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Developmental toxicity evaluation of berberine in rats and mice. Jahnke GD, Price CJ, Marr MC, Myers CB, George JD. Birth Defects Res B Dev Reprod Toxicol. 2006 Jun;77(3):195-206. PMID: 16634078 DOI: 10.1002/bdrb.20075 BACKGROUND: Berberine, a plant alkaloid, is found in some herbal teas and health-related products. It is a component of goldenseal, an herbal supplement. Berberine chloride dihydrate (BCD) was evaluated for developmental toxicity in rats and mice. METHODS: Berberine chloride dihydrate was administered in the feed to timed-mated Sprague-Dawley (CD) rats (0, 3625, 7250, or 14,500 ppm; on gestational days [GD] 6-20), and Swiss Albino (CD-1) mice (0, 3500, 5250, or 7000 ppm; on GD 6-17). Ingested doses were 0, 282, 531, and 1313 mg/kg/day (rats) and 0, 569, 841, and 1155 mg/kg/day (mice). RESULTS:There were no maternal deaths. The rat maternal lowest observed adverse effect level (LOAEL), based on reduced maternal weight gain, was 7250 ppm. The rat developmental toxicity LOAEL, based on reduced fetal body weight per litter, was 14,500 ppm. In the mouse study, equivocal maternal and developmental toxicity LOAELs were 5250 ppm. Due to scattering of feed in the high dose groups, a gavage study at 1000 mg/kg/day was conducted in both species. CONCLUSIONS: In rats, maternal, but not fetal adverse effects were noted. The maternal toxicity LOAEL remained at 7250 ppm (531 mg/kg/day) based on the feed study and the developmental toxicity NOAEL was raised to 1000 mg/kg/day BCD based on the gavage study. In the mouse, 33% of the treated females died. Surviving animals had increased relative water intake, and average fetal body weight per litter decreased 5-6% with no change in live litter size. The maternal toxicity LOAEL remained at 5250 ppm (841 mg/kg/day) BCD, based on increased water consumption. The developmental toxicity LOAEL was raised to 1000 mg/kg/day BCD based on decreased fetal body weight.

Coconut kernel protein modifies the effect of coconut oil on serum lipids. Padmakumaran Nair KG, Rajamohan T, Kurup PA. Plant Foods Hum Nutr. 1999;53(2):133-44. PMID: 10472790 DOI: 10.1023/A:1008078103299 Feeding coconut kernel along with coconut oil in human volunteers has been found to reduce serum total and LDL cholesterol when compared to feeding coconut oil alone. This effect of the kernel was also observed in rats. Since many plant proteins have been reported to exert a cholesterol lowering effect, a study was carried out on the effect of isolated kernel protein in rats. Feeding kernel protein resulted in lower levels of cholesterol, phospholipids and triglycerides in the serum and most tissues when compared to casein fed animals. Rats fed kernel protein had (1) increased hepatic degradation of cholesterol to bile acids, (2) increased hepatic cholesterol biosynthesis, and (3) decreased esterification of free cholesterol. In the intestine, however, cholesterogenesis was decreased. The kernel protein also caused decreased lipogenesis in the liver and intestine. This beneficial effect of the kernel protein is attributed to its very low lysine/arginine ratio 2.13% lysine and 24.5% arginine....

Berberine reduces the hypoxic-ischemic insult in rat pup brain. Benaissa F, Mohseni-Rad H, Rahimi-Moghaddam P, Mahmoudian M. Acta Physiol Hung. 2009 Jun;96(2):213-20. PMID: 19457765 DOI: 10.1556/APhysiol.96.2009.2.6 Pathologic review of the samples obtained from rats treated with different doses of berberine in comparison with samples from pups treated by normal saline showed that there was a significant reduction of brain injury and edema in the rats treated with berberine. Our study also demonstrates that berberine reduces brain ischemic-hypoxic injury dose-dependently. Therefore, beberine may be considered as useful anti-stroke agent.

Prevention of skeletal muscle insulin resistance by dietary cod protein in high fat-fed rats. Lavigne C, Tremblay F, Asselin G, Jacques H, Marette A. Am J Physiol Endocrinol Metab. 2001 Jul;281(1):E62-71. PMID: 11404223 These data demonstrate that feeding cod protein prevents obesity-induced muscle insulin resistance in high fat-fed obese rats at least in part through a direct action of amino acids on insulin-stimulated glucose uptake in skeletal muscle cells.

Harauma A, Moriguchi T. Aged garlic extract improves blood pressure in spontaneously hypertensive rats more safely than raw garlic. J Nutr. 2006 Mar;136(3 Suppl):769S-773S. PMID: 16484560 [PubMed - indexed for MEDLINE]

Phytase activity in the human and rat small intestine. Iqbal TH, Lewis KO, Cooper BT. Gut. 1994 Sep;35(9):1233-6. PMID: 7959229

Regression of warfarin-induced medial elastocalcinosis by high intake of vitamin K in rats. Schurgers LJ, Spronk HM, Soute BA, Schiffers PM, DeMey JG, Vermeer C. Blood. 2007 Apr 1;109(7):2823-31. PMID: 17138823 DOI 10.1182/blood-2006-07-035345. This is the first study in rats demonstrating that AC and the resulting decreased arterial distensibility are reversible by high-VK intake

Egg yolk proteins suppress azoxymethane-induced aberrant crypt foci formation and cell proliferation in the colon of rats. Ishikawa S, Asano T, Takenoshita S, Nozawa Y, Arihara K, Itoh M. Nutr Res. 2009 Jan;29(1):64-9. PMID: 19185779 These results indicate that dietary egg yolk proteins have a preventive effect on AOM-induced large bowel carcinogenesis in rats; it exerts this effect by altering cell proliferation through SCFA production. This study suggests that the consumption of egg yolk proteins might be protective against colon carcinogenesis.

[Action of soluble carbohydrates from avocado (Persea gratissima Gaertner) fruit on utilization of calcium in the rat] Raonimalala AF, Digaud A, Fournier P. Ann Nutr Aliment. 1980;34(4):735-44. French. PMID: 7224495

Dietary omega-3 polyunsaturated fatty acids promote colon carcinoma metastasis in rat liver. Griffini P, Fehres O, Klieverik L, Vogels IM, Tigchelaar W, Smorenburg SM, Van Noorden CJ. Cancer Res. 1998 Aug 1;58(15):3312-9. PMID: 9699661

Inositols prevent and reverse endothelial dysfunction in diabetic rat and rabbit vasculature metabolically and by scavenging superoxide. Nascimento NR, Lessa LM, Kerntopf MR, Sousa CM, Alves RS, Queiroz MG, Price J, Heimark DB, Larner J, Du X, Brownlee M, Gow A, Davis C, Fonteles MC. Proc Natl Acad Sci U S A. 2006 Jan 3;103(1):218-23. Epub 2005 Dec 22. PMID: 16373499 doi: 10.1073/pnas.0509779103

I'm always on the lookout for foods rich in vitamin K2 MK-4, because it's so important and so rare in the modern food system. I heard some internet rumors that marrow might be rich in fat-soluble vitamins. Google let me down, so I decided to look through the rat studies on K2 MK-4 in which they looked at its tissue distribution. I found one that looked at the K2 MK-4 content in different tissues of rats fed vitamin K1. Marrow was rich in K2, along with testes. It contains 10-20 times more MK-4 than liver by weight, and more than any of the other organs they tested (serum, liver, spleen, kidney, heart, testes, marrow, brain) except testes. They didn't include values for salivary gland and pancreas, the two richest sources.

Mice injected with cancer cells experienced significantly elevated levels of C-reactive protein, white blood cells, and lipid peroxidation compared with control mice. These levels were reduced in animals that received cisplatin and/or DHA. While treatment with 125 mg/kg DHA inhibited tumor growth by 38 percent compared to untreated animals, 250 mg/kg suppressed tumor growth by 79 percent, which was a greater effect than that of cisplatin alone (which was associated with a 55 percent reduction). The combination of DHA and cisplatin resulted in an 81 percent inhibition of growth, while reducing elevated white blood cell levels (leukocytosis) to normal levels. Treatment with the higher dose of DHA alone was associated with a similar reduction in white blood cells, which, when elevated, are associated with tumor growth. A strong relationship was observed between tumor growth and white blood cell levels as well as C-reactive protein levels. In another experiment with rats treated with cisplatin, the addition of 250 mg/kg DHA prevented lethal kidney toxicity in 88 percent of the animals that received it, while none of the rats that received cisplatin alone survived.

Improved cholecalciferol nutrition in rats is noncalcemic, suppresses parathyroid hormone and increases responsiveness to 1, 25-dihydroxycholecalciferol. Vieth R, Milojevic S, Peltekova V. J Nutr. 2000 Mar;130(3):578-84. PMID: 10702588 We conclude suppression of 1,25(OH)(2)D and PTH, and higher renal VDR mRNA and 24-hydroxylase did not involve higher free 1,25(OH)(2)D concentration or a first pass effect at the gut. Thus, 25(OH)D or a metabolite other than 1,25(OH)(2)D is a physiological, transcriptionally and biochemically active, noncalcemic vitamin D metabolite. When viewed from a perspective that starts with higher vitamin D nutrition, the results indicate that low vitamin D nutrition may bring about a form of resistance to 1,25(OH)2D. This situation would explain why, in humans, nutritional rickets and osteomalacia are commonly associated with normal or increased levels of 1,25(OH)2D (Chesney et al. 1981Citation , Eastwood et al. 1979Citation , Garabedian et al. 1983Citation ,Rasmussen et al. 1980Citation )-these are not like the low hormone levels associated with any other endocrine-deficiency disorder. A connection between lower vitamin D nutrition and vitamin D resistance helps to explain why the supposedly inactive compound 25(OH)D is more relevant in diagnosing nutritional rickets than is the active hormone 1,25(OH)2D. If the features of improved vitamin D nutrition shown here were demonstrated for any newly synthesized compound, the compound would be classified as a noncalcemic 1,25(OH)2D analogue (Brown et al. 1989Citation , Finch et al. 1999Citation , Goff et al. 1993Citation , Koshizuka et al. 1999Citation ). Thus, we contend that 25(OH)D or a metabolite of it other than 1,25(OH)2D exists as a physiological and biologically-active noncalcemic vitamin D metabolite whose effects require further examination, particularly in relationship to studies involving the synthetic analogs of 1,25(OH)2D.

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

Progression of diethylnitrosamine-induced hepatic carcinogenesis in carnitine-depleted rats. Al-Rejaie SS, Aleisa AM, Al-Yahya AA, Bakheet SA, Alsheikh A, Fatani AG, Al-Shabanah OA, Sayed-Ahmed MM. World J Gastroenterol. 2009 Mar 21;15(11):1373-80. PMID: 19294768

Oral administration of both tetrahydrobiopterin and L-arginine prevents endothelial dysfunction in rats with chronic renal failure. Yamamizu K, Shinozaki K, Ayajiki K, Gemba M, Okamura T. J Cardiovasc Pharmacol. 2007 Mar;49(3):131-9. PMID: 17414224 doi: 10.1097/FJC.0b013e31802f9923

Alteration of natural killer cell-mediated cytotoxicity in rats treated with selenium, diethylnitrosamine and ethylnitrosourea. Talcott PA, Exon JH, Koller LD. Cancer Lett. 1984 Jul;23(3):313-22. PMID: 6611196

Dietary long-chain (n-3) fatty acids facilitate immune cell activation in sedentary, but not exercise-trained rats. Robinson LE, Field CJ. J Nutr. 1998 Mar;128(3):498-504. PMID: 9482755

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.