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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.

Acid-base balance has an effect on bone turnover, especially on the rates of bone resorption and calcium mobilization. Bone mineral participates in the defense against acid-base disturbances, especially against metabolic acidosis (Lemann et al. 1966, Green & Kleeman 1991). The role of the bone mineral is important in the acid-base disorders, as no appreciable change in the intestinal calcium absorption occurs (Bichara et al. 1990). In the mammalian body, mainly three hormones regulate the calcium metabolism and the bone turnover. 1,25-dihydroxycholecalciferol (vitamin D derivative) increases calcium absorption from the intestine and, indirectly, from bone. Parathyroid hormone mobilizes calcium from the bone and increases the urinary phosphate excretion. Calcitonin inhibits bone resorption (Ganong 1981). Used as drugs, these hormones are also capable of inducing acid-base disorders. Calcitonin administration (Escanero et al. 1991) and vitamin D excess (Bichara et al. 1990) have been reported to cause metabolic alkalosis.

Food table The table allows the assessment of dietary effects on acid-base balance. Foodstuffs with a negative value (milliequivalents per 100 g) exert a base (B) effect, foodstuffs with a positive value an acid (A) effect. Neutral foodstuffs are label

"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. "

Symposium 2000 Acid-Base Metabolism European Journal of Nutrition 40 (2001)

Conclusion A low-carbohydrate plant-based diet has lipid-lowering advantages over a high-carbohydrate, low-fat weight-loss diet in improving heart disease risk factors not seen with conventional low-fat diets with animal products. The Effect of a Plant-Based Low-Carbohydrate ("Eco-Atkins") Diet on Body Weight and Blood Lipid Concentrations in Hyperlipidemic Subjects David J. A. Jenkins; Julia M. W. Wong; Cyril W. C. Kendall; Amin Esfahani; Vivian W. Y. Ng; Tracy C. K. Leong; Dorothea A. Faulkner; Ed Vidgen; Kathryn A. Greaves; Gregory Paul; William Singer Arch Intern Med. 2009;169(11):1046-1054. DOI: 10.1001/archinternmed.2009.115

Urine pH is an indicator of dietary acid-base load, fruit and vegetables and meat intakes: results from the European Prospective Investigation into Cancer and Nutrition (EPIC)-Norfolk population study. Welch AA, Mulligan A, Bingham SA, Khaw KT. Br J Nutr. 2008 Jun;99(6):1335-43. Epub 2007 Nov 28. PMID: 18042305 In conclusion, a more alkaline diet, higher fruit and vegetable and lower meat intake were related to more alkaline urine with a magnitude similar to intervention studies. As urine pH relates to dietary acid-base load its use to monitor change in consumption of fruit and vegetables, in individuals, warrants further investigation.

The importance of calcium, potassium, and acid-base homeostasis in bone health and osteoporosis prevention. Tylavsky FA, Spence LA, Harkness L. J Nutr. 2008 Jan;138(1):164S-165S. PMID: 18156418 In concert with the acid-base literature, protein intake is considered to be a net acid-producing substance and thus a net negative risk factor for bone dissolution. However, substantial literature supports the beneficial effects on skeletal metabolism when higher protein levels are consumed in concert with adequate calcium, potassium, and other minerals, regardless of the source of protein (24-26). The Dietary Approaches to Stopping Hypertension (DASH) diet (27) is a calcium-rich diet that emphasizes fruits, vegetables, and low-fat dairy products. This diet underscores the importance of consuming a complement of foods from meats, grains, dairy, fruits, and vegetables as prudent for promoting optimal bone health. In the following articles, Rafferty and Lanham-New carefully review the evidence on the interaction of specific diet components that impact bone health and conclude that a balanced diet with recommended servings of dairy products and a variety of fruits and vegetables is prudent for optimal bone health. Additionally, they comment on future research directions for consideration by the scientific community.

The acid-base hypothesis: diet and bone in the Framingham Osteoporosis Study. Tucker KL, Hannan MT, Kiel DP. Eur J Nutr. 2001 Oct;40(5):231-7. PMID: 11842948 RESULTS: As hypothesized, magnesium, potassium, fruit and vegetable intakes were significantly associated with bone mineral density at baseline and among men, with lower bone loss over four years. In contrast to the hypothesis, higher rather than lower protein intakes were associated with lower bone loss. CONCLUSION: Together these results support the role of base forming foods and nutrients in bone maintenance. The role of protein appears to be complex and is probably dependent on the presence of other nutrients available in a mixed diet. A balanced diet with ample fruit and vegetables and adequate protein appears to be important to bone mineral density.

The table lists the acid, base values for 114 common foods. Base-producing foods are fruits and vegetables, whereas grains, meats, fish, cheese and salted processed foods are acid-producing.

"NEW YORK (Reuters Health) - Women who eat greater amounts of plant-based foods and drinks with the naturally occurring flavonoid, apigenin, may have a decreased risk for ovarian cancer, study findings suggest. Apigenin, found in celery, parsley, red wine, tomato sauce, and other plant-based foods may be "particularly beneficial," said Dr. Margaret A. Gates, of Brigham and Women's Hospital and Harvard Medical School, in Boston, Massachusetts. Flavanoids are compounds with antioxidant properties that protect cells against damage by oxygen molecules. In a study that compared flavonoid intake among women with and without ovarian cancer, women reporting the highest apigenin intake had a "borderline significant decrease" in ovarian cancer risk over women reporting the lowest apigenin intake, Gates and her associates report in the International Journal of Cancer."

Diet, evolution and aging--the pathophysiologic effects of the post-agricultural inversion of the potassium-to-sodium and base-to-chloride ratios in the human diet. Frassetto L, Morris RC Jr, Sellmeyer DE, Todd K, Sebastian A. Eur J Nutr. 2001 Oct;40(5):200-13. Review. PMID: 11842945

2nd International Acid-Base Symposium Nutrition - Health - Disease Munich, Germany, September 8 - 9, 2006

Welch AA, Bingham SA, Reeve J, Khaw KT. More acidic dietary acid-base load is associated with reduced calcaneal broadband ultrasound attenuation in women but not in men: results from the EPIC-Norfolk cohort study. Am J Clin Nutr. 2007 Apr;85(4):1134-41.

The most common imbalance in the acid-base balance in the industrialized countries is mild chronic metabolic acidosis caused by the diet rich in the animal protein. Proteins are metabolized to organic acids. The typical American diet produces after metabolism approximately 100 meq of acid every day (Barzel 1995). This kind of a diet has been proved to cause aciduria and calciuria as a consequence of acidosis and thus a loss of total calcium of the body (Breslau et al. 1988, Schuette et al. 1980, Licata et al. 1981). Cola drinks that contain phosphoric acid are another acidosis-inducing ingredient of diet, especially among young people (Barzel 1995).

Low vitamin D serum level is related to severe fibrosis and low responsiveness to IFN-based therapy in genotype 1 chronic hepatitis C Salvatore Petta et al. Hepatology, Volume 9999 Issue 999A, Page NA. Published Online: 4 Dec 2009 DOI: 10.1002/hep.23489 Conclusions: G1 CHC patients had low 25(OH)D serum levels, possibly due to reduced CYP27A1 expression. Low vitamin D is linked to severe fibrosis and low SVR on IFN-based therapy. (HEPATOLOGY 2010.)

"Lisa is one of early success stories: a heart scan score of 447 in her early 40's, modest reduction of CT heart scan score three years ago. However, Lisa had a difficult time locating oil-based vitamin D. There has, in fact, been a national run on vitamin D and I'm told that even manufacturers are scrambling to keep up with the booming demand. So, she bought tablets instead and was taking 3000 units per day. She came in for a routine check. Lisa's 25-OH-vitamin D3: 17 ng/ml, signifying severe deficiency, the same as if she were taking nothing at all. (Recall that we aim for 50 ng/ml.) In other words, vitamin D tablets do not work. It is shameful. I see numerous women taking calcium tablets with D--the vitamin D does not work. I've actually seen blood levels of zero on these preparations. "