
• possibly reduce the risk of miscarriage
• contributes to the regulation of placental inflammation.  

 Vitamin D is a steroid super-pro hormone traditionally known to be important in intestinal absorption of calcium and the regulation of calcium homeostasis, and bone differentiation.  Yet, most of us are Vitamin D deficient.  For more than 40 yrs, there has been the unchallenged message that humans should avoid direct sun exposure and always wear sun protection when outdoors. But sunscreens block 98% of vitamin D and most of us work indoors.   The recommendation was been that you can get more than enough vitamin D from dietary sources.  But in fact very few foods naturally contain vitamin D, and most vitamin D–fortified foods or mild contain only 100 IU of vitamin D in a serving, which is totally inadequate for satisfying the body's vitamin D requirement (the U.S. fortifies milk, the UK does not). Even in Australia, where you would think they should have 'no worries' about Vitamin D, the sun-safe message has been strongly promoted and they now recognize that vitamin D deficiency has become a major health issue for both children and adults.  In recent years, the incredible vital importance of vitamin D has been revealed in many organs and in a wide range of disease processes.  

There are two major types of vitamin D:

1.  Vitamin D2 (ergocalciferol) – which is synthesized by plants and is not produced by the human body.

• Mushrooms  can be a good source.  However, commercially grown mushrooms are often grown in the dark and contain very little D2.  Certain brands are treated with UV light. These mushrooms can provide anywhere from 130–450 IU of vitamin D2 per 3.5 ounces (100 grams

2. Vitamin D3 (cholecalciferol) – which is made in large quantities in the skin when sunlight strikes bare skin. It can also be ingested from a small number of foods.  Food sources include:

• oily fish – such as salmon, sardines, herring and mackerel
• egg yolks
• fortified foods – such as most fat spreads and some breakfast cereals.  Also milk in the U.S. and some countries. 

The metabolism of Vitamin D is complex, and dependent on absorption, transfer and activation proteins.   Vitamin D that enters the systemic circulation though the skin or ingestion undergoes 2 stages of hydroxylation. The first stage takes place in the liver forming 25(OH)D3, the second stage takes place in the kidneys forming 1,25 (OH) 2D. Intracellular targets of vitamin D also requires a vitamin D receptor (VDR), a member of the nuclear steroid hormone receptor superfamily.   In the absence of vitamin D, the VDR remains mostly contained in the cytoplasm. 

Vitamin D deficiency world wide has been described in epidemic proportions.  It is estimated that about 60% of people in the UK are vitamin D deficient, with children under five, people with dark skin and the elderly being particularly vulnerable.   
During the autumn and winter, you need to get vitamin D from your diet because the sun isn't strong enough for the body to make vitamin D.   People with higher risk include those:  

• who have very little or no sunshine exposure.
• who usually wear clothes that cover up most of your skin when outdoors
•  with dark skin from African, African-Caribbean and south Asian backgrounds may also not get enough vitamin D from sunlight 
• with genetic variations which inhibits metabolism of Vitamin D

The most natural way to get vitamin D is by exposing your bare skin to sunlight (ultraviolet B rays).  Large amounts of vitamin D3 (cholecalciferol) are made in your skin when you expose all of your body to summer sun.  You don’t need to tan or burn your skin to get vitamin D. You only need to expose your skin for around half the time it takes for your skin to begin to burn. How much vitamin D is produced from sunlight depends on the time of day, where you live in the world and the color of your skin. The more skin you expose the more vitamin D is produced. However, there are many factors which can affect the amount of vitamin D your body makes from exposure to the sun. These are:Dark skin requires 5-10 x sun exposure

• Your type of skin.  If you are dark skinned, you might require 5-10x more sun exposure than fair skinned for the same Vitamin D.  
• The amount of skin you expose. The more skin you expose, the more vitamin D you can produce.
• How old you are. As you get older, your skin has a harder time producing vitamin D.
• Whether you’re wearing sunscreen. Sunscreen can block 98%  of vitamin D production.
• The altitude you’re at. The sun is more intense on top of a mountain than at the beach. This means you make more vitamin D the higher up you are (at higher altitudes).
• Whether it is cloudy. Less UVB reaches your skin on a cloudy day and your skin makes less vitamin D.
• Air pollution. Polluted air soaks up UVB or reflects it back into space. This means that if you live somewhere where there is lots of pollution, your skin makes less vitamin D.
• Being behind glass. Glass blocks all UVB, so you can’t make vitamin D. 

Vitamin D and the Sun, and Mitochondria

Interestingly, sunshine both makes vitamin D and activates mitochondria.  Not surprisingly, a link has been found between vitamin D and mitochondria activation.  Alongside poor bone health, muscle fatigue is a common symptom in vitamin D deficient patients. This fatigue could be due to reduced efficiency of the mitochondria: the 'power stations' within each cell of the body.Mitochondria use glucose and oxygen to make energy in a form that can be used to run the cell - an energy-rich molecule called ATP. Muscle cells need large amounts of ATP for movement and they use phosphocreatine as a ready and available energy source to make ATP. The mitochondria also replenish this phosphocreatine store after muscle contraction and measuring the time taken to replenish these stores is a measure of mitochondrial efficiency: better mitochondrial function is associated with shorter phosphocreatine recovery times.
 

Considerable data suggests a role for vitamin D in cancer therapy and prevention.  The first human evidence to suggest a relationship between vitamin D and cancer prevention came from ecologic or geographic studies which suggested increased sunlight (UVB) exposure or populations living in lower latitudes had a lower incidence of colon cancer, and later a reduced risk of prostate cancer.   It is now known that vitamin D co-regulates cell proliferation, differentiation and apoptosis in numerous tissues, including cancers.  Vitamin D compounds have now been found to have a strong anti-tumor effect, and help potentiate the antitumor actions of many more traditional anticancer agents.  This has been found to be helpful for at least 17 types of cancer including prostate,lung,ovary, breast, ladder,pancreas and some brain cancers.  This is attributed to the important role of vitamin D in immunity, regulating inflammation and  antiangiogenic effects.   Tumor behaviour and patient outcome likely depend on both vitamin D and VDR status.  VDR may actually potentiate tumor growth when not bound to Vitamin D.   It is possible that local production of 1,25(OH)2D, dependent on adequate serum 25(OH)D levels and tissue CYP27B1 activity, may be more important than levels of serum 1,25(OH)2D which do not correlate closely with vitamin D status.  

"Activated vitamin D is one of the most potent inhibitors of cancer cell growth," says Michael F. Holick, PhD, MD, who heads the Vitamin D, Skin, and Bone Research Laboratory at Boston University School of Medicine. "It also stimulates your pancreas to make insulin. It regulates your immune system."  

Also, see blog post and cancer page

Vitamin D’s impact on glucose has only recently been identified; some data is not clear as this is a new area of research.  However, we know Vitamin D  is involved in insulin secretion, tissue sensitivity to insulin and so plays a significant role  in hormonal regulation of glucose metabolism.  There is a significant and inverse relationship between blood levels of vitamin D and the risk of type 2 diabetes among a wide range of vitamin D levels.  The association between vitamin D insufficiency and obesity has been extensively investigated in adults. The largest meta-analysis performed by Chinese investigators in 2015  demonstrated a pronounced difference in vitamin D insufficiency (3.7 x more likely) among obese patients.  Vitamin D helps regulate systemic inflammation and influences the synthesis of adipokines by fat tissue. Vitamin D deficiency could lead to obesity by impaired tissue insulin sensitivity, as well as subclinical inflammation in adipose tissue.  Obesity-associated insulin resistance is accompanied by elevated levels of pro-inflammatory cytokines, such as TNF-alpha, IL-6, and IL-1-beta.   Long-term monitoring of obese patients receiving vitamin D supplementation revealed an improvement of the adipose tissue inflammation that was a result of inhibited TNF-alphaactivity. Vitamin D supplementation in patients with diabetesmellitus type 2 helps decrease C-reactive protein and TNF-alpha concentrations,  and increase leptin concentrations.   At least one study has shown that fasting glucose levels, insulin levels and insulin resistance all improved with vitamin D supplementation.   Data suggests that each increase of 4 ng/mL of vitamin D in the blood is associated with a 4% lower risk of type 2 diabetes.Additionally, this study suggests that pro-inflammatory cytokines that are thought to contribute to insulin resistance were down-regulated with this vitamin D supplementation. Vitamin D supplementation appears to reduce inflammation as part of the body’s normal healing/tissue repair processes.Over 10,000 children born in Finland during 1966 were studied.   Those children who received 2000 IU/ml vitamin D the first year of life (by reporting) had a 5 x less risk of type I diabetes after a 31 year followup.  A more recent (2013) meta-analysis study also concluded that  vitamin D intake during early life may be associated with a reduced risk of type 1 diabetes, although maternal intake during pregnancy was not found to be protective.  

Vitamin D is integral to our immune system; some experts and studies are recommending to add or increase vitamin D supplementation during a variety of illnesses, including colds, flu, respiratory illness, asthma, and more.  Vitamin D deficiency has been strongly linked to an auto immune condition, multiple sclerosis.  It's long been known that people living in higher latitudes (more northern) have a high prevalence of multiple sclerosis, and an earlier onset compared to those living below 32 degrees latitude.  Vitamin D has been shown to decrease the risk of developing multiple sclerosis, and also improved symptoms in those patients with the condition. Vitamin D has also been linked to improvement in other immune conditions including rheumatoid arthritis, and systemic lupus.  

One potential role of Vitamin D is to help regulate dendritic cells which are known to be very important in immunity regulation. Consequently, vitamin D metabolites are frequently used in protocols to develop therapeutic dendritic cell therapies for autoimmune diseases 

Vitamin D is a vital component of neurotransmitters in the brain. Three major neurotransmitters in the brain requiring adequate amounts of vitamin D include serotonin, oxytocin, and vasopressin; serotonin is a neurotransmitter vital for transmitting nerve impulses. Serotonin is also important for mood regulation; pain perception; gastrointestinal function, including perception of hunger and satiety; and other physical functions. Oxytocin is released from the brain when it is needed for a variety of body needs, including labor & delivery at the end of pregnancy, during sexual arousal, and it is often referred to as “the love hormone” because of its impact on emotional relationships. Vasopressin is an anti-diuretic hormone that regulates fluid balance within the body and bloodstream. It works to prevent excess fluid loss and helps maintain homeostasis (normal internal chemistry) by maintaining the concentration of dissolved particles, such as salts and glucose, in the blood. Reviewing all 3 of these neurotransmitters and their major functions, we can see how a shortage of vitamin D would impact nearly all normal body functions and even our relationships, moods, and emotions.  Some studies have shown significant positive associations between higher vitamin D intake (4000 vs 400 ml/IU) levels and nonverbal (visual) memory, which also utilizes executive functioning processes, after just 18 weeks of intake. Other studies suggest a protective role of vitamin D in dementia like Alzheimer's disease (AD).  Vitamin D was also found to prevent amyloid-beta cytotoxicity, one of the major components of AD pathology, in primary cortical neurons. This opens a new strategy in treatment or at least in slowing down the progression of this disease. 

Autism rates have increased in the past few decades, reflecting population wide  vitamin D deficiency.  Children who are, or who are destined to become, autistic have lower 25(OH)D levels at 3 months of gestation, at birth and at age 8 compared to their unaffected siblings.   Vitamin D therapy has also been shown to improve symptoms in 75% of children with autism.  Vitamin D deficiency in pregnant and lactating mothers has now also been associated with higher rates of autism, which suggests we can reverse the trend and make a significant impact on autism.  Lack of sunlight in pregnancy has been linked to  autism and other learning disabilities among children years later.   According to one study in Molecular Psychiatry, women with low vitamin D levels at 20 weeks of pregnancy are more likely to have children with symptoms of autism.  Children born to women who had low blood levels of vitamin D while pregnant more than double their risk of autism according to another study of more than 4,000 children in the Netherlands.  The benefit of vitamin D may be related to the duration of supplementation with some studies showing benefit when vitamin D is started a year before pregnancy.    Importantly, it has been suggested we can help prevent autism by supplementing pregnant and lactating women (5000 IU/day) and infants and young children (150 IU/kg/day) and checking 25(OH)D levels every 3 months.   

Gut bacteria and the microbiome may also play an important role in autism.

Are Vitamins helpful for fertility?

Apart from the well known effects of vitamin D on maintaining calcium homeostasis and promoting bone mineralization, there is some evidence suggesting that vitamin D also modulates human reproductive processes.  Several observational studies reported a better in-vitro fertilization outcome in women with sufficient vitamin D levels (≥30 ng/ml), which was mainly attributed to vitamin D effects on the endometrium. One randomized controlled trial found an increased endometrial thickness in women with polycystic ovary syndrome (PCOS) receiving vitamin D during intrauterine insemination cycles. Further, vitamin D supplementation had a beneficial effect on serum lipids in PCOS women. Vitamin D treatment improved endometriosis in a rat model and increased vitamin D intake was related to a decreased risk of incident endometriosis. Vitamin D was also favorably associated with primary dysmenorrhea, uterine leiomyoma (fibroids) and ovarian reserve in late reproductive aged women.

A number of studies also suggest that vitamin D is a powerful factor against fibroids, resulting in inhibition of tumor cell division and a significant reduction in its size, however, the exact role of this compound and its receptor in the pathophysiology of fibroids is not fully understood. According to available studies, vitamin D and its analogs seem to be promising, effective, and low-cost compounds in the management of fibroids and their clinical symptoms, and the anti-tumor activities of vitamin D play an important role in fibroids biology. The synergy between vitamin D and selected anti-fibroid drugs is a very interesting issue which requires further research. 

In women undergoing in-vitro fertilization, a sufficient vitamin D level (≥40 ng/ml) should be obtained. Vitamin D supplementation might improve metabolic parameters in women with PCOS. A high vitamin D intake might be protective against endometriosis and fibroids. 

Vitamin D  is really an essential prohormone your body makes every day.  But due to modern lifestyle, we don't usually make enough.  It plays a critical role in many processes including bone formation, calcium metabolism, placental development controlled placental invasion and brain development.  In addition to the effects in adults (see figure right), compelling  new evidence strongly indicates that vtamin has D been shown to reduce the risk of a variety of pregnancy related complications, many of which can be traced to placental function.  

• prematurity (preterm birth)
• preeclampsia and fetal growth restriction
• gestational diabetes
• possibly reduce the risk of miscarriage
• contributes to the regulation of placental inflammation.  
• reduce the risk of autism, both in animal and human studies

Importantly vitamin D therapy has also been shown to improve symptoms in children with autism and reduce the risk of autism.  The benefit of vitamin D may be related to the duration of supplementation with some studies showing benefit when vitamin D is started a year before pregnancy.  

There is ample and compelling evidence that a blood level of 40-60 ng/mL (or even 40-80) is necessary for optimal health.  The benefits of Vitamin D are probably both short term and long term, but maximal benefit undoubtedly requires maintaining vitamin D > 40 ng/ ml over an extended period.   In the absence of adequate sun exposure, 1,000 -2000 IU vitamin D daily for children is required to achieve these levels.  Others recommend  that pregnant young children receive 150 IU/kg/day and also have 25(OH)D levels checked every 3 months.  

Historically, 400 IU (10 ug) of vitamin D has been recommended because it closely approximated the amount of vitamin D in a teaspoonful of cod liver oil. However, this is inadequate for most people.  Vitamin D can be provided with pills, mouth spray, or skin patch.  Vitamin D3 (cholecalciferol) is the type that most experts believe should be favored over vitamin D2 (ergocalciferol), so also watch for that in the label.  

Adults found to be vitamin D deficient should take either 50,000 IU of vitamin D3 per week or 6000 IU per day for 8 weeks to achieve a serum 25(OH)D level of 30 ng/mL. The Endocrine Society's guidelines support this recommendation but add that a maintenance dose of 1000 IU per day may be needed to consistently raise serum 25(OH)D levels above 30 ng/mL in patients aged 1 to 18 years and as much as 1500 to 2000 IU per day in patients aged 19 to 50 years (and presumably more for those older than 50).   Patients with malabsorption syndromes, with obesity, or taking medications that affect vitamin D metabolism, maintenance doses may need to be between 3000 and 6000 IU daily.   

The best way to determine your Vitamin D requirements is to individualize, based on your diet, sun exposure (altitude, amount of ozone, time of day, type of skin etc) and your individual vitamin D levels.  You can do all of this through apps like 'dminder'.   I would recommend visiting their website at  https://grassrootshealth.net   ( GrassrootsHealth is a nonprofit public health research organization dedicated to moving public health messages regarding vitamin D from research into practice).   Also consider registering for their study and complete their health questionnaire (I have no financial interest in grassrootshealth.net or their products).  In the UK, there are a number of low cost home tests available, offered as low as £ 29.   

 
Pregnancy. There is compelling evidence that all women should have their vitamin D level checked  early in pregnancy, and ideally 1-2 more times during pregnancy.  The first time should come right after the positive pregnancy test itself.  Vitamin D supplementation is very important for pregnancy, regardless of your level, but your level can determine how much Vitamin D you should take.  A good maintenance dose during pregnancy is 1000-2000 IU/ ml but if you are vitamin D deficient, a daily dose of 4000-6000 IU/ ml is recommended.     Vitamin D supplementation of 4000 -6000 IU/day is recommended during pregnancy while others suggest all pregnant and lactating women receive 5000 IU/day.  Notice this amount is much higher than you will get with a multivitamin and 10 x the usual recommended dose in non pregnant patients.  However, don't be intimidated.  Doses up to 10,000 IU/ day are considered safe and there have been no adverse effects associated with this higher dosage.  It turns out we have been under-supplementing ourselves for decades and at the same time we've seen autism rates and other conditions increase.   

 Vitamin D and omega-3s may work together.    By taking simple dietary steps like increasing your consumption of foods or supplements rich in the omega-3 fatty acids EPA (eicosapentaenoic acid) and DHA (docosahexaenoic acid), your Omega-3 Index will rise.  However, similar to vitamin D serum level response to supplementation, there is a wide variation in response between omega-3 intake and a resulting Omega-3 Index level; there is no way to tell if you are getting enough omega-3s unless you test your levels.  

The Omega-3 Index is a blood test that measures the amount of omega-3 fatty acids (EPA and DHA) in red blood cell (RBC) membranes and is expressed as a percent of total RBC fatty acids. It is a long-term and stable marker of omega-3 status, and it reflects tissue levels of EPA+DHA.

An Omega-3 Index of over 8% is associated with the lowest risk of death from heart disease and below 4% with the highest.

In a scientific analysis of 446 compounds regarding the ability to boost the innate immune system, two were discovered which stood out, the resveratrol present in red grapes and a compound known as pterostilbene in blueberries. Both resveratrol and pterostilbene, which are known as stilbenoids, worked synergetically with vitamin D and had a considerable effect in elevating the expression of the CAMP gene (human cathelicidin antimicrobial peptide), which plays a part in immune function.

Resveratrol continues to be the topic of many studies for a variety of possible health benefits, from fighting cancer to improving cardiovascular health and reducing inflammation. This study shows a clear synergy with vitamin D which increased CAMP expression by a number of times. 

 The CAMP gene itself is also the subject of much study, as it has been shown to play a key role in the “innate” immune system, the body’s ability to fight bacterial infection and the 1st line of defense. A strong link has been proven between function of the CAMP gene and adequate vitamin D levels, and this study indicates that certain other compounds could be involved as well. 

 The stilbenoids which fight infections are compounds made by plants, and appear to impact some of the signaling pathways that enable vitamin D to perform its job. It seems that combining these compounds together with vitamin D has significantly more impact than any of them would have separately. 

The B vitamins are important for conversion of food to energy.  

Folate (Vit B9)   deficiency in folate is quite common and can contribute to irritability and depression. Numerous studies support the importance of folate for improving mood. Folate levels are lower in depressed individuals and a deficiency of folate has been shown to lower levels of serotonin as well as cause fatigue. It's also incredibly essential during pregancy to improve

• preeclampsia  
• growth of the placenta, synthesis of DNA and the development of the baby
• Essential for red blood cell production and helps prevent forms of anemia
• Possibly reduce the risk of miscarriage
• Possibly reduces the risk of preterm delivery

Taking folate during your pregnancy is not an option- it's a necessity!  It is one of the few things you can do that can actually affect the outcome of your pregnancy!  400 mcg/day of folate is recommended during pregnancy, ideally beginning before conception.   It should be noted that the neural tube closes by the 28th day of conceiving and so many females may not even know that they are pregnant before the neural tube normally closes. 

Vitamin B12  Aids folate metabolism In Pregnancy  

• Essential for baby’s neural tube formation, brain and spine development
• Together with Folate (B9), it works to produce DNA synthesis and red blood cells
• Aids the development and functioning of your brain, nerves and blood cells
• Helps improve your energy, mood and stress levels by aiding the metabolization of fats, carbohydrates, and proteins.
• Helps maintain the normal central nervous system and neurological 

Vitamin B6 helps fertility and ovulation. 

Vitamin E protects against cell damage from free radicals.  Also promotes healthy heart and circulation

Co enzyme Q10.  Involved in production of energy.