Group items tagged

Benfotiamine, a synthetic S-acyl thiamine derivative, has different mechanisms of action and a different pharmacological profile than lipid-soluble thiamine disulfide derivatives. Volvert ML, Seyen S, Piette M, Evrard B, Gangolf M, Plumier JC, Bettendorff L. BMC Pharmacol. 2008 Jun 12;8:10. PMID: 18549472 doi:10.1186/1471-2210-8-10 Conclusion Our results show that, though benfotiamine strongly increases thiamine levels in blood and liver, it has no significant effect in the brain. This would explain why beneficial effects of benfotiamine have only been observed in peripheral tissues, while sulbutiamine, a lipid-soluble thiamine disulfide derivative, that increases thiamine derivatives in the brain as well as in cultured cells, acts as a central nervous system drug. We propose that benfotiamine only penetrates the cells after dephosphorylation by intestinal alkaline phosphatases. It then enters the bloodstream as S-benzoylthiamine that is converted to thiamine in erythrocytes and in the liver. Benfotiamine, an S-acyl derivative practically insoluble in organic solvents, should therefore be differentiated from truly lipid-soluble thiamine disulfide derivatives (allithiamine and the synthetic sulbutiamine and fursultiamine) with a different mechanism of absorption and different pharmacological properties.

The Diet-Heart Hypothesis: Subdividing Lipoproteins Two posts ago, we made the rounds of the commonly measured blood lipids (total cholesterol, LDL, HDL, triglycerides) and how they associate with cardiac risk. It's important to keep in mind that many things associate with cardiac risk, not just blood lipids. For example, men with low serum vitamin D are at a 2.4-fold greater risk of heart attack than men with higher D levels. That alone is roughly equivalent to the predictive power of the blood lipids you get measured at the doctor's office. Coronary calcium scans (a measure of blood vessel calcification) also associate with cardiac risk better than the most commonly measured blood lipids. Lipoproteins Can be Subdivided into Several Subcategories In the continual search for better measures of cardiac risk, researchers in the 1980s decided to break down lipoprotein particles into sub-categories. One of these researchers is Dr. Ronald M. Krauss. Krauss published extensively on the association between lipoprotein size and cardiac risk, eventually concluding (source): The plasma lipoprotein profile accompanying a preponderance of small, dense LDL particles (specifically LDL-III) is associated with up to a threefold increase in the susceptibility of developing [coronary artery disease]. This has been demonstrated in case-control studies of myocardial infarction and angiographically documented coronary disease. Krauss found that small, dense LDL (sdLDL) doesn't travel alone: it typically comes along with low HDL and high triglycerides*. He called this combination of factors "lipoprotein pattern B"; its opposite is "lipoprotein pattern A": large, buoyant LDL, high HDL and low triglycerides. Incidentally, low HDL and high triglycerides are hallmarks of the metabolic syndrome, the quintessential modern metabolic disorder. Krauss and his colleagues went on to hypothesize that sdLDL promotes atherosclerosis because of its ability to penetrate the artery wall more easily

Effects of dairy products naturally enriched with cis-9,trans-11 conjugated linoleic acid on the blood lipid profile in healthy middle-aged men. Tricon S, Burdge GC, Jones EL, Russell JJ, El-Khazen S, Moretti E, Hall WL, Gerry AB, Leake DS, Grimble RF, Williams CM, Calder PC, Yaqoob P. Am J Clin Nutr. 2006 Apr;83(4):744-53. PMID: 16600923 CONCLUSION: Dairy products naturally enriched with cis-9,trans-11 CLA and trans-11 18:1 do not appear to have a significant effect on the blood lipid profile

Opposing effects of cis-9,trans-11 and trans-10,cis-12 conjugated linoleic acid on blood lipids in healthy humans. Tricon S, Burdge GC, Kew S, Banerjee T, Russell JJ, Jones EL, Grimble RF, Williams CM, Yaqoob P, Calder PC. Am J Clin Nutr. 2004 Sep;80(3):614-20. PMID: 15321800 Conclusion: Divergent effects of cis-9,trans-11 CLA and trans-10,cis-12 CLA appear on the blood lipid profile in healthy humans: trans-10,cis-12 CLA increases LDL:HDL cholesterol and total:HDL cholesterol, whereas cis-9,trans-11 CLA decreases them.

The effects of conjugated linoleic acid on human health-related outcomes. Tricon S, Burdge GC, Williams CM, Calder PC, Yaqoob P. Proc Nutr Soc. 2005 May;64(2):171-82. Review. PMID: 15960862 Conjugated linoleic acid (CLA) is a collective term for a mixture of positional and geometric isomers of conjugated dienoic derivatives of linoleic acid. CLA has received considerable attention as a result of animal experiments that report anti-carcinogenic, anti-atherogenic and anti-diabetic properties, and modulation of body composition and immune function. Several studies of CLA supplementation in human subjects have now been published, but in contrast to animal studies there has been marked variation between reports on the health-related outcomes. The consensus from seventeen published studies in human subjects is that CLA does not affect body weight or body composition. Some detrimental effects of the trans-10,cis-12 CLA isomer have also been reported in terms of altered blood lipid composition and impaired insulin sensitivity. Finally, CLA has only limited effects on immune functions in man. However, there have been reports of some interesting isomer-specific effects of CLA on the blood lipid profile, but not on immune function. These isomer-specific effects need further investigation. Until more is known, CLA supplementation in man should be considered with caution.

Fernandez ML, West KL. Mechanisms by which dietary fatty acids modulate plasma lipids. J Nutr. 2005 Sep;135(9):2075-8. Review. PMID: 16140878 [PubMed - indexed for MEDLINE]

Turner B, Molgaard C, Marckmann P. Effect of garlic (Allium sativum) powder tablets on serum lipids, blood pressure and arterial stiffness in normo-lipidaemic volunteers: a randomised, double-blind, placebo-controlled trial. Br J Nutr. 2004 Oct;92(4):70

"Coconut oil is extracted from the kernel or meat of matured coconut harvested from the coconut palm (Cocos nucifera). Throughout the tropical world it has provided the primary source of fat in the diets of millions of people for generations. It has various applications in food, medicine, and industry. What makes coconut oil different from most other dietary oils is the basic building blocks or fatty acids making up the oil. Coconut oil is composed predominately of a special group of fat molecules known as medium chain fatty acids (MCFA). The majority of fats in the human diet are composed almost entirely of long chain fatty acids (LCFA). The primary difference between MCFA and LCFA is the size of the molecule, or more precisely, the length of the carbon chain that makes up the backbone of the fatty acid. MCFA have a chain length of 6 to 12 carbons. LCFA contain 14 or more carbon Historically, many populations within the tropics have used coconut medicinally as a treatment for a wide variety of ailments.[8] A study into the effects of a "diet rich in.." medium-chain fatty acids (such as in coconut oil and butter) concluded that "MCFAs in the form of MCTs significantly increased plasma triacylglycerol and LDL-cholesterol concentrations and the ratio of LDL to HDL cholesterol and thereby resulted in a less beneficial lipid profile overall."[9] Further, research done by nutritionist Mary Enig has found that non-hydrogenated coconut oil (i.e. extra-virgin) consumed in moderate amounts "is at worst neutral with respect to atherogenicity of fats and oils and, in fact, is likely to be a beneficial oil for prevention and treatment of some heart disease."[10] The lack of negative effects of a diet rich in coconut oil on cardiovascular health is born out in studies of Polynesian populations who consume as much as 65% of their calories in the form of coconut oil and yet, have almost no incidence of heart disease and normal blood lipid profiles.[11]

Blood pressure and atherogenic lipoprotein profiles of fish-diet and vegetarian villagers in Tanzania: the Lugalawa study. Pauletto P, Puato M, Caroli MG, Casiglia E, Munhambo AE, Cazzolato G, Bittolo Bon G, Angeli MT, Galli C, Pessina AC. Lancet. 1996 Sep 21;348(9030):784-8. PMID: 8813985 Interpretation In these villagers, consumption of freshwater fish (300-600 g daily) was associated with raised plasma concentrations of n-3 polyunsaturated fatty acids, lower blood pressure, and lower plasma lipid concentrations. In conclusion, our findings confirm that the favourable risk factor profile originally described for Eskimos living on a diet rich in n-3 polyunsaturated fatty acids is real, and not overestimated.

The effect of ingestion of egg on the serum lipid profile of healthy young Indians. Chakrabarty G, Manjunatha S, Bijlani RL, Ray RB, Mahapatra SC, Mehta N, Lakshmy R, Vashisht S, Manchanda SC. Indian J Physiol Pharmacol. 2004 Jul;48(3):286-92. PMID: 15648400

Metabolic and physiologic improvements from consuming a paleolithic, hunter-gatherer type diet. Frassetto LA, Schloetter M, Mietus-Synder M, Morris RC Jr, Sebastian A. Eur J Clin Nutr. 2009 Aug;63(8):947-55. Epub 2009 Feb 11. PMID: 19209185 doi:10.1038/ejcn.2009.4 Conclusions: Even short-term consumption of a paleolithic type diet improves BP and glucose tolerance, decreases insulin secretion, increases insulin sensitivity and improves lipid profiles without weight loss in healthy sedentary humans.

"High serum selenium associated with elevated LDL and total cholesterol By Helen Albert 21 January 2010 Atherosclerosis 2009; Advance online publication MedWire News: High levels of serum selenium are associated with elevated total and low-density lipoprotein (LDL) cholesterol, report US researchers. The results add weight to those of a previous UK study, reported by MedWire News, that reported an association between high plasma selenium and an adverse lipid profile. Eliseo Guallar (Johns Hopkins University Bloomberg School of Public Health, Baltimore, Maryland) and colleagues carried out a cross-sectional analysis of 1159 individuals aged 56.8 years on average who participated in the National Health and Nutrition Examination Survey (NHANES) 2003-2004."

The results suggest that a short-term ketogenic diet does not have a deleterious effect on CVD risk profile and may improve the lipid disorders characteristic of atherogenic dyslipidemia. A ketogenic diet favorably affects serum biomarkers for cardiovascular disease in normal-weight men. Sharman MJ, Kraemer WJ, Love DM, Avery NG, Gómez AL, Scheett TP, Volek JS. J Nutr. 2002 Jul;132(7):1879-85. PMID: 12097663

Metabolic effects of conjugated linoleic acid in humans: the Swedish experience. Riserus U, Smedman A, Basu S, Vessby B. Am J Clin Nutr. 2004 Jun;79(6 Suppl):1146S-1148S. PMID: 15159248 CONCLUSIONS CLA and specifically the isolated isomers are interesting model fatty acids for studies of the effects of (structural differences of) unsaturated fatty acids in humans. Today, there is no clear indication for human use of CLA concentrates. The possible importance of the small reduction of body fat after supplementation with the commercially available CLA products, without evidence of an associated improvement in the metabolic profile, has to be weighed against the apparent reduction of HDL cholesterol and an increased lipid peroxidation. The possible health consequences of prolonged treatment periods are at present unknown. Human supplementation with high doses of the trans-10,cis-12 CLA isomer should be avoided while awaiting further information on possible effects and side effects. However, it cannot be excluded that future studies could point to clinical applications, eg, as a result of antitumorigenic properties or as a tool to prevent weight gain. This possibility certainly requires more research to increase the understanding of the mechanisms behind the effects of CLA and specific CLA isomers on a molecular level. More controlled studies in defined populations are needed, as are controlled studies for comparisons of the effects of different and well-defined (mixtures of) isomers and human studies of longer duration to secure long-term effects and safety.

Berberine is a novel cholesterol-lowering drug working through a unique mechanism distinct from statins. Kong W, Wei J, Abidi P, Lin M, Inaba S, Li C, Wang Y, Wang Z, Si S, Pan H, Wang S, Wu J, Wang Y, Li Z, Liu J, Jiang JD. Nat Med. 2004 Dec;10(12):1344-51. Epub 2004 Nov 7. PMID: 15531889 doi:10.1038/nm1135 We identify berberine (BBR), a compound isolated from a Chinese herb, as a new cholesterol-lowering drug. Oral administration of BBR in 32 hypercholesterolemic patients for 3 months reduced serum cholesterol by 29%, triglycerides by 35% and LDL-cholesterol by 25%. Treatment of hyperlipidemic hamsters with BBR reduced serum cholesterol by 40% and LDL-cholesterol by 42%, with a 3.5-fold increase in hepatic LDLR mRNA and a 2.6-fold increase in hepatic LDLR protein. Using human hepatoma cells, we show that BBR upregulates LDLR expression independent of sterol regulatory element binding proteins, but dependent on ERK activation. BBR elevates LDLR expression through a post-transcriptional mechanism that stabilizes the mRNA. Using a heterologous system with luciferase as a reporter, we further identify the 5' proximal section of the LDLR mRNA 3' untranslated region responsible for the regulatory effect of BBR. These findings show BBR as a new hypolipidemic drug with a mechanism of action different from that of statin drugs.