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Regional differences in vitamin D deficiency and disease activity in Italian rheumatoid arthritis patients

Posted on: August 7, 2013   by  [email protected]


A group of Italian researchers recently reported on the serum 25(OH)D levels in patients from 22 rheumatoid arthritis centers distributed across Italy. Much like some of the results I blogged about in Vitamin D levels in children around the world, the results are counter-intuitive.

Rossini M, D’Avola G, Muratore M, et al. Regional differences of vitamin D deficiency in rheumatoid arthritis patients in Italy. Reumatismo. 2013;65(3):113-120.

Vitamin D can be obtained from food and supplements, but in Italy the primary source should be sunlight exposure. Consequently, we would expect the patients in the south of Italy, where the sun is more intense, to have the highest levels. But the researchers found just the opposite.

The figure below presents data from the study. It shows the distribution of serum 25(OH)D by the geographic location of the patient’s clinic – north, central, or south Italy. There is a clear trend – patients in the north of Italy have the highest levels, followed by those in the center. Those who live in south Italy have the lowest levels.


The rheumatoid arthritis centers in northern Italy had an average latitude of 45 degrees and those in south an average latitude of 38 degrees. For those who live in the U.S., these are approximately the latitudes of Portland, Oregon, and San Francisco, two cities Americans consider north of the sun belt and not all that far apart.

Among many other things, the researchers measured how much the patients weighed and how many minutes the patients typically spent in the sun each day. In their discussion of their findings, the researchers say the patients in the south had significantly higher BMIs, which could account for the findings. They also report, “Another explanation is that more hours of sunlight do not mean necessarily longer sun exposure! During summer but also spring, sunlight is so burning that traditionally people living in southern Mediterranean regions avoid sunlight exposure. Indeed, in our patients…sun exposure was significantly shorter in the south as compared to center-north Italy.”

In terms of rheumatoid arthritis the researchers report, “We observed that both disease activity and disability scores were worst in patients living in the southern regions. Of interest are the observed correlations between 25(OH)D serum levels and disease activity and disability scores that remained significant after correction for BMI.”

Scientists continue to find correlations with low vitamin D status and rheumatoid arthritis, but those of us waiting for a definitive study demonstrating a causal effect are still waiting. Meanwhile, we continue to find counter-intuitive results showing that in some studies, at least, individuals living closer to the equator have lower vitamin D levels than those living farther away.

6 Responses to Regional differences in vitamin D deficiency and disease activity in Italian rheumatoid arthritis patients

  1. Anh Phan

    Significant correlation between Vitamin D deficiency and RA disease, the research also showed that people who live in the area having plenty sunshine is not significantly having higher vitamin D serum than people living far away equator.

    Critical thinking: study should consider other factors i.e the subjects’ lifestyle, occupation, food consumption, antioxidant level in blood…We may explain that because the sun so intensive that people afraid to go out to the sun, or cover themselves to avoid sun, less sun exposure then lead to lower vitamin D serum, that might link to RA. However, there might be another explanation: because the sun near equator may contain more radiation waves that inducing free radicals agent on people expose too much on the sun. Free radical cause oxidative stress, that maybe one of the factor contributing to the development of RA and many other diseases. Many study show that free radical agents can be neutralized by antioxidants, which are easily supplied from nutritious food, therefore people have same level of sun exposure may not develop same level of disease. There should be more complicate studies to find out, and the need to be caution not to over simplifying the result of any research.

    Another question: If people consume too less cholesterol, which is a important factor for your body synthesizing vitamin D from the sun, they can have lower vitamin D serum despite having plenty exposure.

  2. Tom Weishaar

    Anh Phan – I think your observation about the impact of sun exposure near the equator, especially on individuals with lighter shades of skin, may have some truth it. However, although we think of Italy as being near Africa and the equator, it turns out that it’s not that close at all. In Asian terms, southern Italy is at about the same latitude as the border between North and South Korea.

    As for cholesterol, your body makes it. Although you’d never know it from the “low cholesterol” labels on food packages, the amount of cholesterol in your diet has almost no correlation with your body’s cholesterol levels.

  3. Rita and Misty

    Here’s an interesting example on cholesterol from my own life experience.

    I suffer from extremely low cholesterol. In my 20s, my cholesterol once tested at 116 total. Seriously now, I can eat a stick of butter daily, and my cholesterol stays low.

    Readers here may remember that for years I had been supplementing with 6,000 iu d3 daily; yet my 25(OH)D level was only 32 ng/ml.

    I have always wondered if my natural tendency towards low cholesterol is a factor in my requiring very large doses of d3 to raise and maintain my 25(OH)D level at optimal levels.

    Be well,

  4. Tom Weishaar

    Rita – there are interesting studies in genetics appearing – that I don’t write yet about because I don’t fully understand them yet – that seem to say there can be small mutations in genes that don’t totally disable the protein the gene makes but that changes the protein’s efficiency. So one small mutation might impact cholesterol production in a way that reduces the type of cholesterol in skin that converts to vitamin D – thus impacting vitamin D levels, too.

    It’s all very complicated and only just beginning to be understood. However, the important point is that one of the 48 “nuclear receptors” in humans that control which genes are making proteins and which aren’t is turned on and off by the activated form of vitamin D. This nuclear receptor, known as VDR, is found in cells throughout the body and appears to control production of about 3% of the proteins your body can make.


  5. Rita and Misty

    Thanks, Tom, for your reply. It is all very fascinating stuff, for sure.

  6. DrMargaretTaylor

    Another possibility is low boron. This is from an excellent article called ‘Nothing boring about boron’ by Lara Pizzorno – full text is available via PubMed. The numbers refer to references in the paper.
    Prevention of Vitamin-D Deficiency
    Boron has been shown to increase serum levels of
    25-hydroxyvitamin D3 (25[OH]D3) in animal studies4,24 and of vitamin D–deficient individuals in human studies.25,26 In a clinical trial25 in which middle-aged men and women (n = 15) were placed on a low-boron diet, which was also marginal in magnesium and copper status, for 63 days (0.23 mg B/2000 kcal), 25(OH)D3 rose significantly after boron supplementation (3 mg/d as sodium borate) for an additional 49 days. Levels of 25(OH)D3 rose from an average of 44.9 nM after the 63 days of boron deprivation to 62.4 nM after the 49 days of boron repletion, a 39% increase.
    Similar results were seen in an open pilot study of
    middle-aged individuals (n = 13) predetermined to be
    vitamin D deficient (serum 25[OH]D3 < 12 ng/mL). Levels
    of 25(OH)D3 were studied during boron supplementation
    of 6 mg/d for 60 days using calcium fructoborate,
    Ca([C6H10O6]2B)2∙4H2O, a boron-containing complex that occurs naturally in fruit.26 The study took place in Serbia with supplementation beginning in October and concluding by January; in other words, the study occurred during the fall transition to winter, a time when vitamin-D status would be expected to worsen. Yet, with boron supplementation, 25(OH)D3 levels rose significantly, with an average rise of 20%.

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