B-vitamins intake. B-vitamins may reduce the risk of cardiovascular disease by ways of reducing homocysteine levels. A meta-analysis of randomized clinical trial showed clear evidence that folate and vitamin B-12 supplementation reduce blood levels of homocysteine (Homocysteine Lowering Trialists’ Collaboration, 2005). Observational studies also show a reduction in the risk of cardiovascular disease in individuals with high folate and B6 intake (Rimm et al, 1998; Bazzano et al, 2006). Recent randomized trials show little benefit of folate or B-12 on risks of cardiovascular disease (Bazzano et al, 2006). However, these recent trials have been performed primarily in patients with existing cardiovascular disease, of relatively short duration, and some were in populations where the food supply was fortified with folate. A meta-analysis published in Lancet 2 years ago showed a clear benefit of folic acid supplementation in reducing the risk of stroke, especially in populations with lower folate intake (Wang et al, 2007). In addition to the effects on cardiovascular health, folic acid supplementation reduces the risk of neural tube defects and other congenital anomalies (Goh et al, 2006).
Calcium and vitamin D intake. Calcium and vitamin D intakes are essential for maintaining bone mass. A meta-analysis of 33 clinical studies showed a positive effect of 1000 mg of calcium supplementation on bone mass in young and premenopausal women (Welten et al, 1995), while another meta-analysis showed that dairy products were only beneficial in young white women (Weinsier and Krumdieck, 2000). Around menopause, when bone resorption is greater than formation, calcium supplementation does not prevent bone loss (Dawson-Hughes et al, 1990). However, after about 5 years postmenopause, calcium supplementation prevents further bone loss and may increase bone mass by 1.6–2% (Shea et al, 2004). More recently, a large, randomized-control clinical trial in 36 282 healthy postmenopausal women, the Women’s Health Initiative (WHI) study, indicated that prolonged calcium and vitamin D supplementation significantly reduced bone loss at the hip (Jackson et al, 2006). Despite these apparent benefits of calcium intake on bone mineral density, these studies can be misleading because the effects are small and temporary; once calcium supplementation is stopped, bone mineral density typically returns to that of the placebo group.
Calcium and vitamin D supplementation may prevent fracture risk. A meta-analysis of 15 clinical trials with calcium supplementation observed a 23% reduction in vertebral fractures and 14% in non-vertebral fractures (Shea et al, 2004). Two meta-analyses of calcium and vitamin D supplementation trials in 45 000 to 64 000 individuals 50 years and older found a 25% reduction in hip fracture risk (Tang et al, 2007), a 12% reduction of all fractures and 24% reduction of all fractures in those with high compliance to the treatment (Boonen et al, 2007). The WHI trial found a significant 29% decrease in the risk of hip fracture with 1000 mg day−1 of calcium and 400 IU day−1 of vitamin D supplementation among participants with good compliance to the treatment (Jackson et al, 2006). One of the difficulties in evaluating the effects of calcium on fracture risk is that in many studies it has been combined with vitamin D. In a meta-analysis of intervention trials using vitamin D supplementation, doses less than 700 IU day−1 had no effect on risk of fractures, but higher doses of 700–800 IU day−1 significantly reduced the risk of hip fractures by 26%, and reduced non-vertebral fractures by 23% (Bischoff-Ferrari et al, 2005). However, a recent meta-analysis found no relation between calcium intake and risk of hip fractures in prospective cohort studies, and no significant reduction in the risk of non-vertebral fractures in randomized trial of calcium supplements that did not include vitamin D, with a possible increase in risk (Bischoff-Ferrari et al, 2007). Thus, most people appear to be consuming sufficient calcium for bone health, and increases in vitamin D are likely to reduce risk of fractures, either by effects on bone health or reductions of falls.
Calcium intake has been hypothesized to reduce the risk of cardiovascular conditions, possibly by decreases in blood pressure. In the Nurses’ Health Study, low calcium intake was associated with greater risk of ischemic stroke in middle-aged American women (Iso et al, 1999); intake above 600 mg day−1 did not appear to further reduce the risk. In the same population, calcium intake was not related to the risk of CHD (Al-Delaimy et al, 2003). Several meta-analyses of clinical trials suggest that calcium supplementation may reduce the risk for high blood pressure (Allender et al, 1996; Griffith et al, 1999; Hajjar et al, 2003; Dickinson et al, 2006; van Mierlo et al, 2006), but the effect appears to be small and may only benefit those with low dietary intakes. Although the evidence has been inconsistent, in some circumstances, higher calcium intake may reduce the risk of pre-eclampsia (Hofmeyr et al, 2006).
Vitamin D may also be related to systemic and local inflammation. A meta-analysis of 19 cross-sectional, 13 case–control and 12 prospective studies suggests that low serum 25-hydroxyvitamin D [25(OH)D] levels or vitamin D intake is associated with glucose intolerance, β cell function and insulin resistance, and with the risk of diabetes and metabolic syndrome in individuals from different populations and age groups (Pittas et al, 2007). The Nurses’ Health Study also found that a high intake of calcium and vitamin D was associated with a reduce risk of type 2 diabetes compared with a low intake (Pittas et al, 2006). Furthermore, vitamin D and calcium deficiencies result in bone loss and increased inflammation, which are both components of periodontal disease (Hildebolt, 2005). Vitamin D also has immune-modulatory functions by which it may reduce periodontitis susceptibility (Dietrich et al, 2005). Serum levels of 25(OH)D have been associated with gingivitis (Dietrich et al, 2005) and periodontal disease (Dietrich et al, 2004). Low dietary calcium and dairy products intake are associated with increased levels of periodontal disease (Nishida et al, 2000a; Al-Zahrani, 2006). A clinical trial of calcium and vitamin D supplementation showed increased tooth retention after 3 years in the elderly people (Krall et al, 2001).
Few studies have assessed the protective effects of foods on caries. Recent studies have suggested that milk and cheese are related to reduced risk of caries; however, this is still not well established. Postulated mechanisms may involve buffering of acids, salivary stimulation, reduction of bacterial adhesion, reduction of enamel demineralization, and/or promotion of remineralization by casein and ionizable calcium and phosphorous (Moynihan et al, 1999; Kashket and DePaola, 2002).
Calcium and vitamin D intake may also be related to lower colon cancer risk. In a pooled analysis of 10 cohort studies, with more than 500 000 subjects followed for up to 16 years, those with the highest intake of milk and calcium had significantly reduced risk of colon cancer (Cho et al, 2004). This effect was stronger for calcium from foods compared with calcium from supplements (Hartman et al, 2005). Evidence from large cohort trials (the Cancer Prevention Study II Nutrition Cohort and the Multiethnic Cohort Study) also favors a protective effect among men (McCullough et al, 2003; Park et al, 2007) but not among women (Lin et al, 2005; Wactawski-Wende et al, 2006). Meta-analyses of clinical trials also indicate that calcium supplementation may prevent colorectal adenomatous polyps (Weingarten et al, 2004) and recurrent colorectal adenomas (Shaukat et al, 2005). In addition, higher blood levels of vitamin D (25-OH D) have been consistently associated with reduced risk of colorectal cancer and higher intakes of vitamin D have also been related to lower risk (Gorham et al, 2005; Wei et al, 2008). Some evidences suggest that higher vitamin D levels may reduce the risk of breast cancer (Autier and Gandini, 2007; Garland et al, 2007; Gissel et al, 2008) and decrease total mortality rates (Autier and Gandini, 2007).
On the other hand, calcium and dairy product intake may be related to higher risk of prostate cancer. Meta-analyses of prospective studies indicate that high consumption of milk and dairy products (about >3 servings per day) increases the risk of prostate cancer (Gao et al, 2005; Qin et al, 2007; WCRF, 2007). A large prospective study found >2.75 servings per day of dairy products, particularly low-fat types and >2000 mg day−1 of calcium were modestly associated with increased risks only for non-aggressive prostate cancer (Ahn et al, 2007), but in most studies the associations have been primarily with metastatic or fatal prostate cancer. Although consumption of dairy products has been associated with the risk of ovarian cancer in some studies, in a large pooled analysis, the association with total dairy products and calcium intake was not significantly associated with the risk of this cancer (Genkinger et al, 2006). However, when expressed as lactose intake, a modest increase in risk was seen at levels equivalent to about three glasses of milk per day. Milk or dairy product consumption has not been associated with increased risk of breast cancer (Missmer et al, 2002; Shin et al, 2002; McCullough et al, 2005).