Hypothesis: Does Vitamin D "Deficiency" Protect Us From Phosphorus Overload? 1,25OHD Production Drops by 19pg/dL With Each 1mg/dL Increase in Phosphorus

Image 1: Did you ever take into consideration that your body may refuse to produce vitamin D with good reason?

Do you know that? You have an idea, a hypothesis, a stroke of genius, but for whatever reason you don't have access or time to do some research to probe it!? For me that was the case with my "phosphorus <> vitamin D" hypothesis. And in view of the fact that I started to ignore the dozens of weekly papers on the great importance vitamin D, by the means of which their authors obviously hope get their share of the sudden media attention, it took a more or less unrelated post by Mallory Pazdersky on Highbrow Paleo about the paradoxically low vitamin D levels of astronauts to remind myself that I wanted to do some research in this area... and what should I say? It did not take very long to find evidence in support of my theory.

Hypothesis: Our bodies reduce vitamin D to cope with the high phosphorus load in our diets

Don't get me wrong, I don't have the hubris to claim that this is the one and only explanation for the prevalence of "low" vitamin D levels in our society, but if you take a look at the experimental evidence from a 1986 study by Portale et al. (Portale. 1986; cf. figure 1), you will have to admit that the 1,25(OH) vitamin D levels (unfortunately similar data for 25OHD does not exist), you see in the "high phosphorus" weeks towards the end of the 30-day study period, in the course of which the subjects received diets that contained normal (1,300mg), low (<500mg/day) and high (3,000mg) amounts of dietary phosphorus, is highly reminiscent of the pattern the aforementioned busybodies are mourning in their papers.

Figure 1: Effects of restriction (<500mg/day, total) and supplementation (3,000mg/day) phosphorus on serum phosphorus and vitamin D levels in six healthy men (ages 26-40y); left- group average, right - individual response (Portale. 1986)

While the vitamin D levels of the the six health men (age 26-40y) hover at the lower end of the normal range in the "normal" diet phase, there is a rapid increase up to 65-75pg/dL in response to the reduced phosphorus intake in the "low phosphorus" phase of the trial (<500mg/day); an increase, which drove the vitamin D levels right to the top of the normal lab range. The high phosphorus diet (3,000mg/day), on the other hand, had the vitamin D levels plummet to a level hardly above what even official guidelines would consider full-blown deficiency.

Note: The rise in phosphorus and drop in vitamin D in the Portale study happened in the presence of adequate intakes of the phosphorus "antagonists" magnesium (350mg/day, which is 100mg more than the average American is getting from his / her diet; cf. Ervin. 2004) and calcium (850mg/day). In view of the the low(-ish) calcium and very low magnesium content of the standard Western diets, it does hence appear likely that we would see an even more pronounced increase in serum phosphorus levels and corresponding drop in vitamin D in the "average" American or European convenience food junkie.

In a subsequent paper published in the J. Clin. Invest. three years later Portale, Harris and Curtis revisited the topic and found that (Portale. 1989)

[w]hen these data are combined with those of our prior study [...] the relationship between serum levels of 1,25(OH)2D and 24-h mean serum levels of phosphorus is even stronger (r = -0.90, P < 0.001)"

According to these results, each 1 mg/dL increase in 24h phosphorus levels in your blood, will lead to a subsequent decrease in natural vitamin D by -19 pg/dL - even if all potential confounding variables remain constant (calcium intake, magnesium intake, dietary vitamin D, sun exposure, etc.)


Further evidence: Transient hyperphosphatemia with "normal-high" phosphorus intake

Figure 2: Effect of changes in dietary phosphorus within the normal range on the circadian rhythm in serum phosphorus concentration in normal men. After 8 days of high-normal (2,300 mg/d)or low-normal (625 mg/d) phosphorus intake (Portale. 1989).

What is makes things even more complicated, though, is that the phosphorus overload would probably remain undetected. This is a result of the circadian rhythmicity of serum phosphorus levels. As you can see in figure 2, the "fasted" or at least early morning blood test your local MD usually does will not detect the phosphorus overload, because even in the high phosphorus group serum phosphorus levels are "normal" (2.4 - 4.1 mg/dL) in the morning, but peak at 150% of the normal range in the early afternoon (cf.  figure 2 after the 2nd meal of the day at 12:30pm).

With respect to the underlying mechanism that could be responsible for this interaction between dietary phosphorus intake, serum phosphorus and calcitriol into its active form, Portale et al., speculate that (Portale. 1989)...

"the changes in extracellular concentration of phosphorus might effect changes in the activity of renal 1-hydroxylase" 

And guess what, 1-hydroxylase, which is also known as 25-Hydroxyvitamin D3 1-alpha-hydroxylase, does? Right! It is the enzyme that catalyzes the hydroxylation of the inactive to the active form of vitamin D and thus effectively controls your the concentration of 1,25(OH)2D3 (calcitrol) in your blood.

Question: Do low vitamin D levels protect against hyperphosphatemia?

Against that background it is at least thinkable that our bodies could lower the conversion of vitamin D3 (from skin or diet) into 25OHD, the "storage form" of D3, which is usually measured in blood tests and serves as a precursor to 1,25OHD, to minimize the absorption of dietary phosphorus to 60% (with normal to high levels, it would be >80%; cf. Hollick. 2007) and resort to the exuberant calcium stores in our bones to satisfy their calcium needs. After all, the potential increase in calcium absorption of higher calcitriol levels would be paid for dearly with an even higher influx of dietary phosphorus from the digestive tract and the potential of further leeching of calcium from the bones to reestablish the calcium to phosphorus ratio (Voet. 2004).

Eating no phosphorus at all is not a solution and probably not even necessary

If we now take into consideration that the reduction of phosphorus from a high-normal level of 1,300mg/day (which is identical to the intake of the avg. American in the year 1999-2000; cf.  Ervin. 2004), to 500mg/day did elicit a rapid and almost too pronounced increase to the top (and temporarily even beyond) the normal range, it stands to reason that even a reduction that would yield a ~1:1 calcium to phosphorus ratio, in other words, a phosphorus intake of roughly 900mg/day (identical to the US RDA), could help bring the vitamin D levels back up naturally.

Whether the combination of a low(er) dietary phosphorus load, adequate magnesium and potassium (another phosphorus antagonist intake that has become scarce in the typical Western diet), a reasonable amount of sun exposure and dietary vitamin D from whole foods, alone, will suffice to bring everyone's public vitamin D levels back up, and whether we do even want those levels to be in the >50pg/dL range, which is currently heralded as the lower end of the "optimal range" for serum vitamin D levels, does still have to be elucidated, though.... I must admit, even I have my doubts ;-)

References:

• Ervin RB, Wang CY, Wright JD, Kennedy-Stephenson J. Dietary intake of selected
  minerals for the United States population: 1999-2000. Adv Data. 2004 Apr
  27;(341):1-5. PubMed PMID: 15114720.
• Holick MF. Vitamin D deficiency. N Engl J Med. 2007 Jul 19;357(3):266-81. Review. PubMed PMID: 17634462.
• Portale AA, Halloran BP, Murphy MM, Morris RC Jr. Oral intake of phosphorus can determine the serum concentration of 1,25-dihydroxyvitamin D by determining its production rate in humans. J Clin Invest. 1986 Jan;77(1):7-12. PubMed PMID: 3753709; PubMed Central PMCID: PMC423300.
• Portale AA, Halloran BP, Morris RC Jr. Physiologic regulation of the serum concentration of 1,25-dihydroxyvitamin D by phosphorus in normal men. J Clin Invest. 1989 May;83(5):1494-9. PubMed PMID: 2708521; PubMed Central PMCID: PMC303852.
• Voet, Donald; Voet, Judith G. (2004). Biochemistry. Volume one. Biomolecules, mechanisms of enzyme action, and metabolism, 3rd edition, pp. 663–664. New York: John Wiley & Sons.