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Th1/Th2 balance: the hypothesis, its limitations, and implications for health and disease. Kidd P. Altern Med Rev. 2003 Aug;8(3):223-46. Review. PMID: 12946237 Th1 pathways typically produce activation of cytotoxic T lymphocytes (Tc), NK cells, macrophages, and monocytes, all of which can attack cancer cells and generally defend against tumors. 55 IFN-gamma and other Th1 cytokines are typically lower in advanced cancer patients, while the Th2 marker IL-4 can be higher or unchanged.56 Nodules of non-small cell lung cancer freshly removed from patients expressed a marked imbalance toward Th2, as did biopsy samples from basal cell carcinoma.57 In prostate cancer patients IL-2 was low (Th1) and IL-10 high.58 IL-10 is a confirmed Th1-suppressive cytokine, and heightened IL-10 is a common factor in cancer.55 IL-10 has a variety of suppressive effects that include inhibiting Th1 cytokine production, down-regulating APC and NK cell function, and lowering overall T-cell proliferation.57 Especially under the influence of IL-4 (Th2), tumor cells apparently up-regulate IL-10 that suppresses nearby killer cells. Tumor-derived IL-10 has been documented in lymphoma, ovarian carcinoma, melanoma, neuroblastoma, and renal cell and colon carcinoma.57 IL-12 is another cytokine that can be up-regulated by Th1 activity and inhibited by Th2.59 A low IL-12/IL-10 ratio was found in cervical cancer patients.55 Recent clinical studies suggest elevated IL-10 is predictive of a poor prognosis. 57 With both IL-4 and IL-10 being proven inhibitors of Th1 and promoters of Th2 activity, the recognized capability of cancerous tissue to suppress immunity is readily rationalized.

Vitamin D deficiency: a worldwide problem with health consequences. Holick MF, Chen TC. Am J Clin Nutr. 2008 Apr;87(4):1080S-6S. Review. PMID: 18400738 A reevaluation needs to take place of what the adequate intakes of vitamin D should be for children and adults. The literature over the past decade suggests that the Institute of Medicine recommendations in 1997 (83) are inadequate, and some experts including us suggest that both children and adults should take ≥800-1000 IU vitamin D/d from dietary and supplemental sources (4, 9, 77) when sunlight is unable to provide it. This recommendation, however, has not yet been embraced either by official government or pediatric organizations in the United States, Canada, or Europe for either children or adults.

Strategies to improve vitamin D status in northern European children: exploring the merits of vitamin D fortification and supplementation. Tylavsky FA, Cheng S, Lyytikäinen A, Viljakainen H, Lamberg-Allardt C. J Nutr. 2006 Apr;136(4):1130-4. PMID: 16549494

Relation of body fat indexes to vitamin D status and deficiency among obese adolescents. Lenders CM, Feldman HA, Von Scheven E, Merewood A, Sweeney C, Wilson DM, Lee PD, Abrams SH, Gitelman SE, Wertz MS, Klish WJ, Taylor GA, Chen TC, Holick MF; Elizabeth Glaser Pediatric Research Network Obesity Study Group. Am J Clin Nutr. 2009 Sep;90(3):459-67. Epub 2009 Jul 29. PMID: 19640956 RESULTS: The mean (+/-SD) age of the adolescents was 14.9 +/- 1.4 y; 38 (66%) were female, and 8 (14%) were black. The mean (+/-SD) body mass index (in kg/m(2)) was 36 +/- 5, FM was 40.0 +/- 5.5%, and VAT was 12.4 +/- 4.3%. Seventeen of the adolescents were vitamin D deficient, but none had elevated PTH concentrations. Bone mineral content and bone mineral density were within 2 SDs of national standards. In a multivariate analysis, 25(OH)D decreased by 0.46 +/- 0.22 ng/mL per 1% increment in FM (beta +/- SE, P = 0.05), whereas PTH decreased by 0.78 +/- 0.29 pg/mL per 1% increment in VAT (P = 0.01). CONCLUSIONS: To the best of our knowledge, our results show for the first time that obese adolescents with 25(OH)D deficiency, but without elevated PTH concentrations, have a bone mass within the range of national standards (+/-2 SD). The findings provide initial evidence that the distribution of fat may be associated with vitamin D status, but this relation may be dependent on metabolic factors

A recently published study in Nutrition and Cancer (60(5), 643-651) by researchers at Kansai Medical University in Osaka, Japan has shown that AHCC (Active Hexose Correlated Compound) enhances immune function by increasing the number of dendritic cells (DCs). DCs are a key part of the immune system responsible for presenting foreign substances to other immune system cells. The study was conducted in a double-blind randomized fashion where twenty-one healthy subjects received a placebo or AHCC at 3.0 g/day for 4 weeks. Blood samples were obtained and measured at baseline and at 4 weeks. The number of circulating types of DCs was measured which included CD 11c+ DCs (myeloid DC population; DC1) and CD11c- DCs (lymphoid DC population; DC2). Other parameters measured included mixed-leukocyte reaction (MLR), natural killer (NK) cell activity, the proliferative response of T lymphocytes toward mitogen (phytohemagglutinin [PHA]) and cytokine production of interleukin (IL)-2, IL-4, IL-6, IL-10, interferon gamma-gamma, and (alpha)-tumor necrosis factor.

Soy Food Intake and Breast Cancer Survival. Xiao Ou Shu et al. JAMA Vol. 302 No. 22, December 9, 2009; 302(22):2437-2443. Results During the median follow-up of 3.9 years (range, 0.5-6.2 years), 444 deaths and 534 recurrences or breast cancer-related deaths were documented in 5033 surgically treated breast cancer patients. Soy food intake, as measured by either soy protein or soy isoflavone intake, was inversely associated with mortality and recurrence. The hazard ratio associated with the highest quartile of soy protein intake was 0.71 (95% confidence interval [CI], 0.54-0.92) for total mortality and 0.68 (95% CI, 0.54-0.87) for recurrence compared with the lowest quartile of intake. The multivariate-adjusted 4-year mortality rates were 10.3% and 7.4%, and the 4-year recurrence rates were 11.2% and 8.0%, respectively, for women in the lowest and highest quartiles of soy protein intake. The inverse association was evident among women with either estrogen receptor-positive or -negative breast cancer and was present in both users and nonusers of tamoxifen. Conclusion Among women with breast cancer, soy food consumption was significantly associated with decreased risk of death and recurrence.

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Cardiovascular risk and alpha-linolenic acid: can Costa Rica clarify? Harris WS. Circulation. 2008 Jul 22;118(4):323-4. Epub 2008 Jul 7. Review. PMID: 18606912 doi: 10.1161/CIRCULATIONAHA.108.791467

"18 645 patients with a total cholesterol of 6·5 mmol/L or greater were recruited from local physicians throughout Japan between 1996 and 1999. Patients were randomly assigned to receive either 1800 mg of EPA daily with statin (EPA group; n=9326) or statin only (controls; n=9319) with a 5-year follow-up. The primary endpoint was any major coronary event, including sudden cardiac death, fatal and non-fatal myocardial infarction, and other non-fatal events including unstable angina pectoris, angioplasty, stenting, or coronary artery bypass grafting. Analysis was by intention-to-treat. Findings At mean follow-up of 4·6 years, we detected the primary endpoint in 262 (2·8%) patients in the EPA group and 324 (3·5%) in controls-a 19% relative reduction in major coronary events (p=0·011). Post-treatment LDL cholesterol concentrations decreased 25%, from 4·7 mmol/L in both groups. Serum LDL cholesterol was not a significant factor in a reduction of risk for major coronary events. Unstable angina and non-fatal coronary events were also significantly reduced in the EPA group. Sudden cardiac death and coronary death did not differ between groups. In patients with a history of coronary artery disease who were given EPA treatment, major coronary events were reduced by 19% (secondary prevention subgroup: 158 [8·7%] in the EPA group vs 197 [10·7%] in the control group; p=0·048). In patients with no history of coronary artery disease, EPA treatment reduced major coronary events by 18%, but this finding was not significant (104 [1·4%] in the EPA group vs 127 [1·7%] in the control group; p=0·132)."

Egg consumption in relation to cardiovascular disease and mortality: the Physicians' Health Study. Djoussé L, Gaziano JM. Am J Clin Nutr. 2008 Apr;87(4):964-9. PMID: 18400720 Results: In an average follow-up of 20 y, 1550 new myocardial infarctions (MIs), 1342 incident strokes, and 5169 deaths occurred. Egg consumption was not associated with incident MI or stroke in a multivariate Cox regression. In contrast, adjusted hazard ratios (95% CI) for mortality were 1.0 (reference), 0.94 (0.87, 1.02), 1.03 (0.95, 1.11), 1.05 (0.93, 1.19), and 1.23 (1.11, 1.36) for the consumption of < 0.0001). This association was stronger among diabetic subjects, in whom the risk of death in a comparison of the highest with the lowest category of egg consumption was twofold (hazard ratio: 2.01; 95% CI: 1.26, 3.20; P for interaction = 0.09). Conclusions: Infrequent egg consumption does not seem to influence the risk of CVD in male physicians. In addition, egg consumption was positively related to mortality, more strongly so in diabetic subjects, in the study population.

Menaquinone-4 concentration is correlated with sphingolipid concentrations in rat brain. Carrié I, Portoukalian J, Vicaretti R, Rochford J, Potvin S, Ferland G. J Nutr. 2004 Jan;134(1):167-72. PMID: 14704312

Weston Price established the importance of the MK-4 isoform of vitamin K2 (hereafter, K2) with a series of interesting experiments. He showed in chickens that blood levels of calcium and phosphorus depended both on vitamin A and K2, and that the two had synergistic effects on mineral absorption. He also showed that chickens preferred eating butter that was rich in K2 over butter low in K2, even when the investigators couldn't distinguish between them. Young turkeys fed K2-containing butter oil along with cod liver oil (A and D) also grew at a much faster rate than turkeys fed cod liver oil alone.

Tissue phylloquinone and menaquinones in rats are affected by age and gender. Huber AM, Davidson KW, O'Brien-Morse ME, Sadowski JA. J Nutr. 1999 May;129(5):1039-44. PMID: 10222397 The results suggest that in extrahepatic tissues, certain menaquinones may be the predominant form of vitamin K. The specific tissue distribution and the general decline of MK-4 and MK-6 in extrahepatic tissues during aging suggest a vitamin K tissue dynamic that is affected not only by diet, but also by gender, age and the specific roles of phylloquinone, MK-4 and MK-6 in metabolism. All of these factors must be taken into account in establishing the nutrient requirement for vitamin K.

A randomised comparison of increase in serum 25-hydroxyvitamin D concentration after 4 weeks of daily oral intake of 10 microg cholecalciferol from multivitamin tablets or fish oil capsules in healthy young adults. Holvik K, Madar AA, Meyer HE, Lofthus CM, Stene LC. Br J Nutr. 2007 Sep;98(3):620-5. Epub 2007 Apr 24. PMID: 17456248 We conclude that fish oil capsules and multivitamin tablets containing 10 microg cholecalciferol administered over a 4-week period produced a similar mean increase in s-25(OH)D concentration.

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Dietary mono- and polyunsaturated fatty acids similarly affect LDL size in healthy men and women. Kratz M, Gülbahçe E, von Eckardstein A, Cullen P, Cignarella A, Assmann G, Wahrburg U. J Nutr. 2002 Apr;132(4):715-8. PMID: 11925466 In conclusion, our data indicate that dietary unsaturated fat similarly reduces LDL size relative to saturated fat. However, the small magnitude of this reduction also suggests that the composition of dietary fat is not a major factor affecting LDL size.

Consumption of 2 and 4 egg yolks/d for 5 wk increases macular pigment concentrations in older adults with low macular pigment taking cholesterol-lowering statins. Vishwanathan R, Goodrow-Kotyla EF, Wooten BR, Wilson TA, Nicolosi RJ. Am J Clin Nutr. 2009 Nov;90(5):1272-9. Epub 2009 Sep 16. PMID: 19759170 Conclusions: Consumption of 4 egg yolks/d, and possibly of 2 egg yolks/d, for 5 wk benefited macular health in older adults with low MPOD. Serum HDL cholesterol increased without an increase in LDL cholesterol in this study population, most of whom were taking cholesterol-lowering statins.

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