Scientia et Arte

If science were art and art were science, then the howling black wolf has probably swallowed some N-(4-hydroxyphenyl)ethanamide.

Case Study 2: Phytosterolemia (aka Farewell, Vegetables!)

You should eat vegetables

they are healthful.

I shouldn’t eat vegetables

they are harmful.

We (humans) are expected to consider vegetables as a huge part of our diet because they contain plenty of vitamins that function as precursors to the cofactors of the body’s metabolic pathways. Furthermore, they are a perfect source of cellulose and other soluble fibers like pectin, which act as intestinal brooms by regulating the movement of the large intestine and by “sweeping” the intestinal surface of its excrement. Also, fiber keeps the intestinal flora nice and happy, so the body’s natural immunity is regulated, and the production of vitamins K, B2, etc. is controlled. However, a disease may pull us away from our vegetarian journey. Should you eat vegetables, or should you not? Read more and discover for yourself.

Your patient is an 18-year-old boy with atherosclerosis of the coronary arteries. He also has fatty deposits on his tendons and under his skin in various places of his body. Analysis of his blood reveals high concentrations of steroids that cannot be made by mammals, including sitosterol and campesterol, as well as some stigmasterol. Biopsy of the fatty deposits reveals high amounts of sitosterol. One day, he comes in for a blood test and you find relatively high concentrations of 22-dehydrocholesterol, brassicasterol, and 24-methylenecholesterol. It turned out that he had just had a meal of oysters Rockefeller and spaghetti with clam sauce. You now decide to put him on a diet.

Palms of patients with phytosterolemia (before and after treatment). Plant sterols and oils form lumps (xanthomas) and block blood vessels.

Imagine that you are faced with the case above. In general, what kinds of foods should he refrain from eating? Why is it all right for him to eat cheese, eggs, and bacon? Why can he eat shrimp and not mollusks? What other treatment might you recommend?

The patient described above has phytosterolemia, a very rare autosomal recessive disorder that occurs in less than one patient in a million. It causes abnormally high levels of phytosterols (plant sterols) due to the increased absorption of these compounds in the gut and the failure to excrete these into bile. The most common form of phytosterolemia is sitosterolemia because sitosterol concentration is the most pronounced. However, because other plant sterols have elevated levels, phytosterolemia represents the collective term for all the other forms of this disease. Symptoms include:

  • high blood cholesterol
  • tendon xanthomas (sterol deposits in the form of lumps)
  • premature hardening of the arteries
  • xanthomas under the skin
  • arthritis
  • enlarged spleen
  • premature heart disease

Though this disease has not received much attention yet, mutations in either ABCG5 or ABCG8 (ATP binding cassette gene) in chromosome 2 results in sitosterolemia because ABC transporters, specifically sterolin-1 and sterolin-2, cannot be encoded. ABC transporters are important cellular proteins because they make the plasma membrane “leaky”. When a compound enters the cell and the concentration of such compound is above the equilibrium concentration, it is forced to leave the cell via the ABC transporters. However, in the case of sitosterolemia, the necessary ABC transporters are absent, so the passively absorbed plant sterols cannot be actively excreted by the cell. Furthermore, the liver’s capacity to secrete them is also inhibited. Moreover, the synthesis of hydroxymethylglutaryl-coenzyme A reductase (HMG CoA reductase), which controls the biosynthetic pathway of cholesterol, is impaired.

Going back to the questions above, we now know that vegetable oils are not suitable for patients with phytosterolemia for vegetable oils are rich in plant sterols. These sterols are highly concentrated in seeds, kernels, and margarine. Additionally, shellfish contain sterols that are also found in plants and that are contributing factors to the expression of this disease. Hence, mollusks are a big no-no, whereas crustaceans (e.g. shrimps) are allowable as long as they are not eaten in high amounts, which will increase cholesterol levels. Likewise, foods of animal origin are all right provided that they are consumed in moderate amounts.

Since this disease is thought to be brought about by the increased intestinal absorption of plant and molluscan sterols, one possible intervention is to administer cholestyramine, a drug often used for patients with high levels of cholesterol. Cholestyramine is a resin that forms complexes with bile acids (which contains the sterols) in the intestine. It hinders bile acid reabsorption and is excreted in the feces. Thus, the cholesterol balance shifts and more cholesterol is excreted into the bile acid and the liver increases the synthesis of LDL receptors. Because of that, plant sterol absorption is also reduced.

Sources of plant sterols

Now, before you scream and panic about the prospect of not eating vegetables and not being able to fulfill your daily roughage requirement, bear in mind that you should only stay away from vegetable oils, not vegetables per se. I do not advocate the liberal use of pure animal fats because we get enough of them from the meat that we eat anyway. But if the situation calls for oils, then you’ll have to pick animal fat. However, the smoothest road to optimal heart health is still to minimize your fat intake. Eat healthfully, exercise regularly, and keep stress at bay. Your heart will thank you.

References:

http://www.rightdiagnosis.com/s/sitosterolemia/causes.htm

http://www.nejm.org/doi/full/10.1056/NEJMicm000052

http://vitalitymagazine.com/print/plant-sterols-super-nutrients-from-nature/

http://www.lipidsonline.org/slides/slide01.cfm?q=phytosterolemia&dpg=5

http://www.lipidsonline.org/slides/slide01.cfm?q=phytosterolemia&dpg=12

[Post by Ryan Santiago]

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This entry was posted on September 29, 2012 by in Case Studies and tagged .
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