About a year ago, one of my paleo-dieting, vitamin D-supplementing patients developed a salivary stone (sialolith), diagnosed by an oral surgeon. A salivary stone consists of calcium phosphate blocking the salivary duct and saliva flow, resulting in swelling of the gland during meals when saliva production increases.
The patient refused the surgical treatment for this condition and consulted me for non-surgical treatment. I began treating her with acupuncture and a Chinese herbal formula clinically proven effective for this condition. Over the course of about 10 months of treatment consisting primarily of drinking an herbal tea every day, the stone dissolved, confirmed by the surgeon who diagnosed it.
In the meantime (several months into the treatment), she had her semi-annual vitamin D test which found a serum 25-hydroxyvitamin D level of 82ng/mL. This came after six months of supplementing with 4000-5000 IU daily. When I saw this level I knew it fell in the range suggested as possibly optimum by Cannell at the Vitamin D Council (50-80ng/mL), but I advised her to reduce her vitamin D intake by half (from ~4000-5000 IU per day) and let it decline to 30- 50ng/mL.
Over the course of the next 7-8 months the patient had progressively less swelling during meals, and I could see the stone shrinking. However, it shrank so much more slowly than I expected that I started to wonder if a high intake or elevated blood level of vitamin D counteracted the effect of the herbs, and contributed to the formation of this stone. So I did a PubMed search to find out if anyone had ever investigated the relationship between vitamin D levels and formation of sialoliths.
I found one study that looked for increased salivary stone formation in women taking vitamin D, calcium, and alendronate (PhosomaxÔ). This study found no evidence of increased sialolithiasis in this group of women. However, the abstract does not state the dose of vitamin D used, and I don’t want to pay to view the full text. I feel pretty confident that this trial did not use a vitamin D dose greater than 2000 IU daily, whereas previous to her stone formation my patient was taking 4000-5000 IU.
Then I found the abstract of an experimental study by Westhofen et al: Calcium redistribution, calcification and stone formation in the parotid gland during experimental stimulation and hypercalcaemia. In this study Westhofen et al induced hypercalcemia in rats by administration of dihydrotachysterol, a synthetic vitamin D analogue. They reported:
“During hypercalcaemia (induced by dihydrotachysterol), a calcium overloading of the cell membrane and intracellular buffer organelles without calcification was observed. Combined stimulation and hypercalcaemia induced an excessive calcium overloading of all intra-and extracellular calcium depots with excessive calcium release into the acinar lumina resulting in calcium phosphate aggregates and stone formation. Secretory stimulation and simultaneous hypercalcaemia exert potentiating effects on intracellular and intraluminal calcification proposing an importance for pathogenesis of human sialolithiasis.” [Emphasis added.]
Since vitamin D increases blood calcium by increasing both intestinal absorption and bone resorption, this suggested to me that excessive vitamin D could indeed increase the risk of forming salivary stones, particularly in people like my patient who form large deposits of calculus (thus have a tendency to high salivary calcium phosphate).
By the time I figured all this out, my patient’s stone had dissolved, confirmed by the same oral surgeon who diagnosed it. By consuming vitamin D only intermittently, her vitamin D level fell to 39 ng/ML during the treatment period.
Then, in the process of working on my series on acid-base balance, I found that Eskimos probably had suboptimal intakes of magnesium. I got a hold of a couple of studies looking at the effect of magnesium deficiency on bone health
Surveys since 1985 indicate that the typical U.S. individual does not ingest magnesium at amounts recommended by the RDA (1, 2) of 400mg for adult men and 310mg for adult women. U.S. adults commonly consume 50% or less than recommended levels.
Rude et al showed that restricting animals to magnesium intakes equivalent to just half of the adult human RDA resulted in “bone loss, decrease in osteoblasts, and an increase in osteoclasts by histomorphometry” (3). Six months of low magnesium intake reduced trabecular bone volume significantly.
They also found that low magnesium intake reduced levels of activated vitamin D, i.e. 1,25 dihydroxyvitamin D, aka calcitriol, by 50%! This suggests that magnesium deficiency profoundly impairs activation of vitamin D. This would mean that people who do not get adequate magnesium would show signs of vitamin D deficiency despite adequate sun exposure or vitamin D intake. Conversely, people who consume more magnesium-rich foods, such as my paleo-dieting patient, require less vitamin D, and may more easily suffer from vitamin D excess.
Finally, Rude et al also found that magnesium deficiency increased markers of bone inflammation (cytokines) and RANKL, also favoring bone resorption.
I exchanged a few emails with Dr. Stephan Guyenet (Whole Health Source) discussing this and he graciously shared a few other studies of interest here.
First, Batchelor and Compston studied the effects of cereal fiber on vitamin D pharmacokinetics in humans, following up on a study by Ford et al which “demonstrated biochemical improvement in ten patients with rickets or osteomalacia following the substitution of white leavened bread for chappattis in the diet” (4). They gave healthy volunteers bran supplying 20g of cereal fiber daily. They demonstrated that the high intake of cereal fiber reduced the plasma half-life of 25-hydroxyvitamin D from 27.5 days to 19.2 days. Since vitamin D appears in bile and cereal fibers may bind bile, Batchelor and Compston suggested that this may explain the loss of vitamin D in the cereal-fiber-supplemented individuals.
This suggests conversely that people not consuming cereal fiber have a superior retention of vitamin D and would not require the same high doses as people consuming cereal-based diets. Again, people on paleo diets would then have a greater susceptibility to adverse effects of high dose vitamin D.
Another study by Zanchi et al looked at bone metabolism in children suffering from celiac disease compared to controls (5). Among the untreated celiacs, 40% had low blood calcium, 11% low blood magnesium, more than 50% had hyperparathyroidism, and 35% had blood 25(OH)vitamin D below 20ng/mL (frank deficiency). The untreated celiacs had an average 25(OH)vitamin D less than half of healthy control subjects. Ten of 20 patients who had at least two positive laboratory tests had osteopenia, which resolved after 6 months on a gluten-free diet. Unfortunately, adults with late-diagnosed celiac do not have the same pattern of recovery of bone mineral density on gluten-free diets.
This shows that ingestion of gluten can reduce vitamin D levels in celiac patients. Since at least two studies (6, 7) have shown that gliadin increases intestinal permeability of non-celiacs as well as celiacs, I suspect that gluten may affect vitamin D status in non-celiacs. If so, a gluten-free paleo diet may increase the effectiveness of vitamin D, reducing the required dose and making paleo dieters more susceptible to vitamin D overdose.
By the way, Jorde et al gave 324 overweight or obese subjects either 40K IU or 20K IU weekly (5714 or 2857 IU daily) of vitamin D for a year. They found no reduction in levels of markers of inflammation over that time, compared to unsupplemented subjects.
It could very well turn out that elevated vitamin D levels don’t themselves confer all the benefits linked to vitamin D status. Higher vitamin D levels linked with lower risks of some chronic diseases (e.g. skeletal and autoimmune in particular) may turn out to only serve as a marker for the beneficial effects of outdoor activity, better micronutrient status (e.g. magnesium above), or lower intake of or susceptibility to the effects of gluten.
Urashima et al reported this month that school children given 1200 IU of vitamin D daily had nearly half the incidence of influenza and one-sixth the incidence of asthma found in unsupplemented children. Thus, it appears that improved vitamin D status does improve innate immunity against infectious disease and reduce susceptibility to asthma.
For now I recommend keeping your serum vitamin D level between 40 and 60 ng/ml (edited 3/26/10) and not making an effort to obtain the higher levels (50-80ng/mL) recommended by the Vitamin D Council. I still recommend using 10K IU for 1-3 days at the onset of symptoms of a cold or flu, to enhance the innate immune response and terminate the infection.
In short, it seems likely that paleo dieters probably require less vitamin D supplementation than people on grain-based diets, and might have a higher risk of side effects from chronic high dose supplementation.
1. Earl S. Ford and Ali H. Mokdad. Dietary Magnesium Intake in a National Sample of U.S. Adults. J. Nutr. 133:2879-2882, September 2003
2. K. J. Morgan, G. L. Stampley, M. E. Zabik and D. R. Fischer. Magnesium and calcium dietary intakes of the U.S. population. Journal of the American College of Nutrition, Vol 4, Issue 2 195-206
3. Robert K. Rude, MD, Frederick R. Singer, MD and Helen E. Gruber, PhD. Skeletal and Hormonal Effects of Magnesium Deficiency. Journal of the American College of Nutrition, Vol. 28, No. 2, 131-141 (2009)
4. Batchelor and Compston. Reduced plasma half-life of radio-labelled 25-hydroxyvitamin D, in
subjects receiving a high-fibre diet. Br. J. Nutr. (1983). 49, 213.
5. Zanchi et al. Bone Metabolism in Celiac Disease. J Pediatr 2008;153:262-5.
6. Drago et al. Gliadin, zonulin and gut permeability: Effects on celiac and non-celiac
intestinal mucosa and intestinal cell lines. Scandinavian Journal of Gastroenterology, 2006; 41: 408-419.
7. Bernardo et al. Is gliadin really safe for non-coeliac individuals? Production of interleukin 15 in biopsy culture from non-coeliac individuals challenged with gliadin peptides. Gut 2007;56;889-890.
8. Jorde et al. No effect of supplementation with cholecalciferol on cytokines and markers of inflammation in overweight and obese subjects.
9. Urashima et al. Randomized trial of vitamin D supplementation to prevent seasonal influenza A in schoolchildren. Am J Clin Nutr (March 10, 2010).
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