Phytotherapy and Nutritional Supplements on Breast Cancer 用于乳腺癌治疗的植物疗法和营养补充剂

4.2.6. B Complex Vitamins

B complex vitamins include eight water-soluble vitamins: vitamin B₁ (thiamine), vitamin B₂ (riboflavin), vitamin B₃ (niacin or niacinamide), vitamin B₅ (pantothenic acid), vitamin B₆ (pyridoxine), vitamin B₇(biotin), vitamin B₉ (folic acid), and vitamin B₁₂ (cobalamins; cyanocobalamin) [391]. Each B complex vitamin presents a specific function in the human organs. Some of them can be found naturally in unprocessed food (e.g., beans, meat, poultry, fish, eggs, milk, peas, select fruits, and vegetables) or fortified products (e.g., fortified cereals). Additionally, supplementation with complex B vitamins is also considered as an approach in the case of breast cancer patients or survivors, namely, folic acid [436]. These authors concluded that folic acid supplementation may promote the progression of established breast tumours.

Different conclusions were also reported in the literature related to the effect of B complex vitamins and the risk for breast cancer development [195–199, 201–203, 205–218, 437]. In different clinical studies, despite the fact that several authors verified that some vitamins of B complex (e.g., folate, vitamin B₆, and vitamin B₁₂) did not reduced the risk of developing breast cancer [202, 216, 437] even when stratified by hormone receptor status, other ones reported an association [195, 199, 208–213, 217]. For example, using data from the European Prospective Investigation into Cancer and Nutrition (EPIC), that is, a large prospective cohort study including 23 centres in 10 European countries [203], the plasma folate and vitamin B₁₂ levels were not associated with the risk of breast cancer or by hormone receptor status [437]. Kim and colleagues indicated that high folate plasma concentrations may be associated with increased breast cancer risk among women with a BRCA1/2 mutation (i.e., tumour suppressor genes) [195]. In contrast with these results, a higher dietary folate intake may diminish breast cancer risk and this association may differ by menopausal and sex hormone receptor status [213, 214]. In another based EPIC cohort study, the main conclusions were as follows: high vitamin B₆ plasma concentrations may reduce the breast cancer risk, particularly of estrogen receptor (+) breast cancer; high riboflavin plasma levels may reduce the breast cancer risk in premenopausal but not in postmenopausal women; and homocysteine and the other B vitamins do not seem to influence breast cancer risk [218]. In a large randomized, controlled trials, combined B vitamins daily supplementation (vitamin B₆, 50 mg; vitamin B12, 1 mg; folate, 2.5 mg), administrated over a period of 7.3 years, had no significant effect on the cancer breast risk [196]. In different meta-analysis studies concerning folate plasmatic levels or folate (from diet and/or supplementation), the authors reported no association between folate intake and risk for developing breast cancer [215], and this did not vary by menopausal status or hormonal receptor status [197, 198]. In addition, some of these studies suggested that adequate ingestion of folate may have protective effects against breast cancer risk in women with moderate to high alcohol consumption level [215]. Zhang et al. also achieved similar conclusions; that is, folate intake had little or no effect on the risk of breast cancer; moreover, a dose-response meta-analysis suggested an association between folate intake and breast cancer risk; daily folate intake of 200–320 µg appeared to associate with a lower risk and a daily folate intake >400 µg/d with an increased risk [205]. In a systematic review of clinical studies, Castillo and collaborators suggest a caution in women exposed to high folate intake during the folic acid fortification era, once some studies demonstrated a higher risk of this population for development breast cancer [201]. A weak relationship between the dietary vitamin B2 intake and the reduction of breast cancer risk was also shown in another systematic review and meta-analysis study [207].

Some vitamins of the B complex can interact with one-carbon metabolizing genes which can have an important role in the breast cancer development [219–224]. For example, some case-control studies assessed the association between MTHFR (5,10-methylenetetrahydrofolate reductase) and MTR (methionine synthase) genotypes and breast cancer risk [219–224]. These enzymes are involved in the metabolism of folate and homocysteine and their deficiencies could explain some alterations during breast carcinogenesis. The results proved that some MTHFR (e.g., C667T and 2756GG genotypes) and MTR polymorphisms (e.g., 2756GG genotype) are associated with risk of development breast cancer in different populations [219, 221–224]. Despite the fact that several studies reported an influence of dietary specific B complex vitamins (e.g., folate, vitamin B6, and vitamin B12) intakes on these associations [221–224], some authors stated no association [219, 220, 223, 224]. Dietary methyl group donors such as some B complex vitamins could influence the hypermethylation status of certain genes. Pirouzpanah and colleagues showed that individual B vitamins can present different effects on promoter hypermethylation and methylation-related expression of retinoic acid receptor-beta (RARB) and breast cancer-1 (BRCA1) genes in Iranian patients with breast cancer [225]. Hypermethylation at promoters of RARB and BRCA1 is associated with reduced transcript levels of the respective gene in primary breast cancer tissue samples.

The folate also plays an important role in the regenerating methionine, the methyl donor for methylation, and in the DNA synthesis and repair and, consequently, in carcinogenesis process [438]. In a case-control study involving patients at a tertiary hospital in Uganda, the red blood cell folate levels were not associated with breast cancer risk [204].

Concerning the influence of folate in survival, a prospective cohort study reported that folate supplementation is unlikely to have a significant adverse effect on breast cancer survival among women treated with chemotherapy [200]. In another case-control study, the authors verified that higher dietary vitamins B₁ and B₃intake as well as specific polymorphisms of one-carbon metabolizing genes were associated with improved breast cancer survival [226].

Some chemotherapy often originates cutaneous side effects, namely, dry, itchy, and irritable skin due to nonspecific inhibition of the proliferative activity of keratinocytes. Based on the skin barrier stabilizing effect of vitamin B₃ (niacinamide), Wohlrab et al. [227] conducted a multicentre prospective randomized reference-controlled crossover study and proved the superiority of topical preparation containing niacinamide compared to standard care. The authors demonstrated the cytoprotective and barrier stabilizing effect of vitamin B3 and its prophylactic application for controlling the cutaneous symptoms and maintaining quality of life in breast cancer patients while undergoing cytostatic therapy.