In the post Diabetes Part I: Biology and molecular dynamics of diabetes, I described a pathological biomolecular process through which diabetes arises from obesity or metabolic syndrome. I also provided reference links to publications amplifying on the details of the process, including some 2010 findings.
The context of the following discussion is that of the CDC and many other respectable organizations – Type 2 diabetes is preventable and controllable(ref).
Control of diabetes via drugs is a mainline approach in our society. Much speculation has appeared recently in the popular news regarding the safety of the diabetes drug Avandia (rosiglitazone) and whether the FDA will continue to allow it to stay on the market. Avandia appears to significantly increase fluid retention and the probability of heart attacks and heart disease, but this week a panel of experts convened by the FDA voted to recommend keeping the drug on the market. “Only 12 of the 33 members voted to withdraw Avandia, while an additional 10 voted to allow the drug to be prescribed only with severe limitations such as requiring physicians and patients to be educated about its risks. The panel, like the FDA itself, was largely divided over what to make of Avandia’s potential health risks(ref).” The commercial stakes are enormous since the market for non-insulin oral diabetes drugs is estimated to be $8.4 billion dollars(ref).
In the March 2010 blog post Recent diabetes-related clinical trials , I reviewed five recent clinical trials related to diabetes treatments, three that have failed and two that have succeeded. I concluded by commenting on what I thought were some important underlying messages, including:
· The clinical trial failures indicate how much we still are in an extremely expensive trial-and-error approach to treating diabetes, as I believe is the case for multiple other diseases.
· All the treatments that were the subjects of the trials related to management of diabetic conditions or cardiovascular risk factors. Such management is extremely important but lifestyle and dietary factors can be equally or even more important in preventing onset of diabetes as well as its management.
This last point is what this current blog entry is about. While drugs may be important for control of diabetes for some patients, this blog post looks in a different direction – to lifestyle, dietary and food supplement interventions. In this post, I will characterize how certain of the lifestyle, dietary habits and supplements in the anti-aging firewalls regimens work on a molecular level to disrupt the diabetes process. These lifestyle and dietary factors are extremely relevant.
“A number of lifestyle factors are known to be important to the development of type 2 diabetes. In one study, those who had high levels of physical activity, a healthy diet, did not smoke, and consumed alcohol in moderation had an 82% lower rate of diabetes. When a normal weight was included the rate was 89% lower. In this study a healthy diet was defined as one high in fiber, with a high polyunsaturated to saturated fat ratio, and a lower mean glycemic index(ref). Obesity has been found to contribute to approximately 55% type 2 diabetes(ref), and decreasing consumption of saturated fats and trans fatty acids while replacing them with unsaturated fats may decrease the risk(ref). The increased rate of childhood obesity in between the 1960s and 2000s is believed to have led to the increase in type 2 diabetes in children and adolescents(ref).”
The Role of Exercise
It has long been known that, just as a sedentary lifestyle is a risk factor for Type 2 diabetes (ref)(ref), so is physical activity and exercise an important preventative activity. Back in 2002 the US Department of Health and Human Services published a position document Physical Activity Fundamental To Preventing Disease and the message of that document still stands. In that study, “vigorous physical activity is defined as exercise that made the respondent sweat and breathe hard for at least 20 minutes on 3 or more of the 7 days preceding the survey.”
How exercise works is described in very simple terms in the American Diabetes Association’s web page The Science of Exercise – Is physical activity the best medicine? “It’s free — Yes, it’s the crux of healthy living: exercise. And while just about everyone is better off working out regularly, exercise is, in some sense, the perfect drug for diabetes. Not only can it improve blood glucose control—which in itself reduces the risk of diabetes complications—but research suggests it may combat heart disease, weight gain, depression, and more. — Muscle contractions have a powerful effect on how the body processes glucose, the original biofuel. The muscles are the major consumer of glucose during exercise. It’s not surprising since they do most of the work. In each cell, muscles store dense packets of glucose, accounting for around 2,000 calories worth of energy throughout the body, according to Sheri Colberg-Ochs, PhD, a professor of exercise science at Old Dominion University in Norfolk, Va. “[This energy] just stays there unless you contract the muscle.” — During exercise, the muscles deplete their individual glucose reserves. To help restock their glucose supplies, the muscles change in two important ways: They become more sensitive to insulin—a hormone that escorts glucose from the bloodstream into body cells—and they also start to absorb glucose on their own, independently of insulin. — This second pathway created during exercise is a boon for anyone with type 2 diabetes, which is marked by insulin resistance. “When the body is at rest, it has one mechanism for getting glucose out of the bloodstream. That way is insulin,” says Colberg-Ochs. “What’s so good about exercise is that even if the muscles are insulin resistant at rest, that’s irrelevant with exercise.” — Exercise’s effect on glucose use occurs not just in people with type 2 but in almost everyone, including those with type 1 and pre-diabetes. A large study found that, in people with pre-diabetes, lifestyle changes that included 150 minutes a week of moderate-intensity exercise reduced the risk of progression to full-blown type 2 diabetes by 58 percent.”
Over the years there have been many studies and publications relating exercise to the control of diabetes. One of the latest is a July 2010 publication Is exercise a therapeutic tool for improvement of cardiovascular risk factors in adolescents with type 1 diabetes mellitus? A randomised controlled trial. “RESULTS: Exercise improved glycemic control by reducing HbA1c values in exercise groups (P=0.03, P=0.01 respectively) and no change in those who were not physically active (P=0.2). Higher levels of HbA1c were associated with higher levels of cholesterol, LDL-c, and triglycerides (P = 0.000 each). In both groups B and C , frequent exercise improved dyslipidemia and reduced insulin requirements significantly (P=0.00 both), as well as a reduction in BMI (P=0.05,P=0.00 respectively) and waist circumference(P=0.02, P=0.00 respectively). The frequency of hypoglycemic attacks were not statistically different between the control group and both intervention groups (4.7 +/- 3.56 and 4.82+/-4.23 ,P= 0.888 respectively ). Reduction of blood pressure was statistically insignificant apart from the diastolic blood presure in group C (P=0.04). CONCLUSION: Exercise is an indispensable component in the medical treatment of patients with T1DM as it improves glycemic control and decreases cardiovascular risk factors among them.”This theme of the importance of exercise is based on solid science as well as population studies and is reiterated in most serious articles on diabetes aimed at consumers and patients. “Physical activity is a key component of lifestyle change. In addition to helping a patient lose weight, exercise leads to a reduction in body fat, blood pressure and insulin resistance. Researchers report a one percent decrease in hemoglobin A1c levels (a marker of long-term glucose control) is associated with a 15 to 20 percent reduction in risk for cardiovascular complications and a 37 percent reduction in microvascular complications (like eye, kidney and nerve disease)(ref).”
Exercise! Personally, I strive for 45 minutes of exercise a day which could consist of mowing the lawn, brisk walking, swimming, treadmilling, yardwork or swimming.
Diet – foods to avoid
A number of publications stress the negative role in diabetes of consumption of saturated fats and trans fats. The 2003 publication Quality of dietary fatty acids, insulin sensitivity and type 2 diabetes reported “Epidemiological evidence and intervention studies clearly indicate that the quality of dietary fat influences insulin sensitivity in humans, in particular, saturated fat worsens it, while monounsaturated and omega-6 polyunsaturated fats improve it. Long chain omega-3 fatty acids do not seem to have any effect on insulin sensitivity, at least in humans. Moreover, there is also good epidemiological evidence that the quality of dietary fat may influence the risk of type 2 diabetes, again with saturated fat increasing and unsaturated fat decreasing this risk. No intervention study is available at the moment on this specific point, even if in the Finnish Diabetes Prevention Study the incidence of type 2 diabetes was reduced by a multifactorial intervention, which also included a reduction of saturated fat intake.”The evidence for this viewpoint continued to accumulate and the 2009 review publication Dietary fats and prevention of type 2 diabetes reported “Although type 2 diabetes is determined primarily by lifestyle and genes, dietary composition may affect both its development and complications. Dietary fat is of particular interest because fatty acids influence glucose metabolism by altering cell membrane function, enzyme activity, insulin signaling, and gene expression. This paper focuses on the prevention of type 2 diabetes and summarizes the epidemiologic literature on associations between types of dietary fat and diabetes risk. It also summarizes controlled feeding studies on the effects of dietary fats on metabolic mediators, such as insulin resistance. Taken together, the evidence suggests that replacing saturated fats and trans fatty acids with unsaturated (polyunsaturated and/or monounsaturated) fats has beneficial effects on insulin sensitivity and is likely to reduce risk of type 2 diabetes. Among polyunsaturated fats, linoleic acid from the n-6 series improves insulin sensitivity. On the other hand, long-chain n-3 fatty acids do not appear to improve insulin sensitivity or glucose metabolism. In dietary practice, foods rich in vegetable oils, including non-hydrogenated margarines, nuts, and seeds, should replace foods rich in saturated fats from meats and fat-rich dairy products. Consumption of partially hydrogenated fats should be minimized.”
A finer-tuning of this viewpoint can be found in the 2010 publication Session 4: CVD, diabetes and cancer: Diet, insulin resistance and diabetes: the right (pro)portions “Excess energy intake and positive energy balance are associated with the development of obesity and insulin resistance, which is a key feature underlying the pathophysiology of type 2 diabetes. It is possible that dietary macronutrient intake may also be important, in particular increased levels of sugar and fat. High-fat energy-dense diets contribute to energy excess and obesity. Fat type is also a factor, with evidence suggesting that saturated fat intake is linked to insulin resistance. However, controversy exists about the role of carbohydrate in the development of diabetes. Epidemiological studies suggest that the risk of diabetes is unrelated to the total amount of carbohydrate, but that fibre intake and glycaemic load are important. Common dietary advice for the prevention of diabetes often advocates complex carbohydrates and restriction of simple carbohydrates; however, sugars may not be the main contributor to glycaemic load. Evidence continues to emerge in relation to the influence of dietary sugars intake on insulin resistance. In broader dietary terms fruit and vegetable intake may influence insulin resistance, possibly related to increased intake of fibre and micronutrients or displacement of other food types. There is also considerable debate about the most effective diet and appropriate macronutrient composition to facilitate weight loss. Recent evidence suggests comparable effects of diets with varying macronutrient profiles on weight loss, which is predominantly related to energy restriction. However, based on the results of diabetes prevention trials focusing on lifestyle measures, evidence favours low-fat diets as the preferred approach for weight loss and diabetes prevention.”
Avoid saturated fats and trans-fats!
Foods with positive qualities with respect to diabetes
A number of foods with strong phytochemical content can counter the underlying processes of diabetes, a key message of the 2010 review paper Functional food targeting the regulation of obesity-induced inflammatory responses and pathologies. I can only discuss a few representative foods here as examples.
The blog entry Back to blueberries points out the role of pterostilbene, a key phytochemical in blueberries, in controlling tissue glycation and associated inflammation in diabetes. Pterostilbene is a stilbenoid chemically related to resveratrol. It is a powerful anti-inflammatory, responsible for some of the effects of blueberries in controlling a range of inflammatory disease conditions.
One of the theories of aging is Tissue Glycation, a process deeply implicated in diabetes. Tissue glycation involves cross linking of tissue proteins with sugars resulting in the formation of Advanced Glycation Endproducts (AGEs). The result of AGEs can be self-propagating systemic or “silent” tissue inflammation. AGEs are recognized by cell RAGE receptors which result in the production of cytokine chemicals that can induce unwanted and potentially deadly inflammation in blood vessels, nerve, liver and other tissues. Atherosclerosis can be a consequence. AGEs are responsible for much bodily mischief related to aging leading to deterioration of function and structure of organs. They play important roles in diabetes, atherosclerosis, vascular disease, kidney failure, and neuropathy including Alzheimer’s disease. The presence of AGEs also appears to negatively impact on immune system functioning. Diabetes in particular appears to have its roots due both to inflammation and to glycation. People with high blood sugar levels, diabetics and pre-diabetes are particularly susceptible to glycation.
I will quote only two of the publications relating blueberries to diabetes. The 2009 publication states Antiobesity and antidiabetic effects of biotransformed blueberry juice in KKAy mice reports “Biotransformation of blueberry juice by the Serratia vaccinii bacterium gave rise to adenosine monophosphate-activated protein kinase (AMPK) phosphorylation and glucose uptake in muscle cells and adipocytes, but inhibited adipogenesis. This study investigated the antiobesity and antidiabetic potential of biotransformed blueberry juice (BJ) in KKAy mice, rodent model of leptin resistance. — Incorporating BJ in drinking water protected young KKAy mice from hyperphagia and significantly reduced their weight gain. Moreover, BJ protected young KKAy mice against the development of glucose intolerance and diabetes mellitus. Chronic BJ administration in obese and diabetic KKAy mice reduced food intake and body weight. This effect could not fully explain the associated antidiabetic effect because BJ-treated mice still showed lower blood glucose level when compared with pair-fed controls. The adipokines pathway also seems to be involved because BJ significantly increased adiponectin levels in obese mice. — Conclusions: This study shows that BJ decreases hyperglycemia in diabetic mice, at least in part by reversing adiponectin levels. BJ also protects young pre-diabetic mice from developing obesity and diabetes. Thus, BJ may represent a novel complementary therapy and a source of novel therapeutic agents against diabetes mellitus.”
Another relevant publication is Dietary blueberry attenuates whole-body insulin resistance in high fat-fed mice by reducing adipocyte death and its inflammatory sequelae. “These results suggest that cytoprotective and antiinflammatory actions of dietary BB can provide metabolic benefits to combat obesity-associated pathology.”
Other colored berries
There are other papers describing anti-diabetic effects of blueberries and other colored berries such as Whole berries versus berry anthocyanins: interactions with dietary fat levels in the C57BL/6J mouse model of obesity and Inhibition of cancer cell proliferation and suppression of TNF-induced activation of NFkappaB by edible berry juice.
Eat strawberries, raspberries and other colored berries!
The blog entry Calorie restriction mimetics – focus on avocado extract points to a sugar in avocados, mannoheptulose, that is highly relevant for the control of diabetes. “Mannoheptulose is a hexokinase inhibitor. It is a heptose, a monosaccharide with seven carbon atoms. By blocking the enzyme hexokinase, it prevents glucose phosphorylation. As a result less dextrose units are broken down into smaller molecules in an organism. It is found as D-mannoheptulose in avocado(ref). ” In simple terms, it works to block the metabolism if glucose. “When fed to mice in fairly concentrated doses (roughly 300 milligrams per kilogram of an animal’s body weight), it improved insulin sensitivity and the clearance of glucose from the blood. Meaning it helped overcome diabetes-like impairments to blood-sugar control. MH supplementation also improved the ability of insulin, a hormone, to get cells throughout the body to do its bidding (and that’s a good thing). MH revved up the burning of fats in muscle(ref).”
The 2008 paper Inhibitory effect of naringenin chalcone on inflammatory changes in the interaction between adipocytes and macrophages has some very interesting things to say related to the diabetic process as described in the Diabetes Part 1 blog entry. For one thing, Naringenin Chalcone is not a Sicilian mobster; it is a phytochemical in tomatos. “Obese adipose tissue is characterized by an enhanced infiltration of macrophages. It is considered that the paracrine loop involving monocyte chemoattractant protein (MCP)-1 and tumor necrosis factor (TNF)-alpha between adipocytes and macrophages establishes a vicious cycle that augments the inflammatory changes and insulin resistance in obese adipose tissue. Polyphenols, which are widely distributed in fruit and vegetables, can act as antioxidants and some of them are also reported to have anti-inflammatory properties. Tomato is one of the most popular and extensively consumed vegetable crops worldwide, which also contains many flavonoids, mainly naringenin chalcone. We investigated the effect of flavonoids, including naringenin chalcone, on the production of proinflammatory mediators in lipopolysaccharide (LPS)-stimulated macrophages and in the interaction between adipocytes and macrophages. Naringenin chalcone inhibited the production of TNF-alpha, MCP-1, and nitric oxide (NO) by LPS-stimulated RAW 264 macrophages in a dose-dependent manner. Coculture of 3T3-L1 adipocytes and RAW 264 macrophages markedly enhanced the production of TNF-alpha, MCP-1, and NO compared with the control cultures; however, treatment with naringenin chalcone dose-dependently inhibited the production of these proinflammatory mediators. These results indicate that naringenin chalcone exhibits anti-inflammatory properties by inhibiting the production of proinflammatory cytokines in the interaction between adipocytes and macrophages. Naringenin chalcone may be useful for ameliorating the inflammatory changes in obese adipose tissue.” Of course tomatoes also contain lycopene and other healthful ingredients.
The 2008 paper Auraptene, a citrus fruit compound, regulates gene expression as a PPARalpha agonist in HepG2 hepatocytes indicates “Citrus fruit compounds have various activities that improve pathological conditions in many tissues. In this study, we examined the effect of auraptene contained mainly in the peel of citrus on peroxisome proliferator-activated receptor-alpha (PPARalpha) activation. — These results indicate that auraptene acts as a PPARalpha agonist in hepatocytes and that auraptene may improve lipid abnormality through PPARalpha activation in the liver.” The point is reinforced in the 2007 paper Citrus auraptene acts as an agonist for PPARs and enhances adiponectin production and MCP-1 reduction in 3T3-L1 adipocytes.
In other words, that strong pungent stuff in lemon and orange peels could be a good diabetes-fighter. Eat them!
Herbs and spices
For those of you who are hot pepper freaks and a bit overweight or concerned about diabetes, there is good news going back to the 1986 publication Capsaicin-induced beta-adrenergic action on energy metabolism in rats: influence of capsaicin on oxygen consumption, the respiratory quotient, and substrate utilization. The 2003 publication Capsaicin exhibits anti-inflammatory property by inhibiting IkB-a degradation in LPS-stimulated peritoneal macrophages casts light on how capsaicin works to control inflammation leading to diabetes. And so does the 2007 publication Capsaicin, a spicy component of hot peppers, modulates adipokine gene expression and protein release from obese-mouse adipose tissues and isolated adipocytes, and suppresses the inflammatory responses of adipose tissue macrophages. “Capsaicin inhibited the expressions of IL-6 and MCP-1 mRNAs and protein release from the adipose tissues and adipocytes of obese mice, whereas it enhanced the expression of the adiponectin gene and protein. The action of capsaicin is associated with NF-kappaB inactivation and/or PPARgamma activation. Moreover, capsaicin suppressed not only macrophage migration induced by the adipose tissue-conditioned medium, but also macrophage activation to release proinflammatory mediators.” These are exactly the actions needed to impede or stop the diabetic process described in the previous Diabetes Part 1 blog entry.
The 2009 publication The acute effects of a lunch containing capsaicin on energy and substrate utilisation, hormones, and satiety reports “An acute lunch containing capsaicin had no effect on satiety, EE, and PYY, but increased GLP-1 and tended to decrease ghrelin.” That is, the lunch decreased the hunger protein ghrelin and hunger signaling.
Eat hot red peppers and use hot red pepper sauce!
Spices, tea and caffeine
The 2006 publication Metabolic effects of spices, teas, and caffeine reports “Consumption of spiced foods or herbal drinks leads to greater thermogenesis and in some cases to greater satiety. In this regard, capsaicin, black pepper, ginger, mixed spices, green tea, black tea and caffeine are relevant examples. These functional ingredients have the potential to produce significant effects on metabolic targets such as satiety, thermogenesis, and fat oxidation. A significant clinical outcome sometimes may appear straightforwardly but also depends too strongly on full compliance of subjects. Nevertheless, thermogenic ingredients may be considered as functional agents that could help in preventing a positive energy balance and obesity.”
Eat spicy foods and generously use spices! See the blog posts Spices of life and Rosmarinic acid.
The 2002 publication Dual action of isoprenols from herbal medicines on both PPARgamma and PPARalpha in 3T3-L1 adipocytes and HepG2 hepatocytes reports “Several herbal medicines improve hyperlipidemia, diabetes and cardiovascular diseases. — In this study, we found that several isoprenols, common components of herbal plants, activate human peroxisome proliferator-activated receptors (PPARs) as determined using the novel GAL4 ligand-binding domain chimera assay system with coactivator coexpression. Farnesol and geranylgeraniol that are typical isoprenols in herbs and fruits activated not only PPARgamma but also PPARalpha as determined using the chimera assay system. These compounds also activated full-length human PPARgamma and PPARalpha in CV1 cells. Moreover, these isoprenols upregulated the expression of some lipid metabolic target genes of PPARgamma and PPARalpha in 3T3-L1 adipocytes and HepG2 hepatocytes, respectively. These results suggest that herbal medicines containing isoprenols with dual action on both PPARgamma and PPARalpha can be of interest for the amelioration of lipid metabolic disorders associated with diabetes.” “Farnesol is present in many essential oils such as citronella, neroli, cyclamen, lemon grass, tuberose, rose, musk, balsam and tolu(ref).” Geranylgeraniol is present in Pterodon pubescens Benth seeds which “are commercially available in the Brazilian medicinal plant street market. The crude alcoholic extracts of this plant are used in folk medicine as anti-inflammatory, analgesic, and anti-rheumatic preparations(ref).”
Except for readers who may be deeply into herbal medicine or who visit Brazil frequently, I suggest trying other practical substances like blueberries and tomatoes.
The 2007 paper Active spice-derived components can inhibit inflammatory responses of adipose tissue in obesity by suppressing inflammatory actions of macrophages and release of monocyte chemoattractant protein-1 from adipocytes relates to both spices consumed with foods and spices taken that can be taken as supplements like curcumin and ginger. “Macrophage activation was estimated by measuring tumor necrosis factor-alpha (TNF-alpha), nitric oxide, and monocyte chemoattractant protein-1 (MCP-1) concentrations. The active spice-derived components markedly suppressed the migration of macrophages induced by the mesenteric adipose tissue-conditioned medium in a dose-dependent manner. Among the active spice-derived components studied, allyl isothiocyanate, zingerone, and curcumin significantly inhibited the cellular production of proinflammatory mediators such as TNF-alpha and nitric oxide, and significantly inhibited the release of MCP-1 from 3T3-L1 adipocytes. Our findings suggest that the spice-derived components can suppress obesity-induced inflammatory responses by suppressing adipose tissue macrophage accumulation or activation and inhibiting MCP-1 release from adipocytes. These spice-derived components may have a potential to improve chronic inflammatory conditions in obesity.” Allyl isothiocyanate “is responsible for the pungent taste of mustard, horseradish, and wasabi(ref).” Zingerone gives the zing to ginger.
Eat ginger, mustard and horseradish if you can take it!
The 2010 publication Antidiabetic effects of cinnamon oil in diabetic KK-A(y) mice reports on studying the hypoglycemic effect of cinnamon oil (CO) in a type 2 diabetic animal model. “CO was administrated at doses of 25, 50 and 100mg/kg for 35days. It was found that fasting blood glucose concentration was significantly decreased (P<0.05) with the 100mg/kg group (P<0.01) the most efficient compared with the diabetic control group. In addition, there was significant decrease in plasma C-peptide, serum triglyceride, total cholesterol and blood urea nitrogen levels while serum high density lipoprotein (HDL)-cholesterol levels were significantly increased after 35days. Meanwhile, glucose tolerance was improved, and the immunoreactive of pancreatic islets beta-cells was promoted. These results suggest that CO had a regulative role in blood glucose level and lipids, and improved the function of pancreatic islets. Cinnamon oil may be useful in the treatment of type 2 diabetes mellitus.” There is much current interest in use of cinnamon for treating diabetes. Other relevant 2010 and publications are
· Cinnamon extract regulates glucose transporter and insulin-signaling gene expression in mouse adipocytes,
· Cinnamon: Potential Role in the Prevention of Insulin Resistance, Metabolic Syndrome, and Type 2 Diabetes,
· Cinnamon as a supplemental treatment for impaired glucose tolerance and type 2 diabetes.
Eat cinnamon and drink cinnamon tea!
Foods containing luteolin
Luteolin is another food substance that works against diabetes. “Luteolin is a flavonoid; more specifically, it is one of the more common flavones. — Luteolin is most often found in leaves, but it is also seen in celery, thyme, dandelion, rinds, barks, clover blossom and ragweed pollen. It has also been isolated from Salvia tomentosa. Dietary sources include celery, green pepper, thyme, perilla, chamomile tea, carrots, olive oil, peppermint, rosemary and oregano(ref). the 2009 paper Luteolin, a food-derived flavonoid, suppresses adipocyte-dependent activation of macrophages by inhibiting JNK activation reports “The findings indicate that luteolin can inhibit the interaction between adipocytes and macrophages to suppress the production of inflammatory mediators, suggesting that luteolin is a valuable food-derived compound for the treatment of metabolic syndrome.”
Eat celery, green pepper, thyme, perilla, carrots, olive oil, peppermint, rosemary and oregano and drink chamomile tea!
The 2007 paper Obesity and thermogenesis related to the consumption of caffeine, ephedrine, capsaicin, and green tea and the 2010 oublication Green tea catechins, caffeine and body-weight regulation convey more or less the same bottom-line message. “Positive effects on body-weight management have been shown using green tea mixtures. Green tea, by containing both tea catechins and caffeine, may act through inhibition of catechol O-methyl-transferase, and inhibition of phosphodiesterase. Here the mechanisms may also operate synergistically. A green tea-caffeine mixture improves weight maintenance, through thermogenesis, fat oxidation, and sparing fat free mass. The sympathetic nervous system is involved in the regulation of lipolysis, and the sympathetic innervation of white adipose tissue may play an important role in the regulation of total body fat in general. Taken together, these functional ingredients have the potential to produce significant effects on metabolic targets such as thermogenesis, and fat oxidation.”
Drink green tea and/or take green tea capsules!
I have written before how many of the supplements in the combined anti-aging firewalls supplement regimen target inflammation and perhaps enhance longevity by inhibiting the expression of the cell transcription factor NF-kappaB. In fact, 39 substances in the firewalls regimen do this. Since inflammation and the expression of NF-kappaB play such key roles in the onset and maintenance of Type 2 diabetes, it should be no surprise that many of those same 39 substances are effective at controlling diabetes. This blog entry is already getting very long, so I will limit the discussion to a few key examples: fish oils, curcumin, resveratrol, ginger, and pine bark extract.
Fish oils, DHA and EPA
The 2007 publication Prevention of high-fat diet-induced adipose tissue remodeling in obese diabetic mice by n-3 polyunsaturated fatty acids is one of a number of animal research studies examining the mechanism of how poly unsaturated fatty acids (PUFAs) combat diabetic effects. “OBJECTIVE: Obesity is associated with reduced insulin sensitivity and extensive reorganization of adipose tissue. As polyunsaturated fatty acids (PUFA) appear to inhibit diabetes development, we investigated PUFA effects on markers of matrix remodeling in white adipose tissue. METHODS AND PROCEDURE: Male obese diabetic (db/db) mice were treated with either a low-fat standard diet (LF), or high-fat diets rich in saturated and monounsaturated fatty acids — RESULTS: HF/S treatment increased adipose tissue expression of a number of genes involved in matrix degradation including matrix metalloproteinase (MMP)-12, -14 and cathepsin K, L and S compared with LF. MMP-12 gene was expressed in macrophages and adipocytes, and MMP-12 protein colocalized with both cell types. In addition, mean adipocyte area increased by 1.6-fold in HF/S-treated mice. Genes essential for collagen production, such as procollagen I, III, VI, tenascin C and biglycan were upregulated in HF/S-treated animals as well. N-3 PUFA supplementation resulted in enrichment of these fatty acids in adipose tissue. Moreover, n-3 PUFA inhibited the HF/S-induced upregulation of genes involved in matrix degradation and production I restored mean adipocyte area and prevented MMP-12 expression in macrophages and adipocytes. CONCLUSION: N-3 PUFA prevent high-fat diet-induced matrix remodeling and adipocyte enlargement in adipose tissue of obese diabetic mice. Such changes could contribute to diabetes prevention by n-3 PUFA in obese patients.”
Another relevant publications is the 2006 paper Adipose tissue inflammation induced by high-fat diet in obese diabetic mice is prevented by n-3 polyunsaturated fatty acids.” “n-3 PUFA prevent adipose tissue inflammation induced by high-fat diet in obese diabetic mice, thereby dissecting obesity from adipose tissue inflammation. These data suggest that beneficial effects of n-3 PUFA on diabetes development could be mediated by their effect on adipose tissue inflammation.”
Other relevant publications include the 2009 paper Cellular and molecular effects of n-3 polyunsaturated fatty acids on adipose tissue biology and metabolism, and the 2009 publication n-3 PUFA: bioavailability and modulation of adipose tissue function “In rodents n-3 LC PUFA prevent the development of obesity and impaired glucose tolerance. The effects of n-3 LC PUFA are mediated transcriptionally by AMP-activated protein kinase and by other mechanisms. n-3 LC PUFA activate a metabolic switch toward lipid catabolism and suppression of lipogenesis, i.e. in the liver, adipose tissue and small intestine. This metabolic switch improves dyslipidaemia and reduces ectopic deposition of lipids, resulting in improved insulin signalling. Despite a relatively low accumulation of n-3 LC PUFA in adipose tissue lipids, adipose tissue is specifically linked to the beneficial effects of n-3 LC PUFA, as indicated by (1) the prevention of adipose tissue hyperplasia and hypertrophy, (2) the induction of mitochondrial biogenesis in adipocytes, (3) the induction of adiponectin and (4) the amelioration of adipose tissue inflammation by n-3 LC PUFA.”
It suffices for me to quote from only one of the latest publications relating curcumin to diabetes, the 2010 e-publication Targeting Inflammation-Induced Obesity and Metabolic Diseases by Curcumin and Other Nutraceuticals. “Several spices have been shown to exhibit activity against obesity through antioxidant and anti-inflammatory mechanisms. Among them, curcumin, a yellow pigment derived from the spice turmeric (an essential component of curry powder), has been investigated most extensively as a treatment for obesity and obesity-related metabolic diseases. Curcumin directly interacts with adipocytes, pancreatic cells, hepatic stellate cells, macrophages, and muscle cells. There, it suppresses the proinflammatory transcription factor nuclear factor-kappa B, signal transducer and activators of transcription-3, and Wnt/beta-catenin, and it activates peroxisome proliferator-activated receptor-gamma and Nrf2 cell-signaling pathways, thus leading to the downregulation of adipokines, including tumor necrosis factor, interleukin-6, resistin, leptin, and monocyte chemotactic protein-1, and the upregulation of adiponectin and other gene products. These curcumin-induced alterations reverse insulin resistance, hyperglycemia, hyperlipidemia, and other symptoms linked to obesity. Other structurally homologous nutraceuticals, derived from red chili, cinnamon, cloves, black pepper, and ginger, also exhibit effects against obesity and insulin resistance.”
The 2010 publication Resveratrol attenuates hyperglycemia-mediated oxidative stress, proinflammatory cytokines and protects hepatocytes ultrastructure in streptozotocin-nicotinamide-induced experimental diabetic rats reports “The diminished activities of hepatic enzymic antioxidants as well as the decreased levels of hepatic non-enzymic antioxidants of diabetic rats were reverted to near normalcy by resveratrol administration. Moreover, the histological and ultrastructural observations evidenced that resveratrol effectively rescues the hepatocytes from hyperglycemia-mediated oxidative damage without affecting its cellular function and structural integrity. The findings of the present investigation demonstrated the hepatocyte protective nature of resveratrol by attenuating markers of hyperglycemia-mediated oxidative stress and antioxidant competence in hepatic tissues of diabetic rats.” Other publications carry a similar message including the 2010 publication Ameliorative potential of resveratrol on proinflammatory cytokines, hyperglycemia mediated oxidative stress, and pancreatic beta-cell dysfunction in streptozotocin-nicotinamide-induced diabetic rats. “The results of the present investigation demonstrated that resveratrol exhibits significant antidiabetic potential by attenuating hyperglycemia, enhancing insulin secretion and antioxidant competence in pancreatic beta-cells of diabetic rats.”
The 2008 publication 6-Shogaol and 6-gingerol, the pungent of ginger, inhibit TNF-alpha mediated downregulation of adiponectin expression via different mechanisms in 3T3-L1 adipocytes. “In this study, we demonstrated that the two ginger-derived components have a potent and unique pharmacological function in 3T3-L1 adipocytes via different mechanisms. Both pretreatment of 6-shogaol (6S) and 6-gingerol (6G) significantly inhibited the tumor necrosis factor-alpha (TNF-alpha) mediated downregulation of the adiponectin expression in 3T3-L1 adipocytes.”
The 2006 publication Analgesic, antiinflammatory and hypoglycaemic effects of ethanol extract of Zingiber officinale (Roscoe) rhizomes (Zingiberaceae) in mice and rats reports “The findings of this experimental animal study indicate that Zingiber officinale rhizomes ethanol extract possesses analgesic, antiinflammatory and hypoglycaemic properties; and thus lend pharmacological support to folkloric, ethnomedical uses of ginger in the treatment and/or management of painful, arthritic inflammatory conditions, as well as in the management and/or control of type 2 diabetes mellitus in some rural Africa communities.”
Pine bark extract
Dehydroabietic acid Is a terpenoid contained in pine bark extract. The 2009 paper Dehydroabietic acid, a diterpene, improves diabetes and hyperlipidemia in obese diabetic KK-Ay mice reports “In this study, the effects of dehydroabietic acid (DAA), a diterpene, on glucose and lipid metabolism were examined using obese diabetic KK-Ay mice. We showed here that DAA treatment decreased not only plasma glucose and insulin levels but also plasma triglyceride (TG) and hepatic TG levels. To examine the mechanism underlying the effects of DAA, the production of inflammatory cytokines was measured. It was shown that the DAA treatment suppressed the production of monocyte chemoattractant protein-1 (MCP-1) and tumor necrosis factor-alpha (TNFalpha) (proinflammatory cytokines) and increased that of adiponectin (an anti-inflammatory cytokine). As a result of the changes in the production of inflammatory cytokines caused by the DAA treatment, the accumulation of macrophages in adipose tissues was reduced. These results indicate that treatment with DAA improves the levels of plasma glucose, plasma insulin, plasma TG, and hepatic TG through the decrease in the macrophage infiltration into adipose tissues, suggesting that DAA is a useful food-derived compound for treating obesity-related diseases.”
A final comment
These two blog entries on diabetes have been very long – and I had to cut them off because I could have continued to go on and on citing more and more research publications . There is one important message I hope to get across to my readers: There is a great deal of science behind the lifestyle, dietary and supplement suggestions relating to prevention and control of diabetes, just as there is a great deal of science behind the other suggestions in the anti-aging lifestyle regimen and the combined anti-aging firewalls supplement regimen.
FROM TIME TO TIME, THIS BLOG DISCUSSES DISEASE PROCESSES. THE INTENTION OF THOSE DISCUSSIONS IS TO CONVEY CURRENT RESEARCH FINDINGS AND OPINIONS, NOT TO GIVE MEDICAL ADVICE. THE INFORMATION IN POSTS IN THIS BLOG IS NOT A SUBSTITUTE FOR A LICENSED PHYSICIAN’S MEDICAL ADVICE. IF ANY ADVICE, OPINIONS, OR INSTRUCTIONS HEREIN CONFLICT WITH THAT OF A TREATING LICENSED PHYSICIAN, DEFER TO THE OPINION OF THE PHYSICIAN. THIS INFORMATION IS INTENDED FOR PEOPLE IN GOOD HEALTH. IT IS THE READER’S RESPONSIBILITY TO KNOW HIS OR HER MEDICAL HISTORY AND ENSURE THAT ACTIONS OR SUPPLEMENTS HE OR SHE TAKES DO NOT CREATE AN ADVERSE REACTION.
After age 50 or 60 it seems less protein might help with ageing.
Dietary restriction (DR) extends life span in diverse organisms, including mammals, and common mechanisms may be at work. DR is often known as calorie restriction, because it has been suggested that reduction of calories, rather than of particular nutrients in the diet, mediates extension of life span in rodents. We here demonstrate that extension of life span by DR in Drosophila is not attributable to the reduction in calorie intake. Reduction of either dietary yeast or sugar can reduce mortality and extend life span, but by an amount that is unrelated to the calorie content of the food, and with yeast having a much greater effect per calorie than does sugar. Calorie intake is therefore not the key factor in the reduction of mortality rate by DR in this species.
This cited article and the more-recent research you cited related to glycerol and CR certainly make a compelling case that CR life extension is more a function of what is eaten than simple number of calories consumed. I will see if there is anything in the literature regarding the specific effects of glycerol or yeast in activating/supressing key longevity pathways like TOR and SIRT2. there may be something there simple and highly relevant that has largely been missed so far.
I read about this acai fruit from my friend because she is using it and she told me it is really effective
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Wow! I actually loved this blog. You give me many good data, thanks!
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