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Let's Get Personal: These 10 Factors Mediate Your Individual Response To Vitamin D

Ashley Jordan Ferira, Ph.D., RDN
mbg Vice President of Scientific Affairs
By Ashley Jordan Ferira, Ph.D., RDN
mbg Vice President of Scientific Affairs
Ashley Jordan Ferira, Ph.D., RDN is Vice President of Scientific Affairs at mindbodygreen. She received her bachelor's degree in Biological Basis of Behavior from the University of Pennsylvania and Ph.D. in Foods and Nutrition from the University of Georgia.
Image by LUCAS OTTONE / Stocksy
September 24, 2021

We are unique individuals with the DNA to prove it. As it turns out, your response to vitamin D can be influenced by a variety of personal factors, from our genes and sex to age, dietary pattern, and much more. I think it's time to get personal, for the sake of our nation's vitamin D health.

If you're providing your body with sufficient vitamin D3 (5,000 I.U. plus per day) from a high-quality D3 supplement (or via a combination of food, sunshine, and supplement) to overcome personal nuance in vitamin D metabolism and response, then you're probably fine [you can know for sure by having your doc test your 25(OH)D level].* 

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But just in case your journey to achieve vitamin D sufficiency hasn't been so straightforward, here are some factors you'll definitely want to consider:

1. Your starting point (baseline status)

Where you start affects where you'll end up. I'm talking about your baseline nutrition status. The more pronounced your hypovitaminosis D dilemma (i.e., how insufficient or deficient you are) is to start, the more effective and responsive you will be to supplementation.* 

This repletion phenomenon is documented with most nutrients and repeatedly demonstrated in the clinical research for vitamin D. Remember, that vitamin D insufficiency [25(OH)D less than or equal to 30 ng/ml] and deficiency [25(OH)D less than or equal to 20 ng/ml] are territory you'll want to avoid.

2. Frequency of input

Vitamin D is an essential fat-soluble micronutrient. It's essential today, tomorrow, and always and thus requires daily input. Because vitamin D is truly scant in naturally occurring and fortified foods, and sun exposure is variable at best (and carries certain obvious risks), supplementation with a high-quality, high-potency D3 supplement is the most prudent approach to guarantee reliable, daily D3 input. 

If your vitamin D approach is more laissez-faire and sporadic, your vitamin D status will suffer. You'll yo-yo in and out of suboptimal vitamin D status, or swing into deficient states even. This has broad health implications for your bones, muscles, immunity, neurological function, cardiometabolic health, and more.* I strongly recommend intentionality and establishing a daily ritual with this particular nutrient.

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3. Your body composition

I'd like to start off by saying I am 100% pro-body-positivity and think overall health is a holistic concept that cannot and should not be boiled down to a singular feature of someone's body composition. With that said, vitamin D is a fat-soluble nutrient. That's its chemical makeup. As such, it is attracted to and sequestered in adipose (fat) tissue. Research indicates that there may also be a dilution factor and even metabolic differences for key vitamin D pathways when higher adiposity is involved.

And this science is very clear: An inverse relationship exists between adipose tissue and vitamin D status. In other words, the more adipose tissue (as measured by BMI, waist circumference, fat percentage, etc.), the lower your circulating vitamin D levels 25(OH)D. Furthermore, clinical consensus estimates that vitamin D needs for people with overweight or obesity may be two to three times higher to compensate for the aforementioned variables.


4. Sex

Well, these next two personal factors are kind of annoying since you can't control them. But alas, women have repeatedly been seen in clinical research to have lower vitamin D levels (worse vitamin D status) than men. The biological and environmental underpinnings for this difference are not abundantly clear.

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5. Age

When it comes to age, the mechanisms for depressed vitamin D levels are more lucid. First, cutaneous synthesis (i.e., when sunshine hits exposed skin and creates vitamin D3) is reduced as we age into older adulthood and beyond. Next, conversion of the circulating 25(OH)D form to its active, doubly hydroxylated 1,25(OH)2D form (the active hormone version of vitamin D) is blunted. 

Combined with potential medication interactions and environmental factors (less food consumption and outdoor activities), older age is a major vitamin D deficiency risk factor to be mindful of, for yourself and your loved ones.

6. An ineffective (or no) vitamin D supplement

If you're not taking a vitamin D supplement (or vitamin-D-containing supplements, like a multivitamin, bone, or immune complex), your likelihood of vitamin D deficiency is high. Perhaps this compelling science will inspire you to reconsider vitamin D supplementation. 

And if you are taking a vitamin D supplement daily (since adherence is directly tied to its success), is it working? When investing in a vitamin D supplement, I like to make sure it is:*

  1. The correct form (hello, D3). Vitamin D3 (cholecalciferol) has superior bioefficacy, bioactivity, and stability than vitamin D2 (ergocalciferol). It's time D2 received a demotion.
  2. An effective potency (3,000 is minimum; 5,000 I.U. is ideal)
  3. Thoughtful enough to optimize fat solubility for absorption (with built-in healthy fats)
  4. Sourced from a premium organic, plant-origin D3 source (like sustainable algae)
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7. Exogenous sources: sunshine

The next two factors may seem obvious but actually merit attention. If your vitamin D intake from your diet plus sunshine isn't cutting it (see here for why it probably isn't), then your need for vitamin D supplementation (and likely your response to it) will be heightened.

If you're "sun challenged" (um, most of us these days), that means less vitamin D3 production via your skin. And when I say relying on sun exposure for vitamin D sufficiency throughout life is dicey at best, hear me out. 

Banking on sun for D is so variable, including but not limited to: regularity of time spent outdoors, amount of clothing, sufficient skin surface area exposed, skin tone (with darker skin tones requiring more sun exposure), season (with fall and winter majorly limiting D opportunities from the sun), latitude or distance from the equator, pollution, UVB range, and angle hitting your skin, etc.

8. Exogenous sources: food

Stat: 93% of U.S. adults aren't consuming a measly 400 I.U. of this fat-soluble nutrient per day (even counting fortified foods). While "food first" genuinely fails us with this particular nutrient, dietary pattern also comes into play with opportunities (or lack of) to consume vitamin D.

For example, individuals who avoid dairy due to lactose intolerance, vegan practice, or otherwise, are missing a key fortified source of vitamin D (granted, only 100 I.U. per 8 ounces of milk). And if your dietary pattern doesn't include seafood (specifically oily fish like salmon, anchovies, trout, etc.), then you're missing the top naturally occurring sources of vitamin D3 that Mother Nature provides.

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9. Your DNA

Just like many health-related issues, our DNA comes into play. Our unique genotype includes genetic polymorphisms specific to vitamin D's metabolism, transport, and receptor binding. This DNA variability sprinkles individual differences into our response to vitamin D supplementation. 

For example, we know that single nucleotide polymorphisms (SNPs) affect vitamin D metabolism. Serum 25(OH)D levels can be influenced by genetic differences in the vitamin D binding protein (VDBP) per gene rs2282679. (The G allele is tied to lower vitamin D levels.) 

If your VDBP levels are higher, more 25(OH)D will be bound and less available to do its job. Thus, your supplementation needs may be higher. You can ask your health care provider to measure "free 25(OH)D" to quantify the unbound vitamin D in your blood, but this test is used more in research and is not yet commonly measured in clinical settings.

Two key SNPs related to 25-hydroxylase (rs10751657, CYP2R1) and 1α-hydroxylase (rs10877012, CYP27B1) have also been identified. These are the enzymes that convert vitamin D into its circulating form and active hormone form, respectively.

And then FokI (rs2228570), BsmI (rs1544410), ApaI (rs7975232), and TaqI (rs731236) are genetic polymorphisms linked to the vitamin D receptor (VDR) and thus the ability of vitamin D to bind and do its many critical jobs in the body.*

These genetic differences (and their risk associations for key health pathways) are still in the rapidly growing clinical research stage, with everyday implications for clinical practice forthcoming. With that said, an integrative-minded health care practitioner on the cutting edge may consider SNPs in a personalized nutrition assessment and treatment approach.

10. Suboptimal GI absorption or downstream metabolism

Last but certainly not least are any individual differences or anomalies in physiology that affect the gastrointestinal tract (i.e., vitamin D's absorption starting point), liver [where vitamin D is converted to 25(OH)D], or kidneys [where 25(OH)D is predominantly converted to its active form of 1,25(OH)2D]. 

In other words, if the absorption or metabolism of vitamin D is attenuated, then your supplement approach will need to compensate accordingly. And in these cases, you'll definitely want to partner with your health care practitioner for personalized supplementation consideration.

The takeaway.

Every person is unique (and so is their response to vitamin D). Individual factors can affect your response to vitamin D inputs, whether via consumption or UVB exposure. From baseline vitamin D status and body fat percentage to our genes and more, personal facets affect your vitamin D supplementation dosing and response. Now you know the full lineup of potential mediators, including the efficacy of your vitamin D supplement itself.*

If you are pregnant, breastfeeding, or taking medications, consult with your doctor before starting a supplement routine. It is always optimal to consult with a health care provider when considering what supplements are right for you.
Ashley Jordan Ferira, Ph.D., RDN
Ashley Jordan Ferira, Ph.D., RDN
mbg Vice President of Scientific Affairs

Ashley Jordan Ferira, Ph.D., RDN is Vice President of Scientific Affairs at mindbodygreen. Ashley received her B.A. in Biological Basis of Behavior from the University of Pennsylvania and Ph.D. in Foods and Nutrition from the University of Georgia. Her research contributions span weight management, bone health, and vitamin D. Ferira is a nutrition scientist and dietitian with experience in nutrition product development, medical affairs, communications, and SEO writing for global firms, including Nature Made, Metagenics, and Three Ships.

In addition to her mindbodygreen contributions, Ferira is published in Health, Remedy Review, Metagenics Institute, American Family Physician, The Journal of Clinical Endocrinology & Metabolism, and Osteoporosis International. She has a passion for the translation of evidence-based science into products and information that help people lead healthier lives. She is a believer in compassionate, informed, and personalized approaches to nutrition and health care. Ashley lives in beautiful Charleston, South Carolina, where she was born and raised. Whether savoring an orchestral performance or delectable meal at a local restaurant, you will find her enjoying Charleston’s cultural and culinary arts with family and friends.