A client brings in blood results from their GP. Vitamin D: 48 nmol/L. Reported as normal. They have fatigue, low mood, recurrent infections, muscle aching, and difficulty concentrating. Their GP has suggested they may be slightly stressed.
48 nmol/L (19 ng/mL) is above the UK threshold of 25 nmol/L (10 ng/mL), so it is reported as normal. It is just under the 50 nmol/L (20 ng/mL) that the US Institute of Medicine judged enough for bone health in at least 97.5% of people (Ross 2011). Whether it explains this client’s fatigue or low mood is a separate question, and the trial evidence on that is weak.
More fundamentally: 48 nmol/L of 25-hydroxyvitamin D (the storage form measured by a standard blood test) tells you what is in storage. It tells you nothing about conversion to the active hormonal form, nothing about whether that conversion is proceeding normally, nothing about how sensitive the vitamin D receptor is in this person's tissues, and nothing about the magnesium and K2 status that determines whether the converted D is being directed appropriately. It is one data point in a system with multiple variables, and it is being treated as the whole story.
What 25-OH-D actually measures — and what it doesn't
Vitamin D operates through a two-step conversion sequence before it has any biological effect. Understanding this sequence is not an optional detail. It is the clinical argument for why a blood test that returns a "normal" 25-OH-D result can coexist with genuine functional insufficiency.
Why that first step is so limited in Scotland, and how skin tone changes it, is in Skin Tone, Latitude, and Why Vitamin D Advice Fails in Scotland.
Why vitamin D does far more than bones
The public understanding of vitamin D is almost entirely framed around bone health — calcium absorption, rickets, osteoporosis prevention. That is the part with the strongest evidence. Vitamin D receptors are found in most cell types, which is why researchers have looked at much more than bone.
How sure is this? The six areas above are mechanisms and associations. Low vitamin D goes with many problems in observational studies, but in VITAL, a trial of 25,871 adults who weren’t selected for deficiency, vitamin D did not lower cancer or heart and stroke events (Manson 2019). The US Institute of Medicine found the evidence for benefits beyond bone “inconsistent” and “insufficient to inform nutritional requirements” (Ross 2011).
The reference range problem — again
The UK threshold is 25 nmol/L (10 ng/mL), set by the Scientific Advisory Committee on Nutrition as the level below which risk to bone and muscle health rises; SACN says it is not a diagnostic threshold for disease (SACN 2016). The US Institute of Medicine used 50 nmol/L (20 ng/mL) for bone (Ross 2011). The Endocrine Society’s 2011 guideline, written for patients at risk of deficiency, suggested aiming above 75 nmol/L (30 ng/mL) (Holick 2011). Its 2024 guideline found “no clear evidence defining the optimal target level” and suggested against routine testing in healthy adults (Demay 2024). These thresholds were set for bone; whether higher levels help immunity, mood or blood sugar is the open question.
Vitamin D levels: what the guidelines say, and how sure they are
| 25-OH-D Level | UK status | What the guidelines say | How sure |
|---|---|---|---|
| Below 25 nmol/L (10 ng/mL) | Deficient | Treat (SACN 2016) | Strong for bone: risk of rickets and osteomalacia rises. A clinical priority. |
| 25–50 nmol/L (10–20 ng/mL) | Above the UK threshold | Below the US bone target of 50 (Ross 2011) | Bone: worth correcting. Other symptoms: linked in observational studies; trials are mixed. |
| 50–75 nmol/L (20–30 ng/mL) | Normal | Enough for bone in at least 97.5% of people (Ross 2011) | The Endocrine Society’s 2011 guideline called this “insufficiency” for at-risk patients; its 2024 guideline found no clear evidence for a higher target. |
| 75–150 nmol/L (30–60 ng/mL) | Normal | Above the 2011 Endocrine Society target | No trial shows extra benefit from getting here if you weren’t deficient. VITAL’s participants averaged 77 nmol/L at the start (Manson 2019). |
| Above 150 nmol/L (60 ng/mL) | High | Caution warranted | No established benefit above this level for most people. Risk of hypercalcaemia with prolonged very high supplementation. Requires clinical justification and monitoring. |
What needs to be in place for vitamin D to work properly
Vitamin D does not act alone. The full mineral regulatory system — calcium, magnesium, phosphate, PTH, and K2 — must be operating correctly for vitamin D to be converted efficiently and directed appropriately. Two cofactors deserve particular attention.
Magnesium is required for vitamin D activation (both hydroxylation steps), for VDR function, and for the enzymes involved in vitamin D metabolism. Supplementing vitamin D without adequate magnesium is like pressing the accelerator with the engine oil warning light on. The conversion happens poorly, and some of the downstream signalling is impaired. That is mechanism; it hasn’t been tested as an outcome trial.
Vitamin K2 directs calcium to bone and teeth rather than to soft tissues and arterial walls. High-dose vitamin D increases calcium absorption significantly. Without adequate K2, that calcium may deposit in arteries rather than bones — the mechanism behind concerns about vitamin D supplementation in isolation. Food-based K2 (fermented dairy, natto) or K2 as MK-7 alongside D3 is common practice, but it is based on mechanism; trials haven’t shown that adding K2 changes outcomes for people taking ordinary doses of vitamin D.
"Vitamin D is a hormone precursor operating within a mineral regulatory system. Treating it as a standalone supplement — a number to raise, a capsule to take — misses the clinical picture almost entirely."
The individual variation principle
Every principle in this post comes with the same caveat: individual variation is real, significant, and clinically relevant. Two people with identical 25-OH-D results may have very different functional vitamin D status depending on their VDR genetics, their kidney conversion capacity, their magnesium status, their inflammatory load, and their baseline requirements. A result that represents functional sufficiency for one person may represent functional insufficiency for another.
This is why the clinical position on vitamin D is not "everyone needs a specific dose" or "everyone needs a specific level." It is: test first, address the cofactors, supplement to functional sufficiency confirmed by retesting, and adjust based on individual response. The target range is a guide. The individual data is the clinical reality.
Sources
- Scientific Advisory Committee on Nutrition. Vitamin D and Health. 2016. gov.uk
- Ross AC et al. The 2011 IOM report on dietary reference intakes for calcium and vitamin D. J Clin Endocrinol Metab 2011;96:53–58. PMID 21118827. doi:10.1210/jc.2010-2704
- Holick MF et al. Evaluation, treatment and prevention of vitamin D deficiency: Endocrine Society guideline. J Clin Endocrinol Metab 2011;96:1911–1930. PMID 21646368. doi:10.1210/jc.2011-0385
- Demay MB et al. Vitamin D for the prevention of disease: Endocrine Society guideline. J Clin Endocrinol Metab 2024;109:1907–1947. PMID 38828931. doi:10.1210/clinem/dgae290
- Manson JE et al. Vitamin D supplements and prevention of cancer and cardiovascular disease (VITAL). N Engl J Med 2019;380:33–44. PMID 30415629. doi:10.1056/NEJMoa1809944
- Jolliffe DA et al. Vitamin D supplementation to prevent acute respiratory infections: updated systematic review and meta-analysis. Lancet Diabetes Endocrinol 2025;13:307–320. PMID 39993397. doi:10.1016/S2213-8587(24)00348-6
- Tian XQ, Chen TC, Matsuoka LY, Wortsman J, Holick MF. Kinetic and thermodynamic studies of the conversion of previtamin D3 to vitamin D3 in human skin. J Biol Chem 1993;268(20):14888–92. PMID 8392061. PubMed (mechanistic).
Vitamin D is one of 57 to 87 markers on the TDG blood chemistry panel
Interpreted alongside magnesium, calcium, PTH, inflammatory markers, and the full metabolic picture — so the number makes clinical sense rather than being read in isolation. The full vitamin D story, including what drives insufficiency in this specific person, requires the full clinical picture.
See the TDG Programme →