Cervical Dysplasia

Nutrient Support for a Healthy Cervix

Since as far back as 1981, statistically significant differences in levels of vitamins A and C and beta carotene have been noted between women with cervical dysplasia and healthy controls (Romney SL et al 1981; Wassertheil-Smoller S et al 1981). Other nutrients studied in cervical dysplasia include folate, zinc, and vitamins B6, B12, and E. Changes in diet and nutritional supplementation can reduce the odds of developing cervical cancer (Marshall K 2003; Gagandeep et al 2003; Friedman M et al 2005).

Vitamin A. Vitamin A deficiency has been observed in women with various grades of CIN, and higher levels of vitamin A have been shown to help reduce the risk of progression to cervical cancer (Kwasniewska A et al 1996a; Yeo AS et al 2000; Liu T et al 1993; Shannon J et al 2002; Volz J et al 1995). Vitamin A deficiencies have been linked to CIN among Southwestern American Indian women (Yeo AS et al 2000) and HIV-positive women (French AL et al 2000). Vitamin A also may have a protective effect for black women in the early stages of CIN (Kanetsky PA et al 1998b).

In two studies of women with CIN, a 3-fold to 4.5-fold higher risk of cervical cancer development was seen in those with a low level of vitamin A (Nagata C et al 1999; Wylie-Rosett JA et al 1984). More severe stages of cervical dysplasia were associated with an even lower level of vitamin A (Kwasniewska A et al 1996a). Conversely, high levels of vitamin A were associated with cervical dysplasia regression, particularly in those who were HPV16 positive (Liu T et al 1995).

B vitamins. Numerous studies have also shown vitamin B deficiencies among women with cervical dysplasia.

Vitamin B1. In women with high- and low-grade squamous intraepithelial lesions of the cervix, the level of vitamin B1 was decreased in those with CIN. Progression of cervical dysplasia was associated with reduced levels of vitamin B1 (Hernandez BY 2003)

Vitamin B2. Low levels of vitamin B2 have been associated with an increased risk of low-grade and high-grade CIN (Liu T et al 1993; Hernandez BY et al 2003). Interestingly, vitamin B2 deficiency has been associated with oral contraceptive use.

Vitamin B6. Cervical squamous intraepithelial lesions have been associated with a deficiency of vitamin B6 (Ramaswamy PJ et al 1984).

Vitamin B12. Low levels of vitamin B12 have been associated with both low-grade and high-grade squamous cervical lesions, as well as with HPV persistence (Hernandez BY et al 2003; Sedjo RL et al 2002; Goodman MT et al 2001). However, another study did not show an association between vitamin B12 and women who were either positive or negative for HPV (Sedjo RL et al 2003).

Folic Acid. Insufficient intake of folate is associated with increased risk for cervical dysplasia (Liu T et al 1993; Kwanbunjan K et al 2004; Buckley DI et al 1992; Grio R et al 1993; Kwasniewska A et al 1997; Weinstein SJ et al 2001; Butterworth CE et al 1992; Ziegler RG 1986; Hernandez BY et al 2003; Goodman MT et al 2001). Interestingly, folate deficiency can even be misdiagnosed as cervical dysplasia because their characteristics are similar (Zarcone R et al 1996; Butterworth CE et al 1982).

Other theories to explain the connection between folate deficiency and cervical dysplasia include the increased demand for folate associated with pregnancy and oral contraceptive use (Potischman N et al 1991; Butterworth CE et al 1982). This increased demand results in a folate deficiency in the cervical tissue, which could increase the risk of CIN (Piyathilake CJ et al 2000).

One study suggests that folate deficiency could cause chromosomal damage, such as that seen in cervical cancer, as a result of impaired DNA synthesis or repair (Christensen B 1996). Additional studies state that folate status may be involved in early stages of CIN but not in advanced disease (Potischman N et al 1996; Butterworth CE et al 1992).

Vitamin C. An increased incidence of cervical dysplasia has been found with low levels of vitamin C (ascorbic acid) in several studies (Romney SL et al 1985; Liu T et al 1993; Potischman N et al1996; Palan PR et al 1996; Kwasniewska A et al 1998; Buckley DI et al 1992; de Vet HC et al 1991; Kwasniewska A et al 1996b; Lee GJ et al 2005).

Antioxidants. In general, antioxidant status has been closely linked to cervical dysplasia. Many studies have found low levels of antioxidants in women with various grades of cervical dysplasia. These antioxidants include alpha-tocopherol, gamma-tocopherol, beta-carotene, lutein, lycopene, canthaxanthin, alpha- and beta-cryptoxanthin, coenzyme Q10, and glutathione (Palan PR et al 2003; Palan PR et al 2004; Palan PR et al 1991; Palan PR et al 1996; Giuliano AR et al 1997; Kim SY et al 2003; Ho GY et al 1998; Goodman MT et al 1998). However, the relationship between reduced antioxidant levels and cervical dysplasia is poorly understood. It could be that lower antioxidant levels contribute to development of the condition, or conversely, the disease might cause reduced antioxidant levels as the body seeks to fight the disease. In either case, patients with cervical dysplasia should consider supplementing with a robust antioxidant program.

Minerals. Cervical dysplasia patients have also been found to have abnormal levels of minerals, including copper, selenium, and zinc. Studies have shown that patients with cervical dysplasia and invasive cancers have lower levels of selenium and zinc and a higher level of copper (Kim SY et al 2003; Grail A et al 1986; Rybnikov VI 1985; Liu T et al 1995). Ferritin, an iron-storing protein, has been shown to have a protective effect against cervical dysplasia (Amburgey CF et al 1993).

Cumin. Finally, the spice cumin has been demonstrated in animal studies to reduce the likelihood of developing cervical cancer (Gagandeep et al 2003).

Melatonin

Melatonin may help suppress rapid cell growth and mutation, but this association is still being studied, and some studies have found no effect of melatonin on certain cancer lines (Anisimov VN et al 2000; Panzer A et al 1998). Nevertheless, melatonin is commonly used by patients with cervical dysplasia (Greenlee H et al 2004). One study found that melatonin inhibits the growth of cervical cancer cells in laboratory culture after 48 hours of treatment (Chen LD et al 1995).

Researchers are also looking at variations in melatonin levels among patients with cervical dysplasia. One study revealed lowered melatonin secretion in endometrial cancer patients but not in those with squamous cervical cancer (Karasek M et al 2000).

Working to Fight Off Cervical Cancer

It is fortunate that most cases of cervical dysplasia will not progress to cancer, and if detected, cervical dysplasia is relatively easily treated. If cervical dysplasia progresses to cervical cancer, the treatment options are similar: freezing the cancer or loop electrosurgical excision. If they are treated early enough, it is possible for many women with early-stage cervical cancer to bear children. Advanced cancer that has spread beyond the cervix can require hysterectomy, radiation treatment, or chemotherapy.

While an abnormal Pap smear is reason to carefully adhere to any regimen of follow-up testing and treatment under the care of a physician, studies show certain nutrients also have an ability to fight cervical cancer. Research on cervical cancer has focused on agents that have low toxicity and display activity against HPV-positive cell lines (Vlastos AT et al 2003). The following chemical compounds are under investigation:

Indole-3-carbinol. Indole-3-carbinol, a plant compound from cruciferous vegetables like broccoli and cauliflower, has been studied in connection with the management of CIN. The effectiveness of this plant compound has been documented in small clinical trials (Stanley M 2003b; Bell MC et al 2000). Indole-3-carbinol reduces the formation of 16 alpha-hydroxyestrone, a suspected carcinogen, which in high levels is associated with a greater risk of cervical cancer (Sepkovic DW et al 2001).

Vitamin A. Retinoids, the natural and synthetic forms of vitamin A, inhibit the growth of epithelial cells through transforming growth factor beta (Comerci JT Jr et al 1997). Additionally, retinoids have been reported to support the differentiation of cells (thereby preventing abnormal cervical cancer cells), as well as to affect the immune response of cells (Ahn WS et al 1997; Darwiche N et al 1994).

Coenzyme Q10. Coenzyme Q10 is used by cells for growth and maintenance and as an antioxidant. Some studies have suggested coenzyme Q10 stimulates the immune system. Low levels have been found in certain cancers. Studies suggest the usefulness of coenzyme Q10 in adjuvant therapy in cervical cancer, especially in conjunction with alpha and gamma tocopherols (Palan PR et al 2003).

Green tea. A study of 51 patients showed a reduction of 69 percent of cervical dysplasia lesions in patients who received green tea extracts as either an ointment or capsule (Ahn WS et al 2003).

Melatonin. In animal studies, this hormone is reported to prevent the proliferation of errant cells as well as to help prevent mutation of cells and the breakage of chromosomes (Anisimov VN et al 2000). In lab studies, growth of cervical cancer cells diminished within 48 hours of administration of melatonin (Chen LD et al 1995).

Turmeric (curcumin). Turmeric is effective in regulating cell development, cell division, and programmed cell death (Nagai S et al 2005; Chen A et al 2005; Ramachandran C et al 2005; Sharma RA et al 2005; Seo WG et al 2005; Fang J et al 2005; Weber WM et al 2005; Karunagaran D et al 2005; Furness MS et al 2005; Tilak JC et al 2004; Surh YJ 1999). With regard to cervical cancer, turmeric affects the transcription of the high-risk variant HPV18 as well as other cellular transcription responses (Prusty BK et al 2005). Finally, turmeric combined with the chemotherapeutic agent vinblastine is effective against resistant cervical cancer (Limtrakul P et al 2004; Chearwae W et al 2004).