Nutrition

"Measuring the number of small LDL particles is the best index of carbohydrate intake I know of, better than even blood sugar and triglycerides. In other words, increase carbohydrate intake and small LDL particles increase. Decrease carbohydrates and small LDL particles decrease. Why? Carbohydrates increase small LDL via a multistep process: First step: Increased fatty acid and apoprotein B production in the liver, which leads to increased VLDL production. (Apoprotein B is the principal protein of VLDL and LDL) Second step: Greater VLDL availability causes triglyceride-rich VLDL to interact with other particles, namely LDL and HDL, enriching them in triglycerides (via the action of cholesteryl-ester transfer protein, or CETP). Much VLDL is converted to LDL. Third step: Triglyceride-rich LDL is "remodeled" by enzymes like hepatic lipase, which create small LDL"

"ANN ARBOR, Mich. - A new study finds that compounds derived from the spices turmeric and pepper could help prevent breast cancer by limiting the growth of stem cells, the small number of cells that fuel a tumor's growth. Researchers at the University of Michigan Comprehensive Cancer Center have found that when the dietary compounds curcumin, which is derived from the Indian spice turmeric, and piperine, derived from black peppers, were applied to breast cells in culture, they decreased the number of stem cells while having no effect on normal differentiated cells. "If we can limit the number of stem cells, we can limit the number of cells with potential to form tumors," says lead author Madhuri Kakarala, M.D., Ph.D., R.D., clinical lecturer in internal medicine at the U-M Medical School and a research investigator at the VA Ann Arbor Healthcare System."

"A large 10-year study found that half of all fatal heart disease cases and a quarter of all non-fatal cases are linked to being overweight and having a high body mass index (BMI) or large waist. Body mass index and waist circumference are well known risk factors for cardiovascular diseases but the Dutch researchers said their work showed BMI and waist size could actually help predict the risk of dying from or developing heart disease."

Role of vitamin K2 in the treatment of postmenopausal osteoporosis. Iwamoto J, Takeda T, Sato Y. Curr Drug Saf. 2006 Jan;1(1):87-97. Review. PMID: 18690918

[Vitamin K2] Ishida Y. Clin Calcium. 2008 Oct;18(10):1476-82. Review. Japanese. PMID: 18830045 "Vitamin K2 has been approved for the treatment of osteoporosis in Japan since 1995. Vitamin K2 treatment in osteoporosis has been shown to inhibit the occurrence of new bone fractures and to maintain BMD. The uniqueness of the prevention of bone fractures by vitamin K2 is that there has been no direct evidence of the relationship between increase of BMD and a decrease in the occurrence of bone fractures. A recent systematic review of seven Japanese randomized controlled trials by Cockayne has also shown that supplementation with phytonadione (Vitamin K1) and menaquinone (Vitamin K2) , particularly menaquinone-4, is associated with increased BMD and reduced fracture incidence. To confirm these results, a larger well design RCT using fractures as the primary endpoint is clearly needed."

Effect of low dose vitamin K2 (MK-4) supplementation on bio-indices in postmenopausal Japanese women. Koitaya N, Ezaki J, Nishimuta M, Yamauchi J, Hashizume E, Morishita K, Miyachi M, Sasaki S, Ishimi Y. J Nutr Sci Vitaminol (Tokyo). 2009 Feb;55(1):15-21. PMID: 19352059 It has been reported that treatment with a pharmacological dose (45 mg/d) of menaquinone-4 (MK-4) prevents bone loss in postmenopausal women. However, it is not known whether supplementation with low dose MK-4 has beneficial effects on bone metabolism in healthy women. The aim of this study is to examine the effects of the supplementation of 1.5 mg/d MK-4 for 4 wk on bone and lipid metabolism in healthy postmenopausal Japanese women. The study was performed as a randomized double blind placebo-controlled trial. The participants aged 53-65 y were randomly assigned to 2 groups and supplemented with 1.5 mg/d of MK-4 or a placebo for 4 wk (n=20 for each group). The most marked effects of MK-4 intake were observed on serum osteocalcin (OC) concentrations. Serum undercarboxylated OC (ucOC) concentration decreased, and the gamma-carboxylated OC (GlaOC) and GlaOC/GlaOC+ucOC ratio that indicates the degree of OC gamma-carboxylation increased significantly at 2 and 4 wk compared with that at baseline in the MK-4 group. The serum ucOC and GlaOC concentrations in the MK-4 group were significantly different from those in the placebo group at 2 wk. These results suggest that supplementation with 1.5 mg/d MK-4 accelerated the degree of OC gamma-carboxylation. The concentrations of serum lipids and other indices were not different between the groups at either intervention period. Thus, the additional intake of MK-4 might be beneficial in the maintenance of bone health in postmenopausal Japanese women.

Combination of vitamin K2 and angiotensin-converting enzyme inhibitor ameliorates cumulative recurrence of hepatocellular carcinoma. Yoshiji H, Noguchi R, Toyohara M, Ikenaka Y, Kitade M, Kaji K, Yamazaki M, Yamao J, Mitoro A, Sawai M, Yoshida M, Fujimoto M, Tsujimoto T, Kawaratani H, Uemura M, Fukui H. J Hepatol. 2009 Aug;51(2):315-21. Epub 2009 May 15. PMID: 19501932 CONCLUSIONS: The combination treatment of VK and ACE-I may suppress the cumulative recurrence of HCC after the curative therapy, at least partly through suppression of the VEGF-mediated neovascularization.

[Vitamin K and Bone Update. In vivo Metabolism of Vitamin K. - In relation to the conversion of vitamin K(1) to MK-4 -] Okano T, Nakagawa K, Kamao M. Clin Calcium. 2009 Dec;19(12):1779-87. Japanese. PMID: 19949269 Phylloquinone is a major form (>90%) of dietary vitamin K, but the form of vitamin K that exists at the highest concentrations in tissues of animals and humans is menaquinone-4 (MK-4) . Despite this great difference, the origin of tissue MK-4 had not been clarified until recently. We demonstrated that deuterium-labeled phylloquinone was converted into deuterium-labeled MK-4 in mice and this conversion occurred following an oral or enteral administration, but not parenteral administration. By the oral route, the phylloquinone with the deuterium-labeled side chain (phytyl side-chain) was clearly converted into menaquinone-4 with a non-deuterium-labeled side chain (geranylgeranyl side-chain) , implying that phylloquinone was converted into menaquinone-4 via integral side-chain removal. Our results suggest that cerebral menaquinone-4 originates from phylloquinone intake and the release of menadione from phylloquinone in the intestine followed by the prenylation of menadione into menaquinone-4 in the intestine or tissues

Vitamin K content of foods and dietary vitamin K intake in Japanese young women. Kamao M, Suhara Y, Tsugawa N, Uwano M, Yamaguchi N, Uenishi K, Ishida H, Sasaki S, Okano T. J Nutr Sci Vitaminol (Tokyo). 2007 Dec;53(6):464-70. PMID: 18202532 Several reports indicate an important role for vitamin K in bone health as well as blood coagulation. However, the current Adequate Intakes (AI) might not be sufficient for the maintenance of bone health. To obtain a closer estimate of dietary intake of phylloquinone (PK) and menaquinones (MKs), PK, MK-4 and MK-7 contents in food samples (58 food items) were determined by an improved high-performance liquid chromatography method. Next, we assessed dietary vitamin K intake in young women living in eastern Japan using vitamin K contents measured here and the Standard Tables of Food Composition in Japan. PK was widely distributed in green vegetables and algae, and high amounts were found in spinach and broccoli (raw, 498 and 307 microg/100 g wet weight, respectively). Although MK-4 was widely distributed in animal products, overall MK-4 content was lower than PK. MK-7 was observed characteristically in fermented soybean products such as natto (939 microg/100 g). The mean total vitamin K intake of all subjects (using data from this study and Japanese food composition tables) was about 230 microg/d and 94% of participants met the AI of vitamin K for women aged 18-29 y in Japan, 60 microg/d. The contributions of PK, MK-4 and MK-7 to total vitamin K intake were 67.7, 7.3 and 24.9%, respectively. PK from vegetables and algae and MK-7 from pulses (including fermented soybean foods) were the major contributors to the total vitamin K intake of young women living in eastern Japan

"As far as I can tell, MK-4 is capable of performing all the functions of vitamin K. MK-4 can even activate blood clotting factors, which is a role traditionally ascribed to vitamin K1. Babies are often born clotting deficient, which is why we give newborns vitamin K1 injections in the U.S. to prevent hemorrhaging. In Japan, they give children MK-4 to prevent hemorrhage, an intervention that is very effective. Could that have to do with the fact that Japan has half the infant mortality rate of the U.S.? Today, I found another difference between MK-4 and MK-7. I was reading a paper about SXR-independent effects of vitamin K2 on gene expression. The investigators found that MK-4 strongly activates transcription of two specific genes in osteoblast cells. Osteoblasts are cells that create bone tissue. The genes are GDF15 and STC2 and they're involved in bone and cartilage formation. They tested K1 and MK-7, and in contrast to MK-4, they did not activate transcription of the genes in the slightest. This shows that MK-4 has effects on gene expression in bone tissue that MK-7 doesn't have. That being said, MK-7 may still have a place in a healthy diet. Just because it can't do everything MK-4 can, doesn't mean it has no role. It may be able to fill in for MK-4 in some functions, or reduce the dietary need for MK-4. But no one really knows at this point. Hunter-gatherers would have had a source of longer menaquinones, including MK-7, from livers. So it's possible that we're adapted to a modest MK-7 intake on top of MK-4. "

Effect of vitamin K2 (menaquinone-7) in fermented soybean (natto) on bone loss in ovariectomized rats. Yamaguchi M, Taguchi H, Gao YH, Igarashi A, Tsukamoto Y. J Bone Miner Metab. 1999;17(1):23-9. PMID: 10084398 This study demonstrates that the intake of dietary MK-7 has a preventive effect on bone loss caused by OVX. This effect may be partly caused by MK-4, which is formed by degradation of MK-7.

Benefits of Vitamin D Supplementation Joel M. Kauffman, Ph.D. Journal of American Physicians and Surgeons Volume 14 Number 2 - Summer 2009 Clinical trials show that vitamin D supplementation at higher levels than previously recommended is beneficial for many conditions. It decreases the frequency of falls and fractures, helps prevent cardiovascular disease, and reduces symptoms of colds or influenza. Benefits are also seen in diabetes mellitus, multiple sclerosis, Crohn disease, pain, depression, and possibly autism. Sunlight does not cause an overdose of vitamin D production, and toxicity from supplementation is rare. Dose recommendations are increasing, but appear to be lagging the favorable trial results. A number of common drugs deplete vitamin D levels, and others may limit its biosynthesis from sunlight. People with adequate levels from sun exposure will not benefit from supplementation. While dietary intake is helpful, supplementation is better able to raise serum 25-hydroxyvitamin D , the major circulating metabolite, to the level now thought adequate, 30-50 ng/mL. Where there is inadequate daily sun exposure, oral doses of 1,000-2,000 IU/d are now considered routine, with much higher doses (up to 50,000 IU) for rapid repletion now considered safe.

"THURSDAY, Dec. 3 (HealthDay News) -- New research points to the possibility of a genetic link between vitamin D and heart disease. People with high blood pressure who had a gene variant that reduces vitamin D activation in the body were found to be twice as likely as those without the variant to have congestive heart failure, the study found. The finding may lead to a way to identify people at increased risk for heart disease, according to Robert U. Simpson, an assistant professor of pharmacology at the University of Michigan Medical School and his research colleagues. They analyzed the genetic profiles of 617 people. One-third had hypertension, one-third had hypertension and congestive heart failure, and the remaining third served as healthy controls. The researchers found that a variant in the CYP27B1 gene was associated with congestive heart failure in people with hypertension. The study is in the November issue of Pharmacogenomics."

A systematic review of the anticancer properties of berberine, a natural product from Chinese herbs. Sun Y, Xun K, Wang Y, Chen X. Anticancer Drugs. 2009 Oct;20(9):757-69. PMID: 19704371

"Today, goldenseal is marketed as a tonic to aid digestion, sooth upset stomach, and as an antibacterial and antiviral agent. It is considered a natural antibiotic and is most often combined with echinacea in preparations designed to strengthen the immune system. Many professional herbalists recommend goldenseal in herbal remedies for hay fever (also called allergic rhinitis), colds, and the flu. Goldenseal is considered a useful antiseptic (which is why some herbalists use it topically to disinfect cuts and scrapes) and astringent. It is commonly used to treat severak skin, eye, and mucous membrane inflammatory and infectious conditions (such as sinusitis, conjunctivitis, and urinary tract infections). It is also available in mouthwashes for sore throats and canker sores. Goldenseal has not been thoroughly investigated in scientific studies, but some trials have looked at berberine, one of the active compounds in goldenseal. Berberine is a substance widely used in Traditional Chinese Medicine to treat dysentery and infectious diarrhea. Berberine may be effective in humans for malaria, heart failure, and various types of infections, including upper respiratory problems."

Some medications are changed and broken down by the liver. Berberine might decrease how quickly the liver breaks down some medications. Taking berberine along with some medications that are broken down by the liver can increase the effects and side effects of some medications. Before taking berberine, talk to your healthcare provider if you are taking any medications that are changed by the liver. Some medications changed by the liver include cyclosporin (Neoral, Sandimmune), lovastatin (Mevacor), clarithromycin (Biaxin), indinavir (Crixivan), sildenafil (Viagra), triazolam (Halcion), and many others."

"Possible effects of berberine, a chemical found in small amounts in goldenseal, include headache, slow heart rate, nausea, vomiting, abdominal bloating, and low white blood cell count. It is not clear if the amount of berberine in goldenseal products is enough to cause these reactions. Toxic doses of berberine may cause seizures or irritation of the esophagus and stomach when taken by mouth. Berberine used intravenously (through the veins) may cause abnormal heart rhythms. Based on laboratory and animal studies, berberine may increase blood concentrations of bilirubin. Berberine theoretically may cause low blood pressure, although a different chemical in goldenseal, hydrastine, may actually cause increased blood pressure. There is limited study of the blood pressure effects of these agents in humans. Based on laboratory and animal studies, the use of goldenseal or berberine could increase the risk of bleeding. However, there are no reliable published reports of bleeding in humans. Caution is advised in patients with bleeding disorders or taking drugs that may increase the risk of bleeding. Dosing adjustments may be necessary. Based on an initial report, goldenseal or berberine may cause increased sun sensitivity, although this is not a commonly reported symptom. Based on laboratory studies, berberine may lower blood sugar. Caution is advised in patients with diabetes or hypoglycemia, and in those taking drugs, herbs, or supplements that affect blood sugar. Serum glucose levels may need to be monitored by a healthcare provider, and medication adjustments may be necessary. "

"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 for cancer prevention: global perspective. Garland CF, Gorham ED, Mohr SB, Garland FC. Ann Epidemiol. 2009 Jul;19(7):468-83. Review. PMID: 19523595