Aug. 15, 2012

Lupus-Related Changes in Energy Metabolism

Metabolic disturbances associated with systemic lupus erythematosus
Wu T, Xie C, Han J, Ye Y, Weiel J, Li Q, Blanco I, Ahn C, Olsen N, Putterman C, Saxena R, and Mohan C. (2012). PLoS One 7: e37210. [Epub ahead of print]

What is the topic?

Research on possible metabolic changes in people with lupus is relatively scarce. Yet, information about how energy-generating processes are affected in them could be very useful from the diagnostic and therapeutic viewpoints.

What did the researchers hope to learn?

The researchers hoped to learn about possible changes in a number of bodily substances crucial for metabolic pathways in people with lupus, and to compare them to that of healthy individuals and people with rheumatoid arthritis.

Who was studied?

For the primary metabolic study, 20 lupus patients were recruited from the Renal Clinic at the University of Texas Southwestern Medical Center in Dallas (10 of whom had active kidney disease). For purposes of comparison, 9 healthy people were recruited to the study from the Dallas Autoimmune Disease Registry.

For the validation study, 38 lupus patients and 20 rheumatoid arthritis patients were recruited to the study from the Albert Einstein College of Medicine Rheumatology Clinic in the Bronx, New York.

How was the study conducted?

Lupus disease activity was measured in each lupus patient with the Systemic Lupus Erythematosus Disease Activity Index (SLEDAI). A metabolic profile was obtained for each study participant by measurement of multiple metabolic markers with appropriate laboratory techniques.

What did the researchers find?

Patients in the primary metabolic study were mostly African-American or Hispanic women, about 34 years of age, with a body mass index (BMI) of 29, which did not differ significantly from that of the healthy participants. About half of the lupus patients had kidney involvement or had anti-double-stranded DNA antibodies, and most of them had moderate disease activity (SLEDAI = 5). Many of these lupus patients also had high blood pressure and were taking angiotensin-converting enzyme (ACE) inhibitors; in addition, they were taking hydroxychloroquine, or mycophenolate mofetil, and most of them were taking prednisone. Patients in the validation study included mostly African-American or Hispanic lupus patients that were, as a group, matched with rheumatoid arthritis patients by age, gender, and ethnicity. Some of the lupus patients had other diseases, including deep vein thrombosis, diabetes, cardiovascular disease, and/or other diseases.

Many metabolic markers that are participants in key metabolic pathways were found to be significantly reduced in lupus patients, as compared to the healthy people or rheumatoid arthritis patients. These markers were all identified as being involved in energy metabolism, including those involved in extraction of energy from carbohydrates, lipids, and amino acids.

There was also evidence of significantly increased (oxidative) damage to lipids, indicating increased “oxidative stress” (damage to lipid molecules as a side effect of normal metabolic processes), as well as decreased antioxidant activity, such as decreases in vitamin B6 and vitamin E, in the lupus patients.

Some, but not all, of the changes found in the metabolic markers showed significant association with specific drugs being taken, such as prednisone and acetaminophen. However, no significant associations were observed with hydroxychloroquine or mycophenolate mofetil, even when their dosages were taken into account.

None of the metabolic markers examined, however, was associated with lupus disease activity, disease duration, levels of anti-double-stranded DNA, or kidney damage.

What were the limitations of the study?

The causes and functional significance of the metabolic changes described in this study remain unknown. Also, whether these metabolic changes are a cause or consequence of lupus is unknown. In addition, it will be important for future studies to assess metabolic changes in larger groups of lupus patients from other ethnic groups and with more diverse disease manifestations.

What do the results mean for you?

This research indicates a profound degree of shutdown of all energy-generating metabolic pathways, including those of carbohydrates, lipids, and amino acids. The implication of these findings is that lupus patients have a significant reduction in the production of energy-rich molecules, which may help to explain the chronic fatigue that lupus patients oftentimes experience. Further research is needed, however, to definitively conclude this.

The authors also suggest that their findings have implications for possible dietary manipulations that may benefit people with lupus, including supplementation with fish oil, vitamins (particularly vitamin B), and choline. People with lupus should consult their physicians before making any significant changes in their dietary regimens, including, but not limited to, the use of dietary supplements.


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