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Thursday, August 4, 2011

Absorbing calcium

Although the cause of hypercalcemia is a mystery 1in Williams syndrome, we do know a little about how the calcium is absorbed in the gut. Many people think that the stomach is the main area of digestion in your body. Although it does digest proteins, the majority of the food is broken down and absorbed by the small intestine. The lining inside of your small intestine is a network of finger-like bumps that are filled with blood vessels and covered by a very thin layer of skin that sits between the vessels and the food/enzyme mixture in your gut.




Most calcium in your small intestine is absorbed in the lower regions called the ileum and jejunum. These are the main portions of your intestine that absorb nutrients and minerals. Calcium here will move passively into the blood stream. This means that it can easily slip through little spaces in the skin layer (called the epithelium) and into the blood. If your diet provides your body with enough calcium, this is the main type of transport you'll use.




If calcium levels are low, your body has to work a little harder to get the amount it needs. This is where vitamin D comes in. Vitamin D operates channels that collect calcium in the upper third of the small intestine, called the duodenum. These channels are activated when vitamin D binds to proteins in the epithelium (skin) layer. These proteins work with active transport, where the body uses energy to pump the calcium into the blood stream, increasing its levels in the blood. This is why, if you increase the vitamin D in your diet, you end up increasing the calcium in your blood stream.




This vitamin D metabolism is one of three theories I could find that try to explain infantile hypercalcemia in WS. Researchers have found that when children with hypercalcemia are managing their calcium levels and only slightly rise the vitamin D in their diet, their calcium levels increase dramatically. They found that by only making small increases in vitamin D, children with WS absorb 2-3 times more calcium than what would be expected in a typical child.




Another factor that influences calcium absorption is the type of food you eat. If you are a milk drinker, you're going to have more passive calcium absorption- the easy kind in the lower intestine. Milk contains sugars called lactose and an enzyme called lactase both of which help the body collect the calcium and absorb it into the blood stream. Other foods also contain calcium, such as spinach. Foods that are high in fiber and contain calcium tend to be harder for your body to digest. The fiber, called oxalate, binds to the calcium and holds on to it as it passes through the gut. Therefore, if your primary calcium sources are in high fiber foods, you will essentially absorb less of them and excrete more due to the food's chemical nature.







Oxalate has other affects on your body, too. If the level of calcium is low, your body will start to absorb more oxalate instead of excreting it. Essentially, if you are in a pinch for calcium, you'll take what you can get even if it's in a form that you don't really prefer. The increase in oxalate signals the kidneys to work harder to get rid of it. Calcium oxalate then builds up in the kidneys and can cause stones, or nephrocalcinosis (see the growth and diet page on this blog). This is why some doctors will place a child with hypercalcemia on a low oxalate diet- to prevent the uptake of calcium and reduce dangers of developing kidney stones.



It's important to note that although many WS infants with hypercalcemia have higher than normal levels of vitamin D, there are exceptions to the rule. There is a significant population of individuals who have high levels of calcium and LOW levels of vitamin D. Since most foods contain both, this can create quite the dilemma to try and maintain proper levels of each. Stay tuned for future blog posts discussing this topic and other theories of why our little ones have hypercalcemia!

















4 comments:

  1. You've described how vitamin D is metabolised, and how this raises calcium levels in the blood when calcium is too low. There is an additional component of this process, which is how the body reacts when the calcium is too high. When calcium is too high, the response is to break down and eliminate vitamin D.

    There are two primary mechanisms by which vitamin D is excreted. The first is via the kidneys, and this occurs in response to high calcium. When there is too much calcium in the blood, the kidneys produce an enzyme called 24-hydroxylase (CYP24A1) which modifies the vitamin D so that it is water-soluble. This is then excreted in the urine.

    In short, the body's response to high calcium is low vitamin D.

    The second mechanism of vitamin D elimination is via the liver. When there is too much vitamin D, the liver produces an enzyme called CYP3A4. This breaks down the vitamin D, which is then excreted via the bile duct. This does not necessarily occur in response to high calcium, as the liver will remove excess vitamin D even if calcium levels are normal.

    CYP3A4 is a general-purpose garbage collector, and is responsible for disposing of a number of substances besides vitamin D, including many prescription drugs. Some of the adverse effects of vitamin D overdose are attributable not to vitamin D itself but to increased CYP3A4, and some prescription drugs carry a warning that taking vitamin D may reduce the effectiveness of the drug. The cholesterol-lowering drug atorvastatin is one of the most-studied examples, but a large number of drugs are potentially affected by vitamin D.

    This brings us to the question of why babies get hypercalcemia in response to vitamin D. It turns out that this is not limited to Williams syndrome, and all babies are somewhat susceptible to developing hypercalcemia. The reason is that infants' livers do not produce much CYP3A4. As the child gets older, the liver produces more of this enzyme and gets better at removing excess vitamin D. Why people with Williams syndrome are particularly susceptible to vitamin D problems remains unclear, but this mechanism of vitamin D removal is the same as in people who do not have Williams syndrome.

    Anyway, I hope this answers your question as to why HIGH calcium, results in LOW vitamin D, and why children with with Williams syndrome do not truly "outgrow" their vitamin D problems, just that their livers get better at disposing of it.

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  2. Thank you for sharing Pixi Stix! This answers one of our big questions. Your explanation makes perfect sense. :)

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  3. Pixi & Sarah, In laymans terms, Is there a recommended amount of calcium & Vitamin D u would give your WS child (3yrs. old) on a daily basis?

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  4. Honestly, Marie, I wouldn't want to give you a recommendation on that because I'm not a medical professional. You'd want to talk to your child's pediatrician or dietician if they have one and ask. My daughter hasn't had any issues with vitamin D and calcium so I just follow nutrition guidelines and make sure she gets 100% BUT in general they say not to give vitamins that contain vitamin D or calcium unless directed by your doctor due to these issues. Again, it's hard to say because every kid is different...

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