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Vitamin D intake to attain a desired serum 25-hydroxyvitamin D concentration. Aloia JF, Patel M, Dimaano R, Li-Ng M, Talwar SA, Mikhail M, Pollack S, Yeh JK. Am J Clin Nutr. 2008 Jun;87(6):1952-8. PMID: 18541590 The mean daily dose was 86 microg (3440 IU). The use of computer simulations to obtain the most participants within the range of 75-220 nmol/L predicted an optimal daily dose of 115 microg/d (4600 IU). No hypercalcemia or hypercalciuria was observed. CONCLUSIONS: Determination of the intake required to attain serum 25(OH)D concentrations >75 nmol/L must consider the wide variability in the dose-response curve and basal 25(OH)D concentrations. Projection of the dose-response curves observed in this convenience sample onto the population of the third National Health and Nutrition Examination Survey suggests a dose of 95 microg/d (3800 IU) for those above a 25(OH)D threshold of 55 nmol/L and a dose of 125 microg/d (5000 IU) for those below that threshold.

Randomized comparison of the effects of the vitamin D3 adequate intake versus 100 mcg (4000 IU) per day on biochemical responses and the wellbeing of patients. Vieth R, Kimball S, Hu A, Walfish PG. Nutr J. 2004 Jul 19;3:8. PMID: 15260882 doi:10.1186/1475-2891-3-8 CONCLUSION: The highest AI for vitamin D brought summertime 25(OH)D to >40 nmol/L, lowered PTH, and its use was associated with improved wellbeing. The 100 mcg/day dose produced greater responses. Since it was ethically necessary to provide a meaningful dose of vitamin D to these insufficient patients, we cannot rule out a placebo wellbeing response, particularly for those on the lower dose. This work confirms the safety and efficacy of both 15 and 100 mcg/day vitamin D3 in patients who needed additional vitamin D.

Dose response to vitamin D supplementation among postmenopausal African American women.\nTalwar SA, Aloia JF, Pollack S, Yeh JK.\nAm J Clin Nutr. 2007 Dec;86(6):1657-62.\nPMID: 18065583

Together, the earlier data and the data of Heaney et al indicate that an oral dose of vitamin D2 or vitamin D3 would lead to a comparable increase in circulating 25(OH)D concentrations in children and adults when the initial 25(OH)D3 concentrations in the groups are similar and when equivalent oral vitamin D doses expressed per kilogram body weight/d are given. Serum 25-hydroxyvitamin D response to oral vitamin D intake in children. Zittermann A. Am J Clin Nutr. 2003 Sep;78(3):496-7. PMID: 12936937

How much vitamin D3 do the elderly need? Viljakainen HT, Palssa A, Kärkkäinen M, Jakobsen J, Lamberg-Allardt C. J Am Coll Nutr. 2006 Oct;25(5):429-35. PMID: 17031013 Conclusions: A clear dose response was noted in S-25-OHD to different doses of vitamin D3. The recommended dietary intake of 15 µg is adequate to maintain the S-25-OHD concentration around 40-55 nmol/L during winter, but if the optimal S-25-OHD is higher than that even higher vitamin D intakes are needed. Interestingly, subjects with lower vitamin D status at baseline responded more efficiently to supplementation than those with more adequate status

Conclusion: Vitamin D3 at doses equivalent to 2000 IU/d for 1 yr is safe in adolescents and results in desirable vitamin D levels. Short- and long-term safety of weekly high-dose vitamin D3 supplementation in school children. Maalouf J, Nabulsi M, Vieth R, Kimball S, El-Rassi R, Mahfoud Z, El-Hajj Fuleihan G. J Clin Endocrinol Metab. 2008 Jul;93(7):2693-701. Epub 2008 Apr 29. PMID: 18445674 doi:10.1210/jc.2007-2530

Combination immunotherapy of squamous cell carcinoma of the head and neck: a phase 2 trial. Barrera JL, Verastegui E, Meneses A, Zinser J, de la Garza J, Hadden JW. Arch Otolaryngol Head Neck Surg. 2000 Mar;126(3):345-51. PMID: 10722007 The natural cytokine mixture is a collection of natural human cytokines induced from human peripheral blood mononuclear cells. It contains IL-1, IL-2, IL-6, IL-8, IL-10, IL-12, interferon gamma, tumor necrosis factor , and granulocyte-macrophage and granulocyte colony-stimulating factor in nanogram quantities. It lacks IL-3, IL-4, IL-5, and IL-7. [...] This IRX-2 strategy uses perilymphatic local administration along with contrasuppression with low-dose cyclophosphamide and indomethacin and with zinc replacement therapy (as an immunorestorative). The data presented herein demonstrate that H&N SCC can respond very well to immunotherapy: there was a response rate of 100% in this series of 15 patients, with clinical reduction in tumor (1 complete response, 7 partial responses, and 7 minor responses) and histological evidence of tumor regression of 42%. Overall, the average combined estimated tumor reduction exceeded 70%. Also, patients with oral cancer noted marked analgesic and hemostatic effects from this therapy, with healing of oral lesions. [...] It is important to note that adjuvant chemotherapy is not used at INCAN. Many studies23 indicate that treatment with fluorouracil and cisplatin, the combination most in use, is effective for reducing tumors in the majority of patients; however, with no meaningful impact on survival, their routine use in the United States has recently been questioned.24-25 The expense, toxic effects, and lack of effectiveness of both drugs has made their use in other less affluent countries unwarranted. The current data on the use of IRX-2 in this and other protocols8-10 hint at improved survival, and a phase 3 randomized controlled study comparing this protocol with chemotherapy arm is to be initiat

Human serum 25-hydroxycholecalciferol response to extended oral dosing with cholecalciferol. Heaney RP, Davies KM, Chen TC, Holick MF, Barger-Lux MJ. Am J Clin Nutr. 2003 Jan;77(1):204-10. Erratum in: Am J Clin Nutr. 2003 Nov;78(5):1047. PMID: 12499343

"THURSDAY, Dec. 17 (HealthDay News) -- In a surprise finding, Canadian researchers report that the immediate effect of the fish oil fatty acids that are good for the heart is a short-term increase in blood fats and the molecules that help them form clots. "We were surprised to find that the acute response has some potentially negative effects in comparison to what you might expect from chronic, long-term intake," said Lindsay E. Robinson, an associate professor of nutrition at the University of Guelph, and leader of the group reporting the finding in the January issue of the Journal of Nutrition. However, the study results shouldn't affect the current recommendation for eating more oily fish to get the omega-3 polyunsaturated acids that reduce the risk of blood clots that can cause heart attacks and stroke, Robinson said. "The recommendation to increase intake is very well-studied, and this doesn't change it," she said. And the effects were seen in a selected group of middle-aged men with metabolic syndrome, a combination of high blood pressure, obesity and elevated blood fat levels, Robinson noted. In the study, eight men had controlled intake of three regimens: high doses of omega-3 fatty acids, low doses of them and just plain water. Robinson and her colleagues measured several blood components involved in clotting, including fats and clotting factors such as plasminogen-activator inhibitor-1 (PAI-1) for the following eight hours. PAI-1 inhibits the destruction of blood clots, so high levels of it in the blood increase the risk of artery-blocking clots. The researchers found that both omega-3 fatty acid regimens increased blood fat and clotting factor activity. But the increase in clotting factor was greater for the higher doses of omega-3 fatty acids than for the lower intakes. Robinson said her group hopes to do further studies of the immediate effects of omega-3 fatty acid intake. "We need to look at the mechanisms, why blood lipid levels go up," she

A positive dose-response effect of vitamin D supplementation on site-specific bone mineral augmentation in adolescent girls: a double-blinded randomized placebo-controlled 1-year intervention. Viljakainen HT, Natri AM, Kärkkäinen M, Huttunen MM, Palssa A, Jakobsen J, Cashman KD, Mølgaard C, Lamberg-Allardt C. J Bone Miner Res. 2006 Jun;21(6):836-44. PMID: 16753014 doi: 10.1359/jbmr.060302 We conclude that the current vitamin D recommendation for adolescent girls, at least in the northern latitudes, is too low to ensure sufficient vitamin D status during winter. Intake of vitamin D at rates of 10-15 μg/day aids to maintain stable S-25(OH)D concentrations during winter. Vitamin D induced BMC augmentation by decreasing bone resorption, but not affecting bone formation, which was reflected by the biochemical markers of bone turnover. Optimizing bone mineral gain in adolescence is crucial to the prevention of osteoporosis later in life. Increasing vitamin D intake to 10-15 μg/day aids in attaining this goal.

Low-dose supplementation with active hexose correlated compound improves the immune response to acute influenza infection in C57BL/6 mice. Nogusa S, Gerbino J, Ritz BW. Nutr Res. 2009 Feb;29(2):139-43. PMID: 19285605 doi:10.1016/j.nutres.2009.01.005

Effects of pistachios on cardiovascular disease risk factors and potential mechanisms of action: a dose-response study. Gebauer SK, West SG, Kay CD, Alaupovic P, Bagshaw D, Kris-Etherton PM. Am J Clin Nutr. 2008 Sep;88(3):651-9. PMID: 18779280

Serum vitamin D concentration and prostate cancer risk: a nested case-control study. Ahn J, Peters U, Albanes D, Purdue MP, Abnet CC, Chatterjee N, Horst RL, Hollis BW, Huang WY, Shikany JM, Hayes RB; Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial Project Team. J Natl Cancer Inst. 2008 Jun 4;100(11):796-804. Epub 2008 May 27. PMID: 18505967 doi:10.1093/jnci/djn152 CONCLUSION: The findings of this large prospective study do not support the hypothesis that vitamin D is associated with decreased risk of prostate cancer; indeed, higher circulating 25(OH)D concentrations may be associated with increased risk of aggressive disease. In summary, results from this large prospective study of men who underwent standardized prostate cancer screening in the context of a screening trial do not support the hypothesis that higher serum vitamin D status is associated with decreased risk of prostate cancer. The study showed no association of vitamin D level with nonaggressive disease; however, it raises the possibility that higher vitamin D level may be associated with increased risks for aggressive disease, although a clear monotonic dose-response relationship was lacking. Along with recent reports of adverse associations for higher vitamin D status and risk of pancreatic (32) and esophageal (33,34) cancer, caution should be taken in recommending high doses of vitamin D or sunlight exposure to the general public for prostate cancer prevention. Future analyses are warranted to confirm these results and to further clarify the effects of vitamin D on aggressive prostate cancer.

Jenkins DJ, Kendall CW, Marchie A, Parker TL, Connelly PW, Qian W, Haight JS, Faulkner D, Vidgen E, Lapsley KG, Spiller GA. Dose response of almonds on coronary heart disease risk factors: blood lipids, oxidized low-density lipoproteins, lipoprotein(a),

Consumption of cod and weight loss in young overweight and obese adults on an energy reduced diet for 8-weeks. Ramel A, Jonsdottir MT, Thorsdottir I. Nutr Metab Cardiovasc Dis. 2009 Dec;19(10):690-6. Epub 2009 Apr 8. PMID: 19356912 Conclusion A dose-response relationship between cod consumption and weight loss during an 8-week energy restriction diet is found and 5×150g cod/week results in 1.7kg greater weight loss in young overweight or obese adults than a isocaloric diet without seafood

BACKGROUND: To determine the effect of vitamin D binding protein (DBP) genotypes on 25-hydroxyvitamin D [25(OH)D] changes with vitamin D supplements, we studied 98 adults receiving 600 or 4000 IU/d vitamin D(3) for one year. METHODS: The DBP functional variant, T436K, was genotyped by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). RESULTS: Mean 25(OH)D increases were 97% for TT (n=48), 151% for TK (n=31) and 307% (n=6) for KK genotypes (p=.004). CONCLUSIONS: As with baseline 25(OH)D, T436K genotype predicts 25(OH)D changes after long-term vitamin D supplementation. Common genetic variants of the vitamin D binding protein (DBP) predict differences in response of serum 25-hydroxyvitamin D [25(OH)D] to vitamin D supplementation. Fu L, Yun F, Oczak M, Wong BY, Vieth R, Cole DE. Clin Biochem. 2009 Jul;42(10-11):1174-7. Epub 2009 Mar 18. PMID: 19302999

YouTube - Vitamin D and Cancer Prevention. A presentation by Dr. Cedric Garland.

"So why is Dr Vieth so frustrated? You might think he'd have cause for celebration. But for him and other vitamin D researchers around the world, the good news comes with a bitter aftertaste. They believe they can prove vitamin D could help millions live longer and be healthier and yet they have not been able to convince their own governments. In the US and Canada, official vitamin D policy is set by the Institute of Medicine. And in the opinion of Vieth, the current recommendations - 200 International Units per day for people under 50, 400 for people aged 51-70, and 600 for those 71 and older - are outrageously low. Bruce Hollis, professor of paediatrics at the Medical University of South Carolina, calls 400 IU a day "a joke". That's because the best research suggests that to achieve the higher vitamin D blood levels associated with disease prevention, most adults in the US would need to take 1,000-2,000 IU a day: five to 10 times more than the current official recommendation for adult In 1999, Reinhold Vieth (pictured right) published a review of vitamin D research in response to the IOM conclusions. In it, he argued that there was no evidence that amounts lower than 20,000 IU a day could be toxic. "Throughout my preparation of this review, I was amazed at the lack of evidence supporting statements about the toxicity of moderate doses of vitamin D," Vieth wrote. Studies have since shown 10,000 IU a day of vitamin D to be safe. While any substance will become toxic in excess, vitamin D researchers today accept that the current vitamin D recommendations could be more than quadrupled with no fear of toxicity.!

"Derived from the root of the plant. This supplement is used in traditional Chinese medicine primarily for gastrointestinal complaints, diarrhea, hypertension, bacterial and viral infections. Berberine and berberine-like alkaloids are thought responsible for its activity (1). Laboratory studies indicate that berberine induces morphological changes and internucleosomal DNA fragmentation in hepatoma cancer cells (3). Preliminary data support the hypothesis that huanglian suppresses cyclin B1 protein and causes cell cycle arrest at G2 (5). Huanglian has potent antiangiogenesis activity (6). It also interacts with acetylcholine and muscarinic receptors and inhibits cholinesterase. Possible adverse effects include nausea and vomiting (1). Theoretically huanglian may have additive hypotensive effects with antihypertensive agents. A phase I dose escalation study of huanglian in solid tumors is currently underway at Memorial Sloan-Kettering Cancer Center based on"

Vitamin D and Cancer Mini-Symposium: The Risk of Additional Vitamin D. Vieth R. Ann Epidemiol. 2009 Apr 11. [Epub ahead of print] PMID: 19364661 doi:10.1016/j.annepidem.2009.01.009