Category Archives: Cardiovascular Health

Eat your Fresh Fruit! – for better cardiovascular health: Latest New England Journal April 11, 2016

A recent study released in the April 10 edition of The New England Journal of Medicine demonstrated that fresh fruit consumption was associated with decreased blood pressure and decreased blood glucose.

Fresh Fruit Consumption and Major Cardiovascular disease in China

Increased fresh fruit consumption was associated with decreased risk of cardiovascular disease, decreased cardiovascular death, decreased coronary events, decreased hemorrhagic stroke, and decreased ischemic strokes.


Fruit and vegetable consumption and mortality from all causes, cardiovascular disease, and cancer_ systematic review and dose-response meta-analysis of prospective cohort studies

Increased consumption of fruit and vegetables for the primary prevention of cardiovascular diseases.

Dietary Nitrate Lowers Blood Pressure

Fruit and vegetable consumption and all-cause, cancer and CVD mortality analysis of Health Survey for England data.

Fruit and Vegetable Consumption and Risk of CAD – a metanalysis of cohort studies

Quantity and variety in fruit and vegetable intake and risk of coronary heart disease

Greater Total Antioxidant Capacity from Diet and Supplements Is Associated with a Less Atherogenic Blood Profile in U.S. Adults

Novel insights of dietary polyphenols and obesity

Cruciferous vegetable consumption is associated with a reduced risk of total and Cardiovascular disease mortality

The NEJM study released in this issue death with Chinese populations, some 450,000 Chinese in fact, with no prior stroke or hypertension to avoid confounding factors. IN Western populations, an inverse association had been seen in patients eating 80 gm of fruit a day, leading to a 5% decrease in cardiovascular death.

A low level of fruit intake is associated with a major increased cardiovascular risk rate. The study above chose China, since vegetable intake is high but fresh-fruit intake is much lower.  Cardiovascular disease causes 17 million deaths a year and is especially high in lower income countries. The effect of adding fruit to the diet of people with low consumption rate can detect larger effects.


The association between the level of fruit consumption and cardiovascular risk in our study (a 40% lower risk of cardiovascular death and a 34% lower risk of major coronary events among participants who consumed fresh fruit daily as compared with those who never or rarely consumed fresh fruit) was much stronger than the associations observed in previous studies. < Current NEJM study April 2016.    This study involved some 512,000 people who had low intake of fruit already, making it easy to detect positive benefits. None of the patients had hypertension or Diabetes, and thus were not on any confounding medications. The study also took into account regression dilution bias (changes in baseline characteristics of a population during a study) that may impact findings. 

Fruit is high in fiber, potassium, folate, phytochemicals, and antioxidants all of which may mediate the positive impact of fruit intake.


In conclusion, our evaluation of the relationship between fresh fruit consumption and cardiovascular disease in China showed that the level of fruit consumption was inversely associated with blood pressure and blood glucose levels.

Global and regional mortality from 235 causes of death for 20 age groups in 1990 and 2010 a systematic analysis for the Global Burden of Disease Study 2010.

Up-regulating the Human Intestinal Microbiome Using Whole Plant foods, polyphenols and fiber

Health benefits of fruit and vegetables are from additive and synergistic combinations of phytochemicals

What is Xenohormesis

White Pitaya (Hylocereus undatus) Juice attenuates insulin resistance and hepatic steatosis in obese mice

Greater Total Antioxidant Capacity from Diet and Supplements Is Associated with a Less Atherogenic Blood Profile in U.S. Adults b

Feeding the brain and nurturing the mind linking nutrition and the gut microbiota to brain development

Cultivating healthy growth and nutrition through the gut microbiota.




Eat your greens – chlorophyll metabolites in our blood may be maintaining our blood anti-oxidants.

  • Eat your greens!
    Eat your greens!

    Everyone knows about CoQ10, with many people frequently taking it for ‘vascular health’ . It is true that ubiquinol in the blood stream is an anti-oxidant that helps maintain vascular integrity. Ubiquinol–10  is an endogenously synthesized lipid antioxidant that scavenges free radicals and is involved in a-tocopherol homeostasis. It prevents lipid peroxidation and in the process is oxidized to ubiquinone.

  • 95 % of the quinone is maintained as ubiquinol, which must be regenerated from ubiquinone after it prevents lipid oxidation.
  • The study below demonstrated derivatives of chlorophyll can catalyze the reduction of ubiquinone to generate ubiquinol in plasma. The chlorophyll in our system is obtained from green leafy vegetables, and it is derivatives of the chlorophyll that may be catalyzing the reforming of ubiquinol, rather than ascorbic acid, carotenoid, tocopherol and flavonoid antioxidants that are usually given the credit for this process.
  • In the blood stream, metabolites of chlorophyll , such as chlorophyllide a, pheophytin-a, pheophorbide-a, methyl pheophorbide-a, 10-OH-pheophorbide-a, 10- OH-methyl pheophorbide-a, pyro pheophorbide-a and methyl pyropheophorbide are formed and may catalyze the photoreduction of ubiquinone to ubiquinol.
  •  Both light and light-absorbing chlorophyll metabolites can be present in capillaries, arteries and veins of several animals including humans. If chlorophyll metabolites catalyze the photoreduction of plasma ubiquinol in vivo, it would be a novel mechanism to maintain high levels of plasma ubiquinol – and this is what the paper listed in it’s research proposes, is that light through our skin drives chlorophyl metabolites to regenerate the phytonutrient ubiquinol.
  • Dietary Chlorophyll Metabolites Catalyze the Photoreduction of Plasma ubiquinone
  • Bottom line: Eat your greens and get sunshine!

Consumption of fruits and vegetables was inversely associated with stroke incidence, stroke mortality, ischemic heart disease mortality, and CVD mortality.

Known modifiable risk factors for CVD include smoking, sedentary lifestyle, diet, dyslipidemia, hypertension, obesity, and type 2 diabetes.

The observed protective effect of consuming plant foods on chronic diseases is likely due to their bioactive components.

Plant Bioactives:

  1. Phytosterols are naturally-occurring plant sterols found in the non-saponifiable fraction of plant oils. Plants synthesize several types of phytosterols (e.g., sterols and stanols) that are structurally similar to cholesterol, except for the functional group substitutions on the sterol side chain at the C24 position. Beta-sitosterol (most abundant), campesterol, and stigmasterol comprise almost our entire intake of phytosterols. Since humans do not synthesize phytosterols, they must be obtained from the diet. The main dietary sources of naturally-occurring phytosterols are vegetable oils, nuts, grains and, to a lesser extent, fruits and vegetables. Commonly consumed products that are fortified with phytosterols, such as Benecol™ and Take Control™ are found in many foods. . Benecol spread contains stanol esters derived from tall oil (pine tree wood pulp) and Take Control margarine contains sterol esters from soybeans. Consuming 2–3 g/d of phytosterols from these products resulted in approximately 14% reduction in LDL  with no change in HDL. Thus, both sterols and stanols are equally effective in lowering LDL concentration. NCEP ATP 111 guuidelines: two grams of plant sterol or stanol esters daily for optimal dietary therapy for elevated LDL.
  2. Flavonoids: The most common flavonoids are flavones, flavanols, catechins, and anthocyanins, along with anthoxanthins. There is an inverse relationship between flavonoid intake and chronic diseases including CVD. Red wines contain an abundance of polyphenols including phenolic acids (for example, gallic acid, and caffeic acid), stilbenes (resveratrol), and flavonoids (for example, catechin, epicatechin, quercetin, rutin) . Gallic acid has more antioxidant activity than caffeic acid. Wine polyphenols can induce vasorelaxation via nitric oxide synthesis , decrease platlet aggregation, and decrease inflammatory mediators. Resveratrol is a polyphenol found principally in the skin of grapes and, in lesser amounts, in peanuts. It inhibits both LDL oxidation and platelet aggregation and scavanges free radicals.
  3. Lignans: Lignans are polyphenols found in plants, especially in flaxseed (secoisolariciresinol diglucoside), sesame seeds (sesamin, sesamolin), and soy, followed by whole-grains cereals (syringaresinol), and legumes, including nuts. Fruits and vegetables contain a wide variety of lignans (e.g., matairesinol (MAT), pinoresinol (PINO) and lariciresinol (LARI)) but in minute quantities. The proposed mechanisms by which dietary lignans could reduce the risk of CVD include the phytoestrogenic, and antioxidant activity of these compounds and their metabolites. Some plant lignans such as matairesinol (MAT), secoisolariciresinol (SECO), pinoresinol (PINO), and lariciresinol (LARI) are metabolized by intestinal bacteria to enterolignans (enterodiol and enterolactone) in various proportions.
  4. Resistant starches: Complex carbohydrates derived from starch contribute over half of humans’ daily energy requirements. Starch is a homopolysaccharide made in plants and stored in granules. Amylose and amylopectin are two polymers found in starch and are identified based on the glycosidic bond linking the α-D-glucose monomers. Amylose is a linear polymer with α-(1,4) linkages while amylopectin has linear α-(1,4) linkages and α-(1,6) branch points. There are four types of resistant starches – types one to four. Dietary sources of RS 1 include partially milled grains and seeds. RS 2 can be found in raw potatoes, legumes, just-ripe bananas, and high-amylose maize (HAM). RS 3 results from retrograded foods, such as potatoes, cereals, and breads. Chemically- or physically-modified starch and resistant maltodextrins are known as RS 4 and 5, respectively.  Due to lack of enzymatic hydrolysis, the direct contribution of glucose to blood from RS is minimal and allows for an attenuated post-prandial glycemic response.  Peripheral insulin sensitivity (Si) also improved by approximately 20% in individuals with metabolic syndrome consuming the same amount or RS.  There is  production of short chain fatty acids (SCFA) from RS fermentation by gut microbiota in the large intestine which tereby makes RS bioactive. The SCFA are capable of influencing risk, and even treatment, of NCDs such as diabetes and cancer through several mechanisms: decreasing luminal pH, enhancing mineral absorption, and stimulating the release of two satiety peptides known as glucagon-like peptide -1 (GLP-1) and peptide tyrosine tyrosine (PYY) to the periphery . RS can act as a prebiotic to selectively increase the concentration and viability of certain bacteria, such as Ruminococcus bromii .Intra-individual variation in gut microbiota may influence RS fermentation, the production of SCFA, and upregulation of GLP-1.
  5. Cyclic Dipeptides: Cyclic dipeptides (also known as 2,5dioxopiperazines; 2,5-diketopiperazines; cyclo (dipeptides); or dipeptide anhydrides) are relatively simple compounds and, therefore, are among the most common peptide derivatives found in nature. Consistent with a role for fermentation process in synthesis of cyclic dipeptides is the observation of high levels of cyclo (His-Pro) in foods that undergo fermentation and/or high heat treatment of protein-rich foods. Such examples are nutritional supplements (e.g., TwoCal HN and Jevity), milk, yogurt, sauces, and fermented fish . Active cyclic dipeptides include cyclo (His-Pro), cyclo (Leu-Gly), cyclo (Tyr-Arg), and cyclo (Asp-Pro). Of these only cyclo (his-Pro)[CHP] has been shown to be endogenous to animal kingdom. CHP may act as an appetite suppressant and satiety-inducer.  There is a possible role of CHP in insulin secretion and glucose metabolism.  CHP  causes higher insulin excursions without any change in C-peptide suggesting that CHP may decrease hepatic insulin clearance.    Items with CHP include tuna, fish sauce, Dried Shrimp , Spent Brewer’s Yeast hydrolysate, and others.
  6. Fruit Berries:  Polyphenols found in berries and other plant foods are particularly associated with anti-inflammatory, antioxidant, cardioprotective, and chemopreventive properties. Several compounds contribute to the antioxidant properties of berries and are typically found in the outer parts of the fruit or berry, most often as cinnamic and/or benzoic acid derivatives. Tanins, Anthocyanins,  carotenoids and stilbenes such as resveratrol are present in berries. Some amounts of resveratrol can be found in cranberries, strawberries, and other berries. Chokeberry, bilberry, and blackcurrant berries have the highest antioxidant capacity of the different berry fruits (umol Trolox/g fresh weight), and whole fruit extracts have greater antioxidant activity than many isolated phenolic compounds or vitamins . Strawberries are known to be high in phenolic compounds such as the phenolic acid derivative ellagic acid, and contain a significant amount of vitamin C. Blueberries are noted for a wide variety of anthocyanin compounds, while both cranberries and blueberries also contain significant concentrations of phenolic acids. Anti-oxidants in  Berries provide  anti-inflammatory activity, free radical scavenging and up-regulation of antioxidant enzyme genes, decreased levels and antioxidation of LDL, increases in circulating HDL, inhibition of platelet activation and aggregation, and improvements in endothelial function. Berries have been shown to provide improvements in blood pressure or hypertensive status due to increased NO bioavailability via activation of endothelial NO synthase.

Bioactive Plant Metabolites in the Management of Non-Communicable Metabolic Diseases

Statins’ effect on plasma levels of Coenzyme Q10 and improvement in myopathy with supplementatio

Light-harvesting chlorophyll pigments enable mammalian mitochondria to capture photonic energy and produce ATP  <– we show that mammalian mitochondria can also capture light and synthesize ATP when mixed with a light-capturing metabolite of chlorophyll. To demonstrate that dietary chlorophyll metabolites can modulate ATP levels, we examined the effects of the chlorophyll metabolite pyropheophorbide-a (P-a) on ATP synthesis in isolated mouse liver mitochondria in the presence of red light (lmax5670 nm), which chlorin-type molecules such as P-a strongly absorb (Aronoff, 1950), and to which biological tissues are relatively transparent. We used P-a because it is an early metabolite of chlorophyll, however, most known metabolites of chlorophyll can be synthesized from P-a by reactions that normally take place in animal cells The same metabolite fed to the worm Caenorhabditis elegans leads to increase in ATP synthesis upon light exposure, along with an increase in life span.   Results suggest chlorophyll type molecules modulate mitochondrial ATP by catalyzing the reduction of coenzyme Q, a slow step in mitochondrial ATP synthesis. We propose that through consumption of plant chlorophyll pigments, animals, too, are able to derive energy directly from sunlight. We show that dietary metabolites of chlorophyll can enter the circulation, are present in tissues, and can be enriched in the mitochondria. When incubated with a light-capturing metabolite of chlorophyll, isolated mammalian mitochondria and animal-derived tissues, have higher concentrations of ATP when exposed to light, compared with animal tissues not mixed with the metabolite. The hypothesis is that photonic energy capture through dietary-derived metabolites may be an important means of energy regulation in animals.

  • To synthesize ATP, mitochondrial NADH reductase (complex I) and succinate reductase (complex II) extract electrons from NADH and succinate, respectively. These electrons are used to reduce mitochondrial CoQ10, resulting in ubiquinol (the reduced form of CoQ10). Ubiquinol shuttles the electrons to cytochrome c reductase (complex III), which uses the electrons to reduce cytochrome c, which shuttles the electrons to cytochrome c oxidase (complex IV), which ultimately donates the electrons to molecular oxygen. As a result of this electron flow, protons are pumped from the mitochondrial matrix into the inner membrane space, generating a trans-membrane potential used to drive the enzyme ATP-synthase.
  • Photons of red light from sunlight have been present deep inside almost every tissue in the body. Photosensitized electron transfer from excited chlorophyll-type molecules is widely hypothesized to be a primitive form of light-to-energy conversion that evolved into photosynthesis. Electrons would be transferred by a metabolite of chlorophyll to CoQ10, from a chemical oxidant present in the mitochondrial milieu. Many molecules, such as dienols, sulfhydryl compounds, ferrous compounds, NADH, NADPH and ascorbic acid, could all potentially act as electron donors. Intense red light between 600 and 700 nm has been reported to modulate biological processes. . Exposure to red light is thought to stimulate cellular energy metabolism and/or energy production by, as yet, poorly defined mechanisms. On a clear day the amount of light illuminating your brain would allow you to comfortably read a printed book. Photons between 630 and 800 nm can penetrate 25 cm through tissue and muscle of the calf . Adipose tissue is bathed in wavelengths of light that would excite chlorophyll metabolites. Utilization of these facts may have the potential for new therapies. A potential pathway for photonic energy capture is absorption by dietary-derived plant pigments. Dietary metabolites of chlorophyll can be distributed throughout the body where photon absorption may lead to an increase in ATP .

Chlorophyll-related compounds inhibit cell adhesion and inflammation in human aortic cells.

Chlorophyll Revisited Anti-inflammatory Activities of Chlorophyll a and inhibition of expression of TNFa

An Evidence Based Systematic Review of Chlorophyll by the Natural Standard Research Collaboration

An Evidence Based Systematic Review of Goji Lycium spp by the Natural Standard Research Collaboration

Risk of new-onset diabetes associated with statin use




PCSK-9 inhibitors and neuro-cognitive effects – it’s confusing!


PCSK9 (proprotein convertase subtilisin kexin type 9) binding to LDL receptors on hepatocytes promotes receptor degradation, prevents LDL-C clearance from blood, and increases serum concentrations of LDL-C. Evolocumab and Alirocumab  are human IgG2 monoclonal antibodies that targets PCSK9, prevents it from binding to LDL receptors, and increases hepatic uptake of LDL-C.

The second FDA-approved PCSK9 inhibitor evolocumab (Repatha) appears to be similar in efficacy and safety to alirocumab (Praluent), but no comparative studies are available

  • Concerns are arising that the use of PCSK9  inhibitors are related to cognitive adverse events (CAE).  These events include delirium, cognition and attention disorders, dementia, disturbed thinking and perceptive disorders, and memory impairment.
  • Two trials brought this concern to light: The OSLER study (Evolocumab) and the ODYSSEY LONG TERM study ( Alirocumab). Both trials demonstrates an increased incidence of neurocognitive deficits, but these evnts were SELF-REPORTED events, for which there was no formal neuropsychiatric testing.
  • In the OSLER study for Evolocumab, there were 1104 patients evaluated using Evolocumab (420mg) and standard of care treatment versus standard of care treatment alone, Of all these patients, three reported amnesia and 5 reported memory impairment, whereas none did so in the standard of care group.
  • The treatment patients had visits every 4 weeks versus standard of care (not treated with Evocolumab)  who visited every 12 weeks with physicians, thus creating a potential responder bias by self reporting. Because the treated group was seen three time more frequently, there could be ascertainment bias involved since they had more opportunity to complain.
  • An 11 month follow up showed CAE’s in Evolocumab to be 0.9% versus 0.3% of those in the non-PCSK-9 treated group. There was no association between degree of LDL lowering and the self-reported cognition issues.
  • In the ODYSSEY LONG TERM trial, Alirocumab use was evaluated. The CAE events were 1.2% versus 0.5% in the placebo group similar to the OSLER trial.
  • Again the cognitive effects were all SELF-REPORTED n the above trials.
  • An investigation looking at cognitive issues with PCSK-9 inhibitors is being initiated currently: Evaluating PCSK9 Binding antiBody Influence oN coGnitive HeAlth in High cardiovascUlar Risk Subjects (EBBINGHAUS) ( Identifier: NCT02207634). Participants without dementia or mild cognitive impairment at baseline will be randomized in a double-blind, placebo-controlled, multicenter study to evaluate evolocumab + background statin therapy versus statin therapy alone. The primary outcome will be the Spatial Working Memory test, an assessment of executive function. Results are expected in September 2017 with an enrollment of 4,000 subjects.  ( Early Evidence Linking PCSK9 Inhibitors to Neurocognitive Adverse Events: Does Correlation Imply Causation )
  • You may recall that statins have also faced years of controversy regarding cognitive effects, none of which have panned out. The fact remains that in the OSLER and ODYSSETY trials, there is a 50% reduction in cardiovascular events that offers benefits to a huge group of patients in spite of the neurocognitive risk, much of which is undefined. Remember: correlation does not equal causation and subjectively-reported adverse events are potentially fraught with bias. Even coronary heart disease has been associated with impaired cognition.





Early Evidence Linking PCSK9 Inhibitors to Neurocognitive Adverse Events_ Does Correlation Imply Causation_ – American College of Cardiology Efficacy and Safety of Alirocumab in Reducing Lipids Efficacy and Safety of Evolocumab in reducing lipids and cardiovascular events EfficacySafetyEvolocumabReducingLipids Lowering LDL Cholesterol Is Good, but How and in Whom PCSK9-inhibitors-their-effect-on-Lipoprotein-apheresis-patients-ISFA-May-2015

Safety and efficacy of anti-PCSK9 antibodies



Telomeres: You will age faster if you sit around! Telomere length shortens the more sedentary you are – Insane Medicine

  • A great research article in Mayo Clinic Proceedings, marked below, demonstrates the importance of decreasing our sedentary activities. In the study, they determined that telomere length is shortened by sedentary behaviors, measured in the form of leisure-based screen time. Short telomeres is associated with stress, inflammation,  and a variety of cardiometabolic diseases! Short telomeres are an established characteristic of aging. You want to have a successful aging strategy, hence you want to keep your telomeres long! 🙂
  • The measurement of leukocyte telomere length (LTL)  is a method to determine future health, and short LTL is associated with morbidity and mortality independent of age. In the study, 6405 people ages 20-84 were assessed for leisure time screen-based sedentary behavior, namely television, video games and computer use, and a LTL assay was performed on the participants to determine the length of their telomeres over a certain period of time. It was found that for every hour increase in screen based time, the individual had a 7% increased risk of being in the lowest tertile of telomere length. In other words, the more screen based time that was spent, the greater the chance your telomeres were short enough to put you at the bottom of the study group in regards to telomere length.  Hence you have a higher risk of an early illness or death!
  • Physical activity is associated with greater telomere length up to a certain point.
  • The core findings of people with LTL values that were in the bottom group (short telomeres) was that they were more sedentary, engaged in little moderate to vigorous physical activity, had high CRP levels (inflammation marker), had a higher BMI (fatter), and more likely to have diabetes, hypertension, and coronary artery disease.  The chance of a person falling into this category, again increased by 7% for each hour of screen based  leisure time that they spent.
  • Leukocyte telomere shortening is a marker of cellular aging and also is associated with increased morbidity (high blood pressure/diabetes) and mortality. When LTL become critically shortened, the leukocytes secrete pro-inflammatory cytokines and hence increase the CRP ( a marker of inflammation). Thus being sedentary results in inflammation and modulates your metabolic risk in the wrong direction.  In other words, you age faster!!!
  • The key point: Stay active physically and spend less time on Facebook!!
  • Leisure-Time Screen-Based Sedentary Behavior and Leukocyte Telomere Length: Implications for a New Leisure-Time Screen-Based Sedentary Behavior Mechanism –  Paul Loprinzi

Leisure-Time Screen-Based Sedentary Behavior and Leukocyte Telomere Length: Implications for a New Leisure-Time Screen-Based Sedentary Behavior Mechanism


Other interesting abstracts:

Bey, L. and Hamilton, M.T. Suppression of skeletal muscle lipoprotein lipase activity during physical inactivity: a molecular reason to maintain daily low-intensity activity. J Physiol. 2003; 551: 673–682

Suppression of skeletal muscle lipoprotein lipase activity during physical inactivity: a molecular reason to maintain daily low-intensity activity  Bottom line of article:  Inactivity caused a local reduction of plasma [3H]triglyceride uptake into muscle and a decrease in high density lipoprotein cholesterol concentration. Treadmill walking raised LPL activity approximately 8-fold (P < 0.01) within 4 h after inactivity The striking sensitivity of muscle LPL to inactivity and low-intensity contractile activity may provide one piece of the puzzle for why inactivity is a risk factor for metabolic diseases and why even non-vigorous activity provides marked protection against disorders involving poor lipid metabolism.

Tremblay, M.S., Colley, R.C., Saunders, T.J., Healy, G.N., and Owen, N. Physiological and health implications of a sedentary lifestyle. Appl Physiol Nutr Metab. 2010; 35: 725–740  Sedentarism, active lifestyle and sport: impact on health and obesity prevention

The benefits of regular physical activity have been known since ancient Greek. But in the last Century the scientific knowledge around this topic has progressed enormously, starting with the early studies of JN Morris and RS Paffenberger, who demonstrated that physical activity at work reduced incidence of cardiovascular disease and mortality. In the Harvard alumni study, the lowest risk was associated with a weekly output of 1000 to 2000 kcal performing vigorous activities. Further studies in all age groups have supported these findings and have added that even moderate levels of physical activity provide considerable benefits to health, including lower prevalence of overweight and obesity at all ages. Metabolic fat oxidation rate is highest at exercise intensities between 45 and 65% of VO2max. This means that people must be active regularly and force physiological mechanisms at certain intensities. All this body of evidence has contributed to current WHO physical activity recommendations of 150 min/week of moderate to vigorous physical activity (MVPA) in adults and elderly, and 60 min/day of MVPA in children and adolescents, with additional strength training, apart from adopting an active lifestyle. In the last 50 years, occupational physical activity has been reduced for about 120 kcal/day, and sedentarism has emerged as an additional risk factor to physical inactivity. Even if less than 60 min of TV time in adults have been related to lower average BMI, there is still a need for research to determine the appropriate dose of exercise in combination with sedentary behaviours and other activities in the context of our modern lifestyle in order to prevent obesity at all ages. As public health measures have failed to stop the obesity epidemic in the last 3 decades, there is clearly a need to change the paradigm. The inclusion of sport scientists, physical education teachers and other professionals in the multidisciplinary team which should be responsible for drawing the road map to prevent the increase of the obesity epidemic effectively is a “must” from our point of view.


Physical inactivity as the culprit of metabolic inflexibility: evidence from bed-rest studies

Bergouignan, A., Rudwill, F., Simon, C., and Blanc, S. Physical inactivity as the culprit of metabolic inflexibility: evidence from bed-rest studies. J Appl Physiol (1985). 2011; 111: 1201–1210


The following sequence of events can be hypothesized to explain the physical inactivity-induced metabolic alterations and thus metabolic inflexibility (Fig. 4). The physical inactivity induced by bed rest leads to insulin resistance in skeletal muscle, requiring a hyperinsulinemic response to properly dispose of glucose in daily postprandial conditions, whereas adipose tissue displays an appropriate response. At the same time, muscle fiber type shifts toward fast-twitch glycolytic fibers, and muscle increases glucose uptake and oxidation through insulin-independent pathways. This in turn inhibits fatty acid oxidation and ultimately uptake. During meal ingestion, hyperlipemia occurs due to a decreased plasma clearance of dietary fat. This increases the flux of dietary lipids to organs and results in ectopic fat storage with consequences on insulin sensitivity. The liver displays susceptibility to hyperinsulinemia and increased lipid synthesis and storage that overcomes rate of oxidations. Hepatic steatosis will likely ensue. With a reduced oxidative capacity, the liver will then contribute to an increased rate of atherogenic lipid products (VLDL) in which the contributions of FFA coming from the diet and neolipogenesis to the total VLDL-triglycerides will increase, feed-forwarding hyperlipemia and ectopic fat storage. Concomitantly, the steatotic liver will become insulin resistant and unable to suppress hepatic glucose production, which leads to increased gluconeogenesis and feed-forward worsening of hyperinsulinemia.Inactivity and metabolic inflexibilityHypothetical metabolic alterations cascade induced by bed rest that can explain how physical inactivity induces metabolic inflexibility. VLDL, very-low-density lipoprotein; NAFLD, nonalcoholic fatty liver disease; DAG, diacylglycerol.

Physical activity predicts metabolic flexibility. For an equivalent food quotient, metabolically flexible subjects will greatly increase carbohydrate oxidation after the consumption of a meal despite a low increase in plasma insulin concentration. A metabolically inflexible individual, i.e., a person who also displays an insulin resistance, will display a low increase in carbohydrate oxidation despite an marked elevation in insulin secretion.

Weischer, M., Bojesen, S.E., Cawthon, R.M., Freiberg, J.J., Tybjӕrg-Hansen, A., and Nordestgaard, B.G. Short telomere length, myocardial infarction, ischemic heart disease, and early death. Arterioscler Thromb Vasc Biol.2012; 32: 822–829

Short Telomere Length, Myocardial Infarction, Ischemic Heart Disease, and Early Death  -> Findings: Short telomere length is associated with only modestly increased risk of myocardial infarction, ischemic heart disease, and early death.

Leucocyte telomere length and risk of cardiovascular disease: systematic review and meta-analysis BMJ 2014;349:g4227 Available observational data show an inverse association between leucocyte telomere length and risk of coronary heart disease independent of conventional vascular risk factors. The association with cerebrovascular disease is less certain.

Chronic inflammation induces telomere dysfunction and accelerates ageing in mice  Our results show that chronic inflammation aggravates telomere dysfunction and cell senescence, decreases regenerative potential in multiple tissues and accelerates ageing of mice. Anti-inflammatory or antioxidant treatment, specifically COX-2 inhibition, rescued telomere dysfunction, cell senescence and tissue regenerative potential, indicating that chronic inflammation may accelerate ageing at least partially in a cell-autonomous manner via COX-2-dependent hyper-production of ROS.

Cawthon, R.M. Telomere measurement by quantitative PCR. Nucleic Acids Res. 2002; 30: e47   Telomere measurement by quantitative PCR



Insane Medicine – Akkermansia muciniphila and the Gut biome

  • The bacteria in your gut create a huge ecosystem or biome that has major effects on your overall health. More and more studies are demonstrating this, including the one below.
  • The gut microbiota diversity and function plays a role in the development of obesity and metabolic ailments.
  • Akkermansia muciniphila is a mucin-degrading bacteria found in the mucus layer of the intestine that has been found to help improve your metabolic status by increasing insulin sensitivity and glucose regulation.
  • Obese individuals and those with Type 2 diabetes differ from leaner individuals in the constitution of their gut micobiome and the microbial gene richness. It has been found in mice that higher levels of  mucin-degrading bacteria (Akkermansia muciniphila) are inversely associated with body fat and glucose intolerance. In other words, these bacteria help improve glucose metabolism and improve overall metabolic health.
  • The article below demonstrated that Akkermansia muciniphila, when increased in the gut, resulted in healthier metabolic status in obese people. This was accomplished by caloric restriction, which then resulted in increased microbial gene richness ( a good thing) and improved glucose homeostasis and blood lipids. Following a FODMAP diet also increased Akkermansia muciniphila in the gut.
  • The higher the Akkermansia muciniphila bacteria levels are in the gut, it seems that you will have better glucose metabolism, better waist-to-hip ratios, lower fasting glucose levels, better triglyceride levels,  and better fat distribution.
  • Increasing amounts of fat in the form of fat hypertrophy is a proinflammatory condition and is associated with bad cardiometabolic risk. This inflammatory risk is measured through insulin levels, interleukin-6, lipopolysaccharide levels, and C reactive protein levels in the blood stream. Caloric restriction leads to increased Akkermansia muciniphila and other healthy bacteria, which increases the overall microbial gene richness. These bacteria lower the inflammatory markers through their metabolic activity. This results in better metabolic outcomes.
  • How does this all occur? Akkermansia muciniphila ferments waste products into other items that other beneficial bacteria species can feed on. Short chained fatty acids are one of those items as well as acetate, which becomes an anorectant when absorbed in the body. In other words, you eat less.
  • The key here is that the gut biome plays a tremendous role in our overall health, and caloric restriction results in a  boosting of the healthy richness of our gut biome, which is probably a key part of overall health!

KEY study in GUT :



Dao M, Everard A, et al. Akkermansia muciniphilaand improved metabolic health during a dietary intervention in obesity: relationship with gut microbiome richness and ecology. Gut.2015. 

Gut Bacteria and Food Allergies:

  • Gut bacteria also seem to play an integral role in other aspects of our health including food allergies. The presence of Clostridia in our gut appears to be protective against food allergies by causing the release of Interleukin-22 from gut cells, thereby decreasing permeability of the gut to allergens, which cause allergic reaction. Without gut permeability, the antigens cannot create an allergic immune response. Food allergies have been increasing in recent times due  to modern dietary and hygienic practices, which disturb our natural gut biome.High fat diets, antibiotics,  and formula feeding have all affected our gut bacteria, some of which protect us against food allergies. In a study, it was shown that germ-free mice and mice treated with antibiotics both reacted to peanuts, however, when clostridia was introduced, the reaction went away! This demonstrates how Clostridia decreases food allergies.  The study, “Commensal bacteria protect against food allergen sensitization,” was the source of this information.
  • Clostridia protects against Food Allergies

Insane Medicine – The Lipoprotein-associated phospholipase A2 test for assessing early heart attack risk.

Lipoprotein-associated phospholipase A2 elevation is associated with greater stroke and heart attack risks.
Lipoprotein-associated phospholipase A2 elevation is associated with greater stroke and heart attack risks.

Lipoprotein-Associated_Ph000001 Lipoprotein-Associated_Ph000001b

  • The FDA approved a blood test for Lipoprotein-associated phospholipase A2 (Lp-PLA2) recently. Inflammation in fatty plaques spill out Lp-PLA2 into the blood stream, resulting in elevated levels in individuals with higher risk of heart attack and stroke. Likewise, patients with pre-diabetes tend to have a higher level.
  • Testing for the Lp-PLA2 elevation in patients with intermediate heart attack risk but no prior cardiac history offers the ability to asses for future risk. Elevation of Lp-PLA2 is associated with a double the risk of coronary heart disease and four times the risk of strokes than individuals with low levels of Lp-PLA2.
  • CRP is frequently used as a surrogate of inflammation, but it only tests for generalized body inflammation, whereas the Lp-PLA2 test demonstrates inflammation in the blood vessels themselves! An Lp-PLA2 level greater than 200 ng/mL indicates the need for aggressive cholesterol and blood pressure control.

Insane Medicine – Sedentary Behavior is a disease!

Keep active
Keep active
  • Study after study documents the same finding: Regular physical activity at ANY age plays the major role in maintenance of brain functioning and health. Even if you have been inactive for years, you can benefit by slowly initiating a physical activity program.
  • Sedentary behavior is the enemy. When you exercise, you must  also decrease sedentary behavior throughout the day as well to obtain maximum benefit.
  • Sedentary behavior causes damage to the brain’s structure and per a study in PLOS ONE (9/2014), age-related changes in the brain were more prominent in the hippocampus region (memory-making center of the brain) in patients who were sedentary. Sedentary behavior ROTS your brain!
  • Brain plasticity, the brain’s ability to make new connections in response to it’s environment, is improved with physical activity and exercise. What results is better memory and decision-making skills. This can decrease brain atrophy. On CT scans of the brain, many elderly patients demonstrate shrunken brains, much of which can be reduced by physical activity. Additional benefits of brain-preservation outside of better memory and attention is a positive effect on mood and stress. Physical activity can lower blood pressure, control blood sugar, and reduce obesity, all of which negatively impacts brain functioning.
  • What type of exercises should one do? Aerobic exercises, resistance exercises, and gross motor activities. Again, aerobic activities of 30 minutes a day for 5 out of 7 days a week are an excellent goal. Consider jogging, swimming, tennis, dancing, stair climbing, and bicycling for aerobic activities. Build up your muscles with resistance training such as sit ups, weight lifting, and leg raises. The goal is at least three sessions a week to increase muscle tone and strength, which also helps with balance.  Consider Yoga and Tai Chi to help with movement, balance, and flexibility. Balance and strength are very important to decrease falling risks. In fact, there are numerous studies documenting the positive benefit of Tai Chi on decreasing the rate of falling in elderly people.
  • Between exercising sessions, don’t just sit around – KEEP MOVING! Non-exercise physical activity, such as gardening, laundry, dish washing, and climbing the stairs can add to physical and brain health. These activities help maintain mobility  (American Journal of Preventive Medicine). This type of activity complements the other exercise components. This type of activity can reduce heart attack risk and stroke risk by improving weight as well as lipid levels.

Insane Medicine – Even older people should watch their diet

Successful aging requires continued effort for the best outcome. Do you want to live to one hundred and be bed-bound or live to one hundred and be active? Successfully aging people need to consider healthful behaviors to maintain their independence and health. Conditions that affect people over sixty can be modified and lessened by nutritional strategies:

  1. Cardiovascular diseaseHigh blood pressure, cholesterol/triglycerides, and obesity are modifiable by diet and medication. Weight control allows for better mobility, less pain, and fewer heart attacks. Obesity is associated with sleep apnea, as well, which reduces quality of life because it makes you fatigued in the day time and generally weak.
  2. Cerebrovascular Disease: Such as strokes and dementia are impacted by high blood pressure and diet. First off, quit smoking to decrease your risk of dementia and stroke. Decrease your sodium intake to decrease your blood pressure (1500 mg of sodium a day is about right for an average diet.) Use herbs and spices to flavor your foods. Foods such as cold cuts, cheeses, breads, pizza, pasta dishes, snack foods, and soups have higher levels of sodium, so beware. Consider following the DASH diet:  and 
  3. Diabetes Control: Diabetes affects everything from your eyes to your kidneys. There is a four-fold increased risk of death from heart disease or stroke if you are diabetic. Take your medicines, track your hemoglobin A1C (sugar control measure) and eat  food with a low glycemic index. Eat food with less fat and avoid high-sugar content items, but include more vegetables and whole grains to maintain glucose control. It takes a lot of effort if you are diabetic, so don’t let diabetes take your life one leg at a time!
  4. Cancer: Get your recommended screening examinations. Also, maintain a healthy weight since obese people have higher risks of cancer!
  5. Chronic Kidney Disease: Another disease modifiable by diet control – CKD risk is increased if you have hypertension, diabetes, obesity, or cardiovascular disease. A healthy diet and physical activity will maintain your weight and blood pressure, minimizing aging’s impact on your kidneys!


  • Eat bright colored vegetables (carrots, brocolli) and deep colored fruits (berries) for phytochemical, healthy support.
  • Chose whole, enriched, fortified grains and cereals, i.e. whole wheat bread.
  • Chose low and non-fat dairy products: Yogurt and low-lactose milk
  • Use herbs and spices to add flavors to meals
  • Lots of fluids: no sodas
  • Exercise

Insane Medicine – Ways to help adjust your blood pressure

Control your Blood Pressure for long term health:

  • Eat a better diet and reduce salt intake
  • Be physically active
  • Take your prescribed medications as you and your doctor agree upon
  • Limit alcohol intake
  • Cope with stress more effectively
  • Maintain a healthy weight

According to the latest recommendations, hypertension is now considered to need intervention if it is 150/90 at the age of 60 or older, unless you are diabetic in which blood pressure above 140/90 needs intervention. Pre-hypertension is considered to be 120-139 systolic and 80-89 diastolic (the lower number).

Remember that blood pressure, when untreated, increases your risk of stroke, heart attacks, and peripheral artery disease.

Here are a few details to consider:

  1. Salt substitutes (potassium chloride and magnesium sulfate blended with normal salt) decrease blood pressure per some studies (American Journal of Clinical Nutrition) by ~4.9/1.5 mm of Hg lower. In the United States, most of our added salt comes from processed and packaged foods (80%) and less from the salt shaker. Salt substitutes have less of an impact on blood pressure reduction unless you add extra salt on your food yourself!
  2. Exercise for life: Per a recent article in JACC (Journal of the American College of Cardiology), those who maintain regular exercise throughout their lifespan and maintain fitness will delay the age at which hypertension affects your body. Men who exercise little typically reached a systolic blood pressure of 120 mm of Hg by age 46, whereas the fit individuals reached that number by age 54!
  3. Higher protein intake has been linked to lower average systolic and diastolic blood pressure per a recent study in the American journal of Hypertension. Over an 11 year period, those in the top third of a group consuming a lot of protein were 40 % less likely to develop hypertension than individuals who consumed the least amount of protein. The amount of protein they consumed was 102 grams, more than double the daily value normally recommended. Combining high protein diets with high fiber intake reduces hypertensive development by 59%. the source of protein does not appear to matter, whether it is animal or plant protein. Just eat healthy! The mechanism by which protein intake decreases blood pressure may be a result of amino acids which dilate blood vessels in addition to an overall healthier diet.
  4. Flaxseed is another food product that can be helpful in decreasing blood pressure. Flaxseed works best when it is used to substitute for other food products such as refined grains. Flaxseed has 55 calories per tablespoon, so it does add calories. It also has a lot of omega-3 alpha-linolenic acids in it, in addition to lignans, a fiber-like polyphenol. The amount of fiber and antioxidants in flaxseeds are excellent. In a recent article in the journal Hypertension, 30 grams of milled flaxseed in foods such as bagels, buns, muffins, and pasta resulted in blood pressure reductions of 10/7 mm of Hg. This was as effective as blood pressure medications!


Insane medicine – Replace saturated fats in your diet with Vegetable oils (Linoleic acid) to lower cardiac risk!

Replacing saturated fat with vegetable oil is associated with lower coronary artery disease risk based in a study in Circulation recently released (Circulation. 2014;130:1568-1578).

  1. Exchanging 5% of consumed calories from saturated fat sources (red meat and butter) with foods containing linoleic acid (an n-g fatty acid that is polyunsaturated and found in vegetable oil, seeds, and nuts) can decrease coronary heart disease events by 9%. So swap out your saturated fat sources with polyunsaturated fat to help out your heart!
  2. Linoleic acid (polyunsaturated fat) intake was inversely associated with heart disease, such that the more linoleic acid taken in, the lower the risk of heart disease. At the best outcomes, there was a 15% lower heart-risk and 21% lower death rates in those who consumed the most linoleic acid sources.
  3. Replace butter, lard, and fat from red meat with liquid vegetable oils when you prepare and cook foods.  By replacing saturated fat in this way, total and LDL cholesterol is reduced.
  4. Sources of Linoleic acid (an omega-6 polyunsaturated fat) include: soybean, sunflower, safflower, and corn oil, as well as nuts and seeds.
  5. Fats have 9 calories per gram. Use 1.5-3 tablespoons of vegetable oil daily to get 5-10% of calories from linoleic acid (100-200 calories total) It is important to replace saturated fat with these sources of polyunsaturated fats (linoleic acid) and not just adding this to the total fat intake.
  6. Linoleic acid does not promote inflammation based on a neutral effect on inflammatory markers or arachidonic acid levels (which increase in inflammation).

Cooking oil examples:

Safflower oil – 78 % PUFA (Linoleic acid)

Sunflower oil – 69% PUFA (Linoleic acid)

Corn oil – 62%

Soybean oil  – 61 %

Peanut Oil  – 34%

Canola oil  – 29%

Lard – 12 %

Palm oil – 10%

Olive oil  – 9%

Butterfat  – 4%

Palm kernel oil  – 2%

Coconut oil – 2%


General notes about fats:

  • Greater intake of trans-fats (hyrogenated oil for example) relative to polyunsaturated fats (PUFA) is associated with higher cardiac risk. N-3 omega fatty acids and alpha-linoleic (ALA), also an n-3 fatty acid) are associated with good cardiac risk. Linoleic acid (LA) , an n-6 PUFA most commonly eaten in the Western diets, also has been shown to be beneficial in preventing cardiac risk, but less investigation had been done regarding this fatty acid. Linoleic acid reduces LDL levels, which is a positive effect for decreasing cardiac risk. LA can be elongated into arachidonic acid, which is inflammatory and thrombogenic (blood clot forming). Studies have shown that LA is in fact not pro-inflammatory in the body. It does not increase C-reactive protein . It also has no effect on other inflammatory marker such as cytokines, fibrinogen, soluble vascular adhesion molecules, plasminogen activator inhibitor type 1, or tumor necrosis factor-α.
  • There appears to be a linear response to increasing LA intake – as one takes in more LA, there is less coronary events (heart attacks) and less death! Thus n-6 fatty acids (Linoleic acid) has cardioprotective effects! Increasing LA intake by 5% led to 9% less coronary heart disease and 13% less death!
  • It had been assumed that LA is converted to arachidonic acid (AA), which is inflammatory. AA  is the main precursor of eicosanoids with inflammatory and thrombogenic properties, such as prostaglandin E2, thromboxane A2, and leukotriene B4. It has been found, however, that the conversion of LA to AA is tightly controlled in the body, thus there is no increase in inflammation.