Lupus

DHEA: Potential Utility in Lupus

Although conventional HRT with synthetic, equine-derived estrogen may exacerbate SLE as suggested by clinical trial data, there is some evidence that dehydroepiandrosterone (DHEA) supplementation may be helpful in treating people with SLE. People who have lupus are deficient in DHEA, possibly because of inflammation in the adrenal gland, which inhibits DHEA production (Chen CC et al 2004). DHEA has been shown to enhance the production of IL-2 and decrease anti-DNA antibodies in murine models of lupus (van Vollenhoven RF 2000).

In a double-blind, placebo-controlled trial of women with SLE, DHEA resulted in reduction of flare-ups, a reduction in prednisone dose, and decreased disease activity as measured on an SLE disease activity index. The dosage used in the study was 200 mg/day for 3 months. Patients reported a significant overall improvement. In addition, testosterone levels were increased (Chang DM et al 2004). Another study using 200 mg/day of DHEA found that women taking DHEA had fewer lupus flare-ups than did control subjects (Chang DM et al 2004).

DHEA has been proven to protect against the loss of bone density that often accompanies corticosteroid therapy. In another study of women with SLE on corticosteroid therapy, 200 mg/day of DHEA was shown to help maintain bone density (van Vollenhoven RF et al 1999) with minor adverse effects such as acne.

Similarly, people with SLE who have adequate levels of DHEA tend to have higher bone mineral density than those with low serum DHEA levels. Patients receiving corticosteroid therapy had lower DHEA levels in a dose-dependent manner (for example, the more corticosteroid taken, the lower the DHEA level) (Formiga F et al 1997).

Finally, DHEA has been shown to help increase testosterone levels in people with SLE. Numerous studies have shown that those with lupus have decreased testosterone levels. In one study of 25 premenopausal and 25 postmenopausal women, the women taking DHEA showed increased testosterone levels as well as decreased disease activity throughout the entire study (van Vollenhoven RF et al 1998).

Reducing Inflammation Naturally: The Role of Fish Oil

Because inflammation is central to lupus, people with lupus should consider using anti-inflammatories to reduce symptoms. For more general information on inflammation, see the chapter Inflammation. A number of supplements (including fish oil and flaxseed) have been studied specifically in the treatment of people and animals with lupus.

The principal omega-3 polyunsaturated fatty acids are eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA). EPA and DHA are found in fish oil. They can also be derived from alpha-linoleic acid, which is found in flaxseed and walnuts. These fatty acids help build healthy cell membranes and improve membrane stability and have exhibited powerful immunomodulatory and anti-inflammatory properties. A number of studies have examined the role of these fatty acids in people and animals with lupus, with generally positive results.

In a study of people with lupus who had kidney inflammation, highly purified EPA was shown to decrease oxidative stress and alter the ratio of EPA and inflammatory arachidonic acid in favor of EPA (Nakamura S et al 2005). These results have been supported by animal studies showing that EPA and DHA decreased the release of inflammatory chemicals (Fernandes G et al 1996), and that fish oil can delay onset of lupus and other autoimmune disorders and prolong survival (Duffy EM et al 2004; Muthukumar A et al 2004; Simopoulous AP 2002).

Fish oil has synergistic effects with other nutrients. It has been shown to help regulate the activity of antioxidant enzymes in murine models of lupus, making the antioxidants more effective (Bhattacharya A et al 2003). Additionally, when given to mice in a mixture with evening primrose oil, it demonstrated effectiveness in alleviating lupus (Godfrey DG et al 1986).

Fish oil may be helpful in treating kidney disease associated with lupus. In some animal studies, proteinuria was prevented and survival was prolonged (Donadio JV Jr 1991). In a study of people with lupus who had kidney disease, fish oil was found to improve their condition (Clark WF et al 1989).

Flaxseed, in addition to being an alpha-linoleic acid, is a rich source of lignans, which make platelets less sticky, thus helping to reduce clotting and possibly reducing the risk of blood clots (Clark WF et al 1994). Flax lignans help reduce inflammation of the digestive tract and support a healthy balance of intestinal bacteria, as well as assist in the metabolism of hormones.

Finally, retinoic acids, a group of natural and synthetic vitamin A derivatives, have potent anti-inflammatory and immunomodulatory properties. Retinoic acids reduce inflammatory cytokine production. Animals with lupus receiving retinoic acid supplements experienced fewer symptoms, including reduced kidney inflammation and less swelling of the lymph nodes and spleen (Perez de Lema G et al 2004). Immune cell activity was also reduced (Perez de Lema G et al 2004).

Antioxidants

A low level of antioxidants has been shown to be associated with flare-ups. Antioxidants are valuable for their ability to reduce free-radical damage (Parke DV et al 1996). Dietary intake of antioxidants is decreased in people with SLE ( Bae SC et al 2002). Those with lupus exhibit significantly reduced levels of internally produced antioxidants such as glutathione and superoxide dismutase ( Bae SC et al 2002).

Vitamin E. Vitamin E helps stabilize membranes of lysosomes, or immune cells that contain destructive enzymes used to fight intruders. When membranes are unstable, these enzymes cause damage to surrounding healthy tissue. Vitamin E can help prevent the onset of autoimmune attacks by stabilizing membranes of lysosomes (Ayres S Jr et al 1978). The symptoms of mice with lupus that were treated with vitamin E greatly improved. The mice lived longer, immune cell activity was normalized, anti-DNA antibodies were reduced, and kidney function improved (Weimann BJ et al 1999).

Selenium. Selenium is a potent antioxidant that enhances cell repair. Fifty patients with lupus who had low glutathione levels were treated with selenium and vitamin E. The addition of these nutrients increased glutathione levels in 8 weeks (Juhlin L et al 1982). Selenium stimulates vitamin E in its role of immune and antioxidant regulation (Sprietsma JE 1999).

Vitamin D

People with lupus are frequently deficient in vitamin D. There are several reasons for this, including avoidance of the sun because of the photosensitivity that is associated with the disease (Becker A et al 2001; Huisman AM et al 2001). Persons with SLE are at increased risk of low bone mineral density and osteoporosis, partly because of a deficiency in vitamin D but also because of glucocorticoid therapy and disease-associated conditions such as chronic arthritis, reduced physical activity, and endocrine dysfunction (Bultink IE et al 2005; DiMunno O et al 2004).

Because of the risk of osteoporosis and the vitamin D deficiency associated with SLE, vitamin D and calcium supplementation are prescribed initially, especially for postmenopausal women and patients on glucocorticoid therapy (Franchimont N et al 2003; Sen D et al 2001).

In recent years, another interesting role for vitamin D in autoimmune disorders has emerged. Vitamin D has been found to exert profound effects on the immune system, including suppression of T-cell activation (Deluca HF et al 2001; May E et al 2004). Animal studies have shown that vitamin D, along with sufficient calcium intake, can either prevent or markedly suppress autoimmune diseases such as lupus. The mechanism of action may be related to the ability of vitamin D to stimulate IL-4, which suppresses inflammatory T-cell activity. Although studies are still ongoing, this suggests a possible important role for vitamin D in the future treatment of lupus and other immune system disorders (Deluca HF et al 2001).