Vitamin D is critical for health. Virtually every cell in the body has a vitamin D receptor, which, when bound to vitamin D, can influence the expression of more than 200 genes (1, 2). Vitamin D promotes calcium absorption in the intestine and maintains calcium and phosphate levels in the blood, protecting against osteoporosis, rickets, and bone fracture (3, 4). It also regulates immune function, cell growth, and neuromuscular function (5, 6).
With the many roles that vitamin D plays in the body, deficiency of this fat-soluble vitamin is a real cause for concern. Vitamin D deficiency has been found to increase the risk of heart attack, cancer, diabetes, asthma, and autoimmune disease (7, 8, 9, 10, 11, 12). Our modern indoor lifestyle limits our sun exposure, and we can only get a small amount of vitamin D from diet (13). According to the lower boundary of the U.S. lab range of 30 ng/mL, as many as 70 percent of Americans are considered deficient (14, 15).
It’s great that awareness about vitamin D deficiency is increasing, with more doctors than ever testing vitamin D levels. However, like many nutrients, vitamin D follows a U-shaped curve, meaning that both low levels and very high levels are associated with negative health outcomes (16). Unfortunately, few practitioners are aware of the dangers of vitamin D toxicity, and many just test serum vitamin D once and recommend a daily 5,000 or 10,000 IU supplement to their patients.
In this article, I’ll discuss the risks of over-supplementation, why you should get most of your vitamin D from sunlight, and the reasoning behind my current approach to vitamin D.
Risks of Excess Vitamin D Supplementation
But a large body of evidence in the medical literature strongly suggests that optimal vitamin D levels might be lower than these figures. There is little to no evidence showing benefit to 25(OH)D levels above 50 ng/mL, and increasing evidence to suggest that levels of this magnitude may cause harm. Consequences of vitamin D toxicity include heart attack, stroke, kidney stones, headache, nausea, vomiting, diarrhea, anorexia, weight loss, and low bone density (18).
Furthermore, in most studies, taking vitamin D supplements does not decrease risk of death, cardiovascular disease, or other conditions. Based on an exhaustive review of over 1,000 studies in 2011, the Institute of Medicine recommends a much more conservative range of 20 to 50 ng/mL (19).
Some research on Israeli lifeguards suggests that, contrary to popular belief, vitamin D toxicity from sunlight alone (in the absence of supplementation) is possible (20). That said, it is much more difficult to achieve toxic levels through sun exposure alone. Sunlight is the optimal source of vitamin D, and has numerous benefits above and beyond improving vitamin D status.
Beyond Vitamin D: The Many Benefits of Sunlight
Vitamin D is really just the tip of the iceberg when it comes to the benefits of sunlight. A recent 20-year study following 29,518 subjects found that those individuals avoiding sun exposure were twice as likely to die from all causes (21). While this study did not assess vitamin D levels, findings from other epidemiological studies suggest that this cannot be accounted for by the increase in vitamin D production alone.
Indeed, humans make several important peptide and hormone “photoproducts” when our skin is exposed to the UVB wavelength of sunlight (22). These include:
- β-Endorphin: a natural opiate that induces relaxation and increases pain tolerance (23, 24)
- Calcitonin Gene-Related Peptide: a vasodilator that protects against hypertension, vascular inflammation, and oxidative stress (25)
- Substance P: a neuropeptide that promotes blood flow and regulates the immune system in response to acute stressors (26)
- Adrenocorticotropic Hormone: a polypeptide hormone that controls cortisol release by the adrenal glands, thus regulating the immune system and inflammation (27)
- Melanocyte-Stimulating Hormone: a polypeptide hormone that reduces appetite, increases libido, and is also responsible for increased skin pigmentation (27)
Exposure to the UVA wavelength of sunlight has also been shown to have benefits, including increasing the release of nitric oxide from storage (28). Nitric oxide is a potent cellular signaling molecule that dilates the blood vessels and thus reduces blood pressure (29).
Optimal Vitamin D Range Depends on Many Factors
So how much do you need? At the first annual IHH-UCSF Paleo Symposium in San Francisco this year, nutritional biochemist Dr. Chris Masterjohn summarized evidence suggesting that optimal vitamin D levels may vary from population to population, despite the fact that there is currently only one reference range used for all patients.
Ethnicity is one major consideration. For example, black people have lower 25(OH)D than white people in the U.S., yet they typically have much higher bone mineral density. Furthermore, non-Caucasians have lower 25(OH)D levels than Caucasians, even at their ancestral latitudes (32). From these and other studies, it has been suggested that people with non-white ancestry may be adapted to a lower optimal 25(OH)D level than people with white ancestry.
Another factor that influences toxicity is nutritional status. The fat-soluble vitamins A, D, and K work synergistically, and adequate vitamin A and K may protect against toxic effects of excess vitamin D (33). Sufficient levels of potassium and magnesium have also been suggested to protect against vitamin D toxicity (34). Unfortunately, most people have nutrient deficiencies in these micronutrients in the developed world, making them more susceptible to vitamin D toxicity.
What about optimal vitamin D range from an evolutionary perspective? A study on traditionally living hunter–gatherer populations in East Africa found that the Masai and Hadzabe had average 25(OH)D concentrations of 48 ng/mL and 44 ng/mL, respectively (35). These indigenous populations get a great deal of sun exposure but also have very high intakes of vitamins A and K, suggesting that these levels are probably towards the higher end of the optimal range for most people in the modern world.
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Using Parathyroid Hormone Levels to Individualize Vitamin D Testing
As we saw in the last section, 25(OH)D lab ranges should vary by population, genetics, and nutritional status. In the absence of specific ranges, we need other biological markers that can help to clarify vitamin D status. To find these biological markers, we need to look at how vitamin D is metabolized.
When UVB contacts the skin epidermis, vitamin D is produced from 7-dehydrocholesterol. This vitamin D then travels in the blood to the liver, where it undergoes primary hydroxylation (the addition of a hydroxyl group, consisting of one oxygen and one hydrogen atom) on the 25th carbon atom. The result is 25(OH)D, which is the metabolite most widely used to assess nutritional vitamin D status. This compound circulates in the blood until it undergoes secondary hydroxylation on the first carbon atom in the kidney, resulting in 1,25(OH)2D, the active form of vitamin D (36).
You might be wondering: why don’t we test the active form? While certainly informative, the amount of active vitamin D is not directly reflective of nutritional vitamin D status because the secondary hydroxylation step is tightly regulated by parathyroid hormone (37). When the parathyroid glands sense a drop of blood calcium levels, they secrete parathyroid hormone (PTH). PTH stimulates the formation of active vitamin D, which increases calcium absorption in the small intestine and calcium release from bone in an attempt to restore normal blood calcium levels (38).
With a basic understanding of this pathway, we can use PTH, calcium, and active vitamin D3 as markers to give us a more complete picture of someone’s vitamin D status. In his presentation at IHH-UCSF, Dr. Masterjohn suggested that serum PTH levels above 30 pg/mL may be indicative of biological vitamin D deficiency when 25(OH)D levels are borderline low. Conversely, if 25(OH)D levels are borderline low or even slightly below the laboratory reference range (e.g., 25 to 30 ng/mL), but PTH is less than 30 pg/mL, it is unlikely that the patient is vitamin D deficient, and supplementation is not warranted.
Instead of focusing on the 25(OH)D level itself, what we really want to achieve is maximum suppression of PTH levels for optimal calcium homeostasis and bone health. Beyond this level, more vitamin D is not necessarily better.
Conclusion
Based on my assessment of the literature and my own clinical experience, I believe the functional range for 25(OH)D is around 35 to 60 ng/mL. However, I can’t stress enough that there is significant variation among populations. For those with non-white ancestry, the optimal range may be a bit lower. For those with autoimmune disease, the optimal range might be a bit higher (45 to 60 ng/mL) to maximize the immune-regulating benefits of vitamin D. Here are a few recommendations for optimizing your vitamin D level.
- Don’t supplement blindly.
If your 25(OH)D level is:
- less than 20 ng/mL: you likely need some combination of UV exposure, cod liver oil, and a vitamin D supplement
- 20 to 35 ng/mL: get your PTH tested. If PTH is adequately suppressed (less than 30 pg/mL), supplementing is probably unnecessary.
- 35 to 50 ng/mL: continue your current diet and lifestyle for maintaining adequate vitamin D
- greater than 50 ng/mL: try reducing your vitamin D supplements, and make sure you are getting adequate amounts of the other fat-soluble vitamins to protect against toxicity
- Get retested!
Check your levels after three to four months to see if you have achieved or maintained adequate levels of vitamin D. If not, adjust your diet, lifestyle, or supplements accordingly and check again in another three to four months.
- Get sunlight or UV exposure as your primary form of vitamin D.
Reap the many benefits of sunlight beyond just subcutaneous production of vitamin D, and reduce your chance of achieving toxic levels. Spend about 15 to 30 minutes, or about half the time it takes your skin to turn pink, in direct sunlight. Sunscreens not only block production of vitamin D, but also all of the other beneficial photoproducts produced in the skin in response to UVB. - Mind your micronutrients to protect against toxicity.
Try cod liver oil as a good source of vitamins A and D and high-vitamin butter oil or pastured butter and ghee for vitamin K. Sweet potatoes, bananas, plantains, and avocados all contain significant amounts of potassium. Consider supplementing with magnesium as it is very difficult to get adequate amounts of this micronutrient from food due to soil depletion.
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In a book “Death by Calcium” by Dr. Thomas E Levy MD, JD, it says one should never have combined Calcium & Vitamin D supplements
How about this research about probiotics?
It seems like they might not be as useful as we think.
https://www.cell.com/cell/fulltext/S0092-8674(18)31108-5
Thanks for highlighting this study and putting the link to it. Interestingly the human volunteers were instructed not to have probiotics one month prior to the study. If identical probiotics were administered to volunteers who had been taking probiotics prior to the antibiotics, I wonder how much these probiotics would subsequently inhibit the indigenous microbiome diversity.
It seems that reduced biodiversity enhanced and prolonged dysbiosis. I also wonder how reducing the clostridia species affected the volunteers.
Hi Chris,
I am at my wits end. I am deficient in D ( last level was 22 ).
But I just cannot tolerate D supplements. I’ve tried 25 different brands and types, with co factors, without co-factors. I’ve tried vegan, CLO, liquid…… all make me feel SO much worse. I have so many symptoms of D deficiency but just can’t handle supplementing. I mean it gets really bad, to the point I feel like I may die.
Do you have any idea why?
PTH and calcium levels are normal.
I should add, this even happens with doses as low as 400IU.
Biotech Pharmacal do a dry powder water soluble form of vitamin d3 that can be added to foods/drinks.
The fine white powder in the capsules can be put into recipes you are preparing.
I make my own plain yoghurt and always add the contents of a Biotech pharmacal capsule to ensure each yoghurt comes complete with a small amount of vitamin D3.
You can add vitamin d3 powder to cake/biscuit, cookie mixtures before they are baked or to home made ice-cream before it is frozen.
The powder can be added to drinks as well.
It could be that providing vitamin d in small amounts incorpoated in the meals and drinks you consume through the day builds up your tolerance.
You don’t say if you have tried topical application.
Vitamin d drops or vitamin d creams can be applied to the skin and the absorption rate is comparable to the oral route.
“Topical Delivery of Vitamin D3: A Randomized Controlled Pilot Study”
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3976443/
It’s possible that vitamin d is having a direct impact on the pathogens in your digestive tract and the die off of gram negative bacteria and candida is making you fill ill. Using vitamin d topically may solve the problem.
Thank you Ted. Will try this.
Pam, I wonder if you and Lena have the same situation going on which affected me for many years before I finally figured it out. That is that although my D25 blood test always showed I was deficient in D, I was actually too high. It was not until I had both my D25 and D1,25 levels tested that I found out my total D levels were too high. Doctors assume that if your D25 levels are low, your total D levels will also be low, but this is not true for many people. When testing for D1,25 Quest is a better lab than Labcorp, and the blood sample must be frozen and stay frozen until testing. https://mpkb.org/home/tests/dtesting
I almost died of vitamin D toxicity and still have not recovered from the neurological damage caused by vit D overdose. No matter how much vit D3 i took my D25 test was always low. After five years of 10,000 units per day my vit D was raised from 9 to 12. Meanwhile my D1,25 was skyrocketing. I wish i had listened to my body instead of my doctor on this and encourage you to do the same. The only way to know if you need to supplement with vitamin D is by testing both D25 and D1,25 levels.
I’m curious if you have regularly measured the serum calcium (and perhaps PTH). The body protects itself from too high serum calcium levels and since D25 aids in absorption/retention of calcium it seems the body will shunt it to D1,25 to protect itself from this. (D25 being storage, and D1,25 being active might be confusing terminology.) One of the reasons this might happen is due to a benign growth (adenoma) on one of the parathyroid glands, which can lead to an increased and inappropriate secretion of parathyroid hormone (PTH), which primarily controls that absorption/retention of calcium (and phosphorus) into the blood to maintain optimium levels. The PTH should approach near zero if the serum calcium is above what the body prefers. If it elevates regardless of the serum calcium it might cause the serum calcium to also elevate even higher. So, taking any vitamin D3 at that point might contribute to pushing the serum calcium even higher, and the body might refuse to shift the D1,25 back to D25 to reduce absorption/retention of any more calcium.