Emerging Health Benefits for TRADITIONAL NUTRIENTS
Dietary vitamins and minerals have been studied for decades, initially for the treatment of deficiency diseases related to their essentiality, but later, for their impact on chronic conditions. They have been most recently recognized for their beneficial roles in such areas as weight loss, age-related macular degeneration and even fertility. Here, the focus is on new findings for vitamins A, C, D and E, and minerals, including calcium, selenium and zinc, as well as more recent entries into the field of nutritional sciences--pre- and probiotics, and omega fatty acids.
Antioxidants protect cells from the damaging effects of free radicals, which are molecules that contain an unshared electron and react rapidly with oxygen to form reactive oxygen species (ROS)1. Many of the protective effects of certain vitamins, as well as minerals, such as zinc and selenium, can be attributed to their ability to act as antioxidants, or in conjunction with antioxidants, and protect cells from the damaging effects of ROS.
Of interest, omega-3 fatty acids have recently been reported to reduce oxidative stress in 59 overweight men with high cholesterol levels who received daily either 4g of eicosapentaenoic acid (EPA), docosahexaenoic acid (DHA) or olive oil (placebo) for six weeks. EPA and DHA both reduced urine levels of F2-isoprostanes (a marker of oxidative stress) by 24 and 14%, respectively2.
Although the role of vitamins and minerals in cancer prevention has long been debated, new research suggests protective effects against cancer formation, through reducing the damaging effects of free radicals. For example, case-controlled studies have found an inverse association between dietary vitamin C intake and cancers of the lung, breast, colon or rectum, stomach, oral cavity, larynx or pharynx, and esophagus. Plasma concentrations of the vitamin are generally lower in people with cancer than controls3.
In a subset of 82,234 women aged 33ñ60 years, from the "Nurses' Health Study," consumption of an average of 205mg/day of vitamin C from food (highest quintile) compared with an average of 70mg/day (lowest quintile) was associated with a 63% lower risk of breast cancer4.
Supplementation with vitamins C, as well as A, E and folate, has been linked to a 24-30% lower colon cancer risk, as determined from an analysis of primary data from 13 cohort studies with over 650,000 participants5.
Vitamin D plays a role in the prevention of colon, prostate and breast cancers. In a prospective, cross-sectional study of 3,121 adults, aged =50 years, who underwent a colonoscopy, those with the highest vitamin D intakes (>645IU/day) had a significantly lower risk of cancerous lesions6.
A clinical trial focused on bone health in 1,179 postmenopausal women found subjects who supplemented daily with calcium (1,400-1,500mg) and vitamin D3 (1,100IU) had a significantly lower incidence of cancer, over four years, compared to women taking a placebo7. New research also includes positive effects of vitamin D on obesity-induced endometrial lesions in mice, prompting the investigators to note that women con¨cerned about their risk should consume vitamin D supplements or spend a few more minutes each week in the sun8.
Observational studies indicate death from lung, colorectal and prostate cancers is lower among people with higher blood levels or intake of selenium9. In a multi-center study focusing on skin cancer, 200µg of selenium did not affect recurrence of skin lesions, but significantly reduced the occurrence and death from total cancers. 10 As an antioxidant, selenium can help protect the body from damaging effects of free radicals and may also prevent or slow tumor growth, by enhancing immune cell activity and suppressing development of blood vessels to the tumor.
A scientific investigation focused on EPA and DHA from fish oil supplements revealed regular consumption for at least 10 years reduced the risk of breast cancer by 32%. The extensive trial involved 35,016 postmenopausal women, between the ages of 50-76, who completed a questionnaire about their use of supplements 11.
Age-related Macular Degeneration (AMD)
The cumulative effects of oxidative stress in retinal damage have been postulated to play a role in the development of AMD. Prospective cohort studies have shown people with relatively high dietary intakes of vitamin E (about 30IU/day) have approximately 20% lower risk of developing AMD than people with low intakes (<15IU/day) 12.
Participants with early-stage AMD reduced the progression of their disease by taking a daily supplement of vitamin E (400IU dl-alpha-tocopheryl acetate), vitamin C (500mg), beta-carotene (15mg), zinc (80mg) and copper (2mg) for an average of 6.3 years compared to a placebo 13.
A population-based cohort study demonstrated adults aged 55 years or older who had high dietary intakes of vitamin C, as well as beta-carotene, zinc and vitamin E, also showed a reduced risk of AMD 14.
Omega-3 fatty acids appear to protect against AMD. In a study of 2,520 adults aged 65-84 who completed a food-frequency questionnaire, those with advanced AMD were found to consume significantly less fish or shellfish than age-matched cohorts 15.
Plaque build-up associated with oxidative stress can increase brain cell damage and death, as people age. Individuals consuming the highest levels of vitamin E showed a 25% less likelihood of developing dementia than when intakes were lower; benefits were attributed to its antioxidant activity 16. These observations were noted in a 10-year follow-up study of 5,395 people aged 55 and older with an average intake of 18.5mg of vitamin E per day vs. those with an average intake of 9mg per day.
Similar associations have been reported for vitamin D, in that insufficient intakes may accelerate age-related declines in cognitive performance. In new research, severe vitamin D deficiency, defined as blood levels of 25-hydroxyvitamin D (25(OH)D) of less than 25 nanomoles per liter, was associated with a 60% increase in the risk of substantial cognitive decline 17.
Also linked to cognitive function is the finding that deficiencies in antioxidant vitamin intake may be related to psychological abnormalities. Hospitalized patients receiving either vitamin C (500mg twice daily) showed a 34% reduction in mood swings18. Sub-normal vitamin C concentrations in the cerebrospinal fluid may adversely affect brain function and mood, according to the researchers.
Vitamin D and calcium intakes are associated with weight maintenance and, in some cases, weight loss. Data from NHANES (2001-2004), which included 9,757 children and adolescents ages 1-21 years, found serum vitamin D deficiency (<37.5nmol/L) in obese children compared to non-obese children19.
Similar observations have been noted in adults. In men of 50 years or less, those with a body mass index (BMI) of 20-24 had a mean serum 25(OH) D level of 85nmol/L compared to 59nmol/L for men with a BMI of 40+20. Similar inverse relationships between serum 25 (OH) D and BMI were reported in a cross-sectional evaluation of 1,606 elderly men21.
The association between higher dairy calcium intake and weight loss was first identified over a decade ago, and new research is confirming these observations. Using data from 322 subjects with a mean BMI of 31 and a mean age of 52 years, it was reported baseline serum 25(OH) D concentrations were significantly lower among those who had higher BMIs22. Further, higher 6-month levels of dairy calcium intake and serum 25(OH)D were correlated with increased weight loss across a 2-year intervention period. Individuals who averaged about 580mg per day of calcium lost about 12lbs, compared to about 7lbs for those with the lowest dairy calcium intake (about 150mg per day). A similar relationship was noted with serum vitamin D levels, the higher of which were associated with greater weight reduction.
While much of pre- and probiotic research is still focused on digestive and immune health, new research is exploring their effects on weight. In a placebo-controlled trial, 87 subjects with BMIs ranging from 24.2-30.7 and with high abdominal visceral fat area were randomly assigned to receive either fermented milk (FM) containing the probiotic Lactobacillus gasseri SBT2055 (LG2055) or FM without LG2055 for 12 weeks23. In those consuming the FM with LG2055, abdominal visceral and subcutaneous fat areas significantly decreased by an average of 4.6 and 3.3%, respectively. Significant decreases were also reported in the following parameters: body weight, 1.4%; BMI, 1.5%; waist, 1.8%; and hip, 1.5%.
Regarding omega-3 fatty acids, a diet with a high omega-6 to omega-3 ratio can lead to weight gain, which could be passed along to subsequent generations24. Male and female mice fed a high-fat diet with a 28:1 ratio produced offspring that, over four generations, showed gradual increases in fat mass, with no change in food intake or genetic pattern.
Emerging Research on Non-traditional Benefits of Supplementation
Increasingly, vitamin and mineral intakes are being assessed in relationship to conditions not usually associated with a nutrient deficiency. For example, novel research has reported that, in 247 adults with advanced fatty liver disease, high dose vitamin E (800IU) improved liver function by 43% compared with 19% in a placebo group25.
A review of randomized, controlled trials reported vitamins C and E and selenium may improve sperm quality and pregnancy rates, related again to oxidative stress, which can reduce the quality of sperm26. Some 75% of 17 trials, which included 1,665 men, showed antioxidant supplementation was associated with an improvement in at least one sperm parameter compared with placebo or no treatment. Significant improvements in sperm motility and enhanced sperm concentrations were noted in 60 and 30% of the studies, respectively. Further, antioxidant supplementation was associated with a 19% higher pregnancy rate in comparison to 3% in placebo or control groups.
Emerging research has identified that probiotics and prebiotics may reduce the incidence of a number of infant and childhood illnesses. In one clinical trial, 624 children aged between 1-3 years received either a control milk or the same milk fortified with B. lactis HN019 and prebiotic oligosaccharides (2.4g/day) 27. Following one year, there were significant reductions in the incidence of dysentery (21%), pneumonia (24%) and severe acute lower respiratory infection (35%), in the children receiving the synbiotic milk compared with the control group.
The probiotic Lactobacillus reuteri 17938 led to higher frequency of bowel movements at weeks 2, 4 and 8 of supplementation in infants28. The randomized study included 44 infants, 6 months old, who were diagnosed with functional chronic constipation. Because of a favorable safety profile, probiotics may be an option in the treatment of constipation and for children and adolescents with IBS.
Probiotics may also be beneficial in the management of inflammatory bowel disease (IBS) in children and teens, as determined by a clinical study with 59 children between the ages of 4-18 years, who had been diagnosed with IBS29. The participants were randomly assigned to receive either placebo or the probiotic supplement containing a combination of B. breve, B. longum, B. infantis, L. acidophilus, L. plantarum, L. paracasei, L. bulgaricus and Streptococcus thermophilus for 6 weeks. The supplement provided significant improvement in subjective assessment of relief of symptoms. Probiotics were also more effective than placebo in decreasing abdominal pain/discomfort, abdominal bloating/gassiness and family assessment of life disruption.
In other research, 65% of infants who received daily doses of B animalis subsp. Lactis BB-12 experienced respiratory illnesses, compared with 94% of infants in a control group30. The 109, 1-month-old infants were randomly assigned to the probiotic or placebo, up until the age of 8 months.
The combination of prebiotic fibers fructo-oligosaccharides (FOS) and resistant starch appear to favorably alter immune response31. Animals consumed the same diet, with one group receiving only drinking water; the other 3 groups were supplemented with either FOS (2g per rat per day), resistant starch (2g per rat per day) or a combination of both (2g per rat per day, 62.5% resistant starch, 37.5% FOS). This combination produced an up-regulation of genes linked to improved intestinal barrier function and provided intestinal anti-inflammatory effects associated with an increase of protective bacteria.
In another area of emerging research, fish oil omega-3s benefit type 2 diabetics by reducing triacylglycerol (TAG), a fatty substance linked to heart disease32. A supplement of 4g of fish oil for 8 weeks lowered TAG and also increased levels of "good" cholesterol HDL. The ratio of "bad" cholesterol LDL to HDL was also favorably decreased.
Researchers have long known certain compounds are critical to prevent simple nutritional deficiencies. As science evolves, knowledge of the importance of these nutrients for far-ranging and seemingly unrelated health conditions will grow. NS
1 Verhagen HB, et al. 2006. The state of antioxidant affairs. Nutr Today. 41:244-50.
2Mas E, et al. 2010. The omega-3 fatty acids EPA and DHA decrease plasma F(2)-isoprostanes: Results from two placebo-controlled interventions. Free Radic Res. 44(9): 983ñ990.
3 Carr AC and B Frei. 1999. Toward a new recommended dietary allowance for vitamin C based on antioxidant and health effects in humans. Amer J Clin Nutr. 69:1086-107.
4 Zhang S, et al. 1999. Dietary carotenoids and vitamins A, C, and E and risk of breast cancer. J Natl Cancer Inst. 91:547-56.
5 Park Y, et al. 2010. Intakes of vitamins A, C, and E and use of multiple vitamin supplements and risk of colon cancer: a pooled analysis of prospective cohort studies. 2010. Cancer Causes Control. [Epub ahead of print] doi: 10.1007/s10552-010-9549).
6 Lieberman DA, et al. 2003. Risk factors for advanced colonic neoplasia and hyperplastic polyps in asymptomatic individuals. JAMA 290:2959-67.
7 Lappe JM, et al. 2007. Vitamin D and calcium supplementation reduces cancer risk: results of a randomized trial. Amer J Clin Nutr.85:1586-91.
8 Yu W, et al. 2010. Dietary vitamin D exposure prevents obesity-induced increase in endometrial cancer in pten+/- mice. Cancer Prev Research. 3:1246-1258.
9 Patterson BH and OA Levander. 1997. Naturally occurring selenium compounds in cancer chemoprevention trials: A workshop summary. Cancer Epidemiol. Biomarkers Prev. 6:63-9.
10 Combs GF, Jr, et al. 1997. Reduction of cancer risk with an oral supplement of selenium. Biomed Environ Sci. 10:227-34.
11 White E, et al. 2010. Specialty supplements and breast cancer risk in the vitamins and lifestyle (VITAL) cohort. Cancer Epidemiol Biomarkers Prev. 19(7):1696-708.
12 Evans, JR. 2006. Antioxidant vitamin and mineral supplements for slowing the progression of age-related macular degeneration. Cochrane Database Syst Rev. [Epub ahead of print] (2):CD000254).
13 Age-Related Eye Disease Study Research Group. A randomized, placebo-controlled, clinical trial of high-dose supplementation with vitamins C and E, beta carotene and zinc for age-related macular degeneration and vision loss: AREDS report no. 8. 2001. Arch Ophthalmol. 119:1417-36.
14 van Leeuwen R, et al. 2005. Dietary intake of antioxidants and risk of age-related macular degeneration. JAMA. 294:3101-7.
15 Swenor BK, et al. 2010. The impact of fish and shellfish consumption on age-related macular degeneration. Ophthalmology. [Epub ahead of print.] doi:10.1016/j.ophtha.2010.03.058.
16 Devore EE, et al. 2010. Dietary antioxidants and long-term risk of dementia. Arch Neurology. 67(7): 819-825.
17 Llewellyn DJ, et al. 2010. Vitamin D and risk of cognitive decline in elderly persons. Archives of Intern Medicine. 170(13):1135-1141.
18 Zhang M, et al. 2010. Vitamin C provision improves mood in acutely hospitalized patients. Nutrition. Aug 4. [Epub ahead of print].
19 Reis JP, et al. 2009. Vitamin D status and cardiometabolic risk factors in the U.S. adolescent population. Pediatrics. 124(3):e371-9.
20 Brock K, et al. 2010. Low vitamin D status is associated with physical inactivity, obesity and low vitamin D intake in a large U.S. sample of healthy middle-aged men and women. J Steroid Biochem Mol Biol. 121(1-2):462-6).
21 Young KA, et al. 2009. Association of plasma vitamin D levels with adiposity in Hispanic and African-Americans. J Clin Endocrinol Metab. 94(9):3306-13.
22 Shahar DR, et al. 2010. Dairy calcium intake, serum vitamin D and successful weight loss. Amer J Clin Nutr. 2010 Sep 1. PMID: 2081097.
23 Kadooka Y, et al. 2010. Lactobacillus gasseri SBT2055 in adults with obese tendencies in a randomized controlled trial. Eur J Clin. Nutr 64(6):636-43).
24 Massiera, F, et al. 2010. A Western-like fat diet is sufficient to induce a gradual enhancement in fat mass over generations. J Lipid Res. 51:2352-2361.
25 Sanyal AJ, et al. 2010. Pioglitazone, vitamin E or placebo for nonalcoholic steatohepatitis. N Engl J Med. 6;362(18):1675-85.
26 Ross C, et al. 2010. A systematic review of the effect of oral antioxidants on male infertility. Reprod BioMedicine 20:711-723.
27 Sazawal S, et al. 2010. Prebiotic and probiotic fortified milk in prevention of morbidities among children: community-based, randomized, double-blind, controlled trial. PLoS ONE. 5(8):e12164.
28 Coccorullo P, et al. 2010. Lactobacillus reuteri (DSM 17938) in infants with functional chronic constipation: a double-blind, randomized, placebo-controlled study. J Pediatrics. 157(4):598-602).
29 Guandalini S, et al. 2010. VSL#3 improves symptoms in children with irritable bowel syndrome: a multicenter, randomized, placebo-controlled, double-blind, crossover study. J Pediatr Gastroenterol Nutr. 51(1):24-30.
30 Taipale T, et al. 2010 Bifidobacterium animalis subsp. lactis BB-12 in reducing the risk of infections in infancy. Br J Nutr. [Epub ahead of print] doi: 0.1017/S0007114510003685).
31 RodrÌguez-Cabezas ME, et al. 2010. The combination of fructo-oligosaccharides and resistant starch shows prebiotic additive effects in rats. Clin Nutr [Epub ahead of print] doi: 10.1016/j.clnu.2010.05.005).
32 Petersen M, et al. 2002. Effect of fish oil versus corn oil supplementation on LDL and HDL subclasses in type 2 diabetic patients. Diabetes Care. 25(10):1704-1708.