Saturday, May 31, 2008

Wheat: Would You Give Your Kids Crack?

Often the comments on Dr. Davis' HeartScanBlog are as insightful as his revolutionary ideas and core concepts. One vital core concept is wheat-cessation. From the entry 'I gained 30lbs from one cracker', Anne said... "Wheat protein contains a number of opioid peptides which can be released during digestion. Some of these are thought to affect the central and peripheral nervous systems. When I gave up gluten, I felt much worse for a few days. This is a very common reaction in those who stop eating gluten cold turkey." May 23, 2008

  • Fukudome S, et al. Opioid peptides derived from wheat gluten: their isolation and characterization. FEBS Lett. 1992 Jan 13;296(1):107-11.
    Four opioid peptides were isolated from the enzymatic digest of wheat gluten. Their structures were Gly-Tyr-Tyr-Pro-Thr, Gly-Tyr-Tyr-Pro,Tyr-Gly-Gly-Trp-Leu and Tyr-Gly-Gly-Trp, which were named gluten exorphins A5, A4, B5 and B4, respectively. The gluten exorphin A5 sequence was found at 15 sites in the primary structure of the high molecular weight glutenin and was highly specific for delta-receptors. The structure-activity relationships of gluten exorphins A were unique in that the presence of Gly at their N-termini increased their activities. Gluten exorphin B5, which corresponds to [Trp4,Leu5]enkephalin, showed the most potent activity among these peptides. Its IC50 values were 0.05 microM and 0.017 microM, respectively, on the GPI and the MVD assays. PMID: 1309704

It's hard to give up wheat for most of us on the 'spectrum'... kinda like giving up narcotics (opioids). The withdrawal won't kill you like alcohol (seizures, DTs) or benzo withdrawal (seizures), but opioid, tobacco, and caffeine cessation share similar characterics with that of wheat cessation. For one, wheat digestion releases several feel-good chemicals called opioid peptides which provide a temporary sensation of satisfaction and satiation (basically a carb dose-dependent 'high'). Studies demonstrate that wheat can actually deliver equivalent doses of morphine (see below). The wheat chemicals are extremely short-lived and their quick drop in the blood concentrations leads to cravings for more wheat/carbs that can be difficult to control.... in fact they can be downright all-consuming and overwhelming for some (even those who work out like mad creatures *heh*).

Add in insulin surges and subsequent metabolic derangement and you've got a formula for an endless cycling of unsatisfying-feeding/craving. One of the most potent wheat opioid peptides B5 causes 'man-boobs' (as referenced by Kramer ala Seinfeld).
  • Fanciulli G, et al. Gluten exorphin B5 stimulates prolactin secretion through opioid receptors located outside the blood-brain barrier. Life Sci. 2005 Feb 25;76(15):1713-9. PMID: 15698850

It's enough to make you hear voices 'eat me' 'EAT ME'. Here's the link with schizophrenia, one of many neuropsych conditions which are related to toxic effects of wheat and opioid peptides. Can food make you crazy? Apparently for many humans, yes.
  • J Hum Nutr. 1980 Apr;34(2):107-12. Diet (gluten) and schizophrenia. Ross-Smith P, Jenner FA. Four aspects of clinical evidence for an association between gluten and schizophrenia are examined. The scientific evidence for the role of gluten is set out. Finally, reference is made to other dietary approaches. PMID: 6989901
  • Peptides. 1984 Nov-Dec;5(6):1139-47. Demonstration of high opioid-like activity in isolated peptides from wheat gluten hydrolysates. Huebner FR, Lieberman KW, Rubino RP, Wall JS.
    Because of a possible relationship between schizophrenia and celiac disease, a condition in some individuals who are sensitive to wheat gluten proteins in the diet, there has been interest in observations that peptides derived from wheat gluten proteins exhibit opioid-like activity in in vitro tests. To determine the origin of the peptides exhibiting opioid activity, wheat proteins were fractionated by size (gel filtration), by charge differences (ion exchange chromatography) and by differences in hydrophobicity (reversed-phase HPLC). These fractions were hydrolyzed by pepsin or pepsin and trypsin and the resulting peptides separated by gel filtration chromatography. The separated peptides were tested for opioid-like activity by competitive binding to opioid receptor sites in rat brain tissue in the presence of tritium-labeled dihydromorphine. The peptides showed considerable differences in activity; while some peptides exhibited no activity, 0.5 mg of the most active peptides were equivalent to 1 nM of morphine in the binding assay. The most active peptides were derived from the gliadin fraction of the gluten complex. PMID: 6099562

Would you feed your children crack-cocaine?

(yes, I admit we do when we don't plan ahead)

'Trigger' foods we avoid because they make us fall off the proverbial band wagon...
--Pepperidge farm GOLDFISH crackers
--Wheat thins
--Any breakfast cereal (hardly do we shop the inner aisles anymore)
--Trader Joe's frozen chocolate chip cookies

Why is wheat associated with so many autoimmune conditions?

The opioid peptides from wheat appear to trigger 'civil wars' and 'civil unrest' between the immune system and different organs in our bodies (including the Thyroid -- which HeartHawk is currently discussing)? Not only are wheat opioid peptides implicated in wreaking havoc on the immune system, but also in causing inordinate amounts of inflammation. And . . . inflammation leads to lymphoma (see end), cancer, and heart/vascular disease.
Manifestations of silent celiac disease
(predominantly extra-intestinal):
Dermatitis herpetiformis
Autoimmune disorders (incl Hashimoto's, Grave's,
Sjögren’s, Type 1 DM,
Biliary cirrhosis, Psoriasis
Crohn's, Addison's)
Neurological disorders
Epilepsy with cerebral calcification
Cerebellar ataxia
Non-alcoholic fatty liver disease (NAFLD)
Unexplained chronic hypertransaminasemia

The above list originates from the below review article (full text here). If primary focal points of celiac-related inflammation leads to lymphoma (see last citation), then can silent asymptomatic celiac disease also cause heart disease? I believe so and that is why Dr. Davis' assertion for a wheat-cessation program as critical component in the plaque regression process. Are you getting tired of the 'low-fat' mantra? It's interesting how cholesterol and fat has yet to be blamed as the cause for cancer like they have for everything else.... HHhhhmmmm..... Does cholesterol really kill us? What is causing the rise in the conditions listed above? Including autism as well (see next to the last citation)?

Has the culprit always been wheat-c-a-r-b-o-h-y-d-r-a-t-e-s?

These scientists Ch'ng et al note a phenomenal explosion in the presentation of celiac conditions (silent and non-silent) in the last 30yrs. Is it coincidental this mirrors changes in the pathetic SAD (standard American diet) and low-fat 'paradigm shift' to an over-reliance on wheat and whole-grains? (Is whole-grains just whole-cr**p?) The celiac researchers report that most individuals with celiac disease have subtle or NO SYMPTOMS at all. In fact many test false negatively secondary to the changes in immunity (reduced IgA). Can treatment change the natural course or prevent autoimmune conditions (like Hashimoto's and Grave's disease)? Here at TYP, we strongly believe complete wheat withdrawal reverses many things. Including heart disease! These scientists summarize how research supports the improvement of many non-silent celiac disorders and the significant correction and resolution in auto-antibodies associated with Thyroid conditions.
  • Ventura et al 39 found that diabetes- and thyroid-related antibodies tended to disappear following a gluten-free diet (11.1% at diagnosis, 5.6% at 6 months and none at 12 or 24 months follow-up for diabetes related antibodies and 14.4%, 11.1%, 6.6% and 2.2% for thyroid related antibodies, respectively)
  • Identifying and treating CD in high-risk patients should confer benefit in reducing complications such as malabsorption, infertility, osteoporosis and lymphoma.95,96

Ch'ng CL, Jones MK, Kingham JG. Celiac disease and autoimmune thyroid disease. Clin Med Res. 2007 Oct;5(3):184-92.
Celiac disease (CD) or gluten sensitive enteropathy is relatively common in western populations with prevalence around 1%. With the recent availability of sensitive and specific serological testing, many patients who are either asymptomatic or have subtle symptoms can be shown to have CD. Patients with CD have modest increases in risks of malignancy and mortality compared to controls. The mortality among CD patients who comply poorly with a gluten-free diet is greater than in compliant patients.The pattern of presentation of CD has altered over the past three decades. Many cases are now detected in adulthood during investigation of problems as diverse as anemia, osteoporosis, autoimmune disorders, unexplained neurological syndromes, infertility and chronic hypertransaminasemia of uncertain cause. Among autoimmune disorders, increased prevalence of CD has been found in patients with autoimmune thyroid disease, type 1 diabetes mellitus, autoimmune liver diseases and inflammatory bowel disease. Prevalence of CD was noted to be 1% to 19% in patients with type 1 diabetes mellitus, 2% to 5% in autoimmune thyroid disorders and 3% to 7% in primary biliary cirrhosis in prospective studies. Conversely, there is also an increased prevalence of immune based disorders among patients with CD.The pathogenesis of co-existent autoimmune thyroid disease and CD is not known, but these conditions share similar HLA haplotypes and are associated with the gene encoding cytotoxic T-lymphocyte-associated antigen-4. Screening high risk patients for CD, such as those with autoimmune diseases, is a reasonable strategy given the increased prevalence.Treatment of CD with a gluten-free diet should reduce the recognized complications of this disease and provide benefits in both general health and perhaps life expectancy. It also improves glycemic control in patients with type 1 diabetes mellitus and enhances the absorption of medications for associated hypothyroidism and osteoporosis. It probably does not change the natural history of associated autoimmune disorders. PMID: 18056028

Kawashti MI, Amin OR, Rowehy NG. Possible immunological disorders in autism: concomitant autoimmunity and immune tolerance. Egypt J Immunol. 2006;13(1):99-104.
Autism is a pervasive developmental disorder that affect children early in their life. Immunological disorders is one of several contributing factors that have been suggested to cause autism. Thirty autistic children aged 3-6 years and thirty non-autistic psychologically-free siblings were studied. Circulating IgA and IgG autoantibodies to casein and gluten dietary proteins were detected by enzyme-immunoassays (EIA). Circulating IgG antibodies to measles, mumps and rubella vaccine (M.M.R) and cytomeglovirus were investigated by EIA. Results revealed high seropositivity for autoantibodies to casein and gluten: 83.3% and 50% respectively in autistic children as compared to 10% and 6.7% positivity in the control group. Surprisingly, circulating anti-measles, anti-mumps and anti-rubella IgG were positive in only 50%, 73.3% and 53.3% respectively as compared to 100% positivity in the control group. Anti-CMV IgG was positive in 43.3% of the autistic children as compared to 7% in the control group. It is concluded that, autoimmune response to dietary proteins and deficient immune response to measles, mumps and rubella vaccine antigens might be associated with autism, as a leading cause or a resulting event. Further research is needed to confirm these findings. PMID: 17974154

Hoggan R. Considering wheat, rye, and barley proteins as aids to carcinogens. Med Hypotheses. 1997 Sep;49(3):285-8. The increased incidence of lymphoma in celiac sprue (CS) is well documented, and the risk of developing this malignancy is 40-100-fold greater than in the general population. The author believes that gluten may also be at the root of lymphomas in asymptomatic and latent celiac sprue, as well. Among the 20-30% of the population which has the HLA factors most common in celiac, increased intestinal permeability leads to absorption of macromolecular peptides with opioid activity, which derive from pepsin digests of wheat. The presence, in the bloodstream, of these peptides may increase the risk of lymphomas for the entire hereditary group, which includes CS. Several processes contribute to the effect that is herein hypothesized, including opioid attachment at the hypothalamic-pituitary-adrenal axis (HPA), and subsequent downregulation of production of natural killer cells. This may offer an explanation for our longstanding awareness that there is an 'impaired lymphocyte reactivity against tumor cells in patients with coeliac disease' which may also apply to first-degree relatives with the same HLA markers. PMID: 9293475

Thursday, May 29, 2008

Sarcopenia: 'Poverty of the Flesh' (Greek)

Sarcopenia is a clinical term referring to the loss of muscle mass, strength and function. Starting in our 30s - 40's we begin to lose lean skeletal muscle mass at an average rate of 5% annually. The value of skeletal muscle mass for heart protection cannot be underestimated. Muscle mass, movement, and many dietary components maintain a low inflammatory status in our bodies via the PPAR-Delta receptor and other critical mechanisms. Decline of mass may be age-related but more and more, dysfunction is a sign of the times -- as a society we engage in less and less physical/intense activities, eat more and more excessive nutrient-poor foods, and are prodigiously sedentary for extended periods of time with 'time-saving' devices. (We lost our TV remote control recently (we don't even watch much TV) and boy we've been a bit more active...) Figure 1. Identical twins of different body size and composition due to different training regimes (endurance running vs. field, including dynamic intense and resistance training. Rennie MJ. Body maintenance and repair: how food and exercise keep the musculoskeletal system in good shape. Exp Physiol. 2005 Jul;90(4):427-36. (the G. L. Brown Prize Lecture)

Movement appears more crucial for certain insulin-resistant individuals (including myself) due to our genes. Movement does not need be structured or scripted activity. All physical movement in essence is effective. This includes housekeeping, car washing, hunting/gathering... (even s..e..x..) counts. And movement appears to defy physics. The more movement engaged... and the more intense... the less effort later. (???!) Is that like life? The more we love 'n give... the more we l-i-v-e?

Variations in PPARD determine the change in body composition during lifestyle intervention: a whole-body magnetic resonance study. Thamer C, et al. J Clin Endocrinol Metab. 2008 Apr;93(4):1497-500.

CONTEXT: We recently demonstrated that single-nucleotide polymorphisms (SNPs) in the peroxisome proliferator-activated receptor-delta gene (PPARD), i.e. rs1053049, rs6902123, and rs2267668, affect the improvement of mitochondrial function, aerobic physical fitness, and insulin sensitivity by lifestyle intervention (LI).

OBJECTIVE: The objective of the study was to determine whether the aforementioned PPARD SNPs influence the change in body composition and ectopic fat storage during LI.

DESIGN: A total of 156 subjects at an increased risk for type 2 diabetes were genotyped for rs1053049, rs6902123, and rs2267668 and participated in a LI program. Body fat depots, ectopic liver fat, and muscle volume of the leg were quantified using magnetic resonance spectroscopy and imaging.

RESULTS: With regard to body composition, carriers of the minor SNP alleles displayed reduced responses to LI, i.e. LI-induced reduction in adipose tissue mass (nonvisceral adipose tissue: rs1053049, P = 0.02; rs2267668, P = 0.04; visceral adipose tissue: rs1053049, P = 0.01) and hepatic lipids (rs1053049, P = 0.04; rs6902123, P = 0.001; independent of changes in adiposity) as well as LI-induced increase in relative muscle volume of the leg (rs1053049, P = 0.003; rs2267668, P = 0.009) were less pronounced in homo- and heterozygous carriers of the minor alleles as compared with homozygous carriers of the major alleles.

CONCLUSION: SNPs rs1053049, rs6902123, and rs2267668 in PPARD affect LI-induced changes in overall adiposity, hepatic fat storage, and relative muscle mass. Our findings provide a mechanistic explanation for the involvement of these genetic variations in the development of insulin resistance and type 2 diabetes. PMID: 18252792

All the PPAR receptors have similar ligands -- endogenous and exogenous fatty acids (short-chain, medium-chain, long-chain, MUFA, PUFA, SFA, etc) and eicosanoids (steroidal products from the prostaglandin cascade, including COX derivatives). They truly are pivotal controllers when all lifestyle and nutritional factors are optimized. Although such a wide-range of substances can bind and activate these receptors, Amino Acids (via the mTOR pathway) appear to be one the most potent stimulators of PPAR. Amino Acid sufficiency can determine and maximize all the functions of PPAR-Gamma (and Alpha and Delta) -- metabolism, maintenance and synthesis of muscle fibers, thermogenesis, burning fat, storing fat, and the overall balancing of energy. Not only can PPARs regulate diabetes/insulin resistance and heart disease, but with their optimization of function, PPARs can also reverse these conditions. PPARs ameliorate atherosclerosis. Both food and omega-3 trials and drug (alpha, gamma, delta) trials demonstrate this already.

Don't be sarcopenic... Build a wealth of heart protection in your flesh. How much meaningful movement do you have in your daily life?

Regulation of peroxisome proliferator-activated receptor-gamma activity by mammalian target of rapamycin and amino acids in adipogenesis.
Kim JE, Chen J. Diabetes. 2004 Nov;53(11):2748-56.

Adipocyte differentiation is a developmental process that is critical for metabolic homeostasis and nutrient signaling. The mammalian target of rapamycin (mTOR) mediates nutrient signaling to regulate cell growth, proliferation, and diverse cellular differentiation. It has been reported that rapamycin, the inhibitor of mTOR and an immunosuppressant, blocks adipocyte differentiation, but the mechanism underlying this phenomenon remains unknown. Here we show that mTOR plays a critical role in 3T3-L1 preadipocyte differentiation and that mTOR kinase activity is required for this process. Rapamycin specifically disrupted the positive transcriptional feedback loop between CCAAT/enhancer-binding protein-alpha and peroxisome proliferator-activated receptor-gamma (PPAR-gamma), two key transcription factors in adipogenesis, by directly targeting the transactivation activity of PPAR-gamma. In addition, we demonstrate for the first time that PPAR-gamma activity is dependent on amino acid sufficiency, revealing a molecular link between nutrient status and adipogenesis. The results of our further investigation have led us to propose a model in which the mTOR pathway and the phosphatidylinositol 3-kinase/Akt pathway act in parallel to regulate PPAR-gamma activation during adipogenesis by mediating nutrient availability and insulin signals, respectively. It is interesting that troglitazone (a thiazolidinedione drug WHICH BINDS PPAR-Gamma) reversed the inhibitory effects of rapamycin and amino acid deprivation, implicating therapeutic values of thiazolidinedione drugs to counter certain side effects of rapamycin as an immunosuppressant. PMID: 15504954

(Diagram from here; Williamson DL, et al. Exercise-induced alterations in extracellular signal-regulated kinase 1/2 and mammalian target of rapamycin (mTOR) signalling to regulatory mechanisms of mRNA translation in mouse muscle. J Physiol. 2006 June 1; 573(Pt 2): 497–510. )

Monday, May 26, 2008

PPAR-Delta: Dagger in the Heart of CAD

(Proteins = amino acids)

PPAR-Delta is part of the family of peroxisome proliferator-activated receptors (PPARs). This receptor family is responsible for cueing in environmental nutrients. In evolutionary terms, survival depended on nutrients in the environment and the ability for the human body to adapt to low nutrients vs. plentiful nutrients it is hypothesized to determine inflammatory status, growth, reproduction and development. Nutrient factors like dietary fats and protien bind or regulate PPAR receptors, thus these receptors have been termed 'nutrient sensors.'

How is this wonderful transcriptional 'switch' turned on? What degrades its amazing anti-inflammatory and muscle/metabolism-building functions? PPAR-Delta works through the mTOR pathway which reminds me enormously of the Norse god THOR which shares similar attributes -- invincibility, strength and virility. Can PPAR-Delta be the dagger in the heart of heart disease?

FIGURE (below)
Therapeutic targets of PPARδ in the metabolic syndrome. Receptor activation improves multiple aspects of the metabolic syndrome through tissue- and cell-specific effects. In skeletal muscle, PPARδ regulates fatty acid transport and oxidation, thermogenesis, and the formation of slow-twitch muscle fibers, resulting in enhanced endurance performance. It likewise activates fatty acid transport and oxidation as well as thermogenesis in adipose tissue, retarding weight gain. PPARδ regulates the availability of BCL-6, an inflammatory suppressor protein released upon ligation of PPARδ, thereby functioning as an “antiinflammatory switch” to control macrophage-elicited inflammation and atherogenesis. In the liver, PPARδ activation suppresses glucose production by upregulating the pentose phosphate shunt. PPARδ activation also improves atherogenic dyslipidemia by raising serum HDL cholesterol levels via unclear mechanisms. Additionally, PPARδ activation in the heart enhances contractile function and may improve cardiomyopathy.

PPAR delta: a dagger in the heart of the metabolic syndrome.
Barish GD, et al. Howard Hughes Medical Institute, Salk, La Jolla CA. J Clin Invest. 2006 Mar;116(3):590-7.
Obesity is a growing threat to global health by virtue of its association with insulin resistance, glucose intolerance, hypertension, and dyslipidemia, collectively known as the metabolic syndrome or syndrome X. The nuclear receptors PPARalpha and PPARgamma are therapeutic targets for hypertriglyceridemia and insulin resistance, respectively, and drugs that modulate these receptors are currently in clinical use. More recent work on the less-described PPAR isotype PPARdelta has uncovered a dual benefit for both hypertriglyceridemia and insulin resistance, highlighting the broad potential of PPARdelta in the treatment of metabolic disease. PPARdelta enhances fatty acid catabolism and energy uncoupling in adipose tissue and muscle, and it suppresses macrophage-derived inflammation. Its combined activities in these and other tissues make it a multifaceted therapeutic target for the metabolic syndrome with the potential to control weight gain, enhance physical endurance, improve insulin sensitivity, and ameliorate atherosclerosis. PMID: 16511591

Synthetic analogues of chemicals that bind PPAR-Delta are being elucidated. In animal (and human) studies, their extreme benefits have been shown on lipids as well as reductions in insulin and improvement in insulin sensitivity. Barish et al summarize much of the current research on PPAR-Delta, including astounding trends in reductions in small dense atherogenic LDL, increases HDL, lowering of TGs, as well as the drops in insulin.

"High-affinity PPARδ ligands have revealed an important role for PPARδ in lipoprotein metabolism. Treatment of insulin-resistant obese rhesus monkeys with the PPARδ-selective agonist GW501516 resulted in a dramatic 79% increase in HDL-C, a 56% decrease in triglycerides, and a 29% decrease in LDL cholesterol (33). The profound increase in HDL cholesterol levels correlated with an increase in number, not size, of HDL particles and was accompanied by increased serum levels of the HDL-associated apolipoproteins apoA-I, apoA-II, and apoC-III (33). In addition, fasting insulin levels declined by up to 48% in the PPARδ drug–treated animals (33). Obese and nonobese mice similarly develop an increase of up to 50% in HDL cholesterol levels when treated with PPARδ agonists (34, 35). The mechanism by which PPARδ activation raises HDL cholesterol levels remains to be elucidated, but studies to date indicate that expression of the reverse cholesterol transporter ABCA1 is enhanced in some tissues upon exposure to PPARδ agonists, including human and mouse macrophages as well as human intestinal cells and fibroblasts (33, 35). Additional work suggests that PPARδ activation reduces intestinal cholesterol absorption via downregulation of the Niemann-Pick C1–like 1 gene (NPC1L1) (35). NPC1L1 is a key mediator of intestinal cholesterol absorption and a putative target for the clinically used cholesterol absorption inhibitor ezetimibe (ZETIA). "

However, like all synthetic, fake analogues which try to copy and mimic our own natural endogenous nutritional factors (Dr. Davis recently discussed) that we consume or make on our own, these agents so far are not the 'magic bullet' researchers hoped for. In this trial, there are questionable effects on colon carcinogenesis in APCmin mice with one synthetic analogue GW501516 (and other cancer lines). This reminds me of other failed clinical trials where synthetic vitamins or hormones caused poor outcomes (CARET, WHI, etc). Natural ligands seem to be the most optimal binders to our natural receptors.

"Moreover, PPARδ agonists enhanced β-oxidation in 3T3-L1 preadipocytes by 50% (39). Most importantly, PPARδ ligands retard weight gain in models of high-fat diet–induced obesity (39, 40). These results suggest that PPARδ synthetic drugs may be therapeutic as antiobesity agents. Short-term (4-month) treatment of obese rhesus monkeys with variable doses of GW501516 did not affect body weight, however, so it remains to be determined whether long-term administration of PPARδ drugs will control body weight in monkeys and humans (33)."

The key may be perhaps... muscle. Isn't the heart one of the most important muscles? It beats every second of every minute of our lives, right? Nearly 100,000 times per day.

Metabolic 'remodeling' in the muscles activates PPAR-Delta; fasting, exercise training, and diabetes can affect it. The end result is prevention of obesity/weight gain and potently sensitizing glucose uptake.

"Skeletal muscle is a key metabolic tissue, accounting for approximately 80% of insulin-stimulated glucose uptake. It is composed of heterogeneous myofibers that differ in their metabolic and contractile properties, including oxidative slow-twitch (type I), mixed oxidative/glycolytic fast-twitch (type IIA), and glycolytic fast-twitch (type IIB) forms
41). Oxidative myofibers preferentially express enzymes that oxidize fatty acids and contain slow isoforms of contractile proteins, whereas glycolytic myofibers predominantly metabolize glucose and are composed of fast contractile protein isoforms (41, 42). Skeletal muscle is highly
plastic, adapting to environmental challenges by regulating the composition of slow- and fast-twitch myofibers. Interventions including endurance exercise, physical inactivity, and metabolic diseases such as type 2 diabetes mellitus can induce the trans-differentiation of myofibers (

"PPARδ’s regulation of metabolic and fiber type status has several physiological implications. First, the presence of an increased proportion of oxidative slow-twitch fibers is predicted to decrease skeletal muscle fatigability. For example, increased endurance in marathon runners is linked to a higher proportion of oxidative slow-twitch fibers in their skeletal muscles. Mice with muscle-specific VP16-PPARδ transgenes have strikingly higher treadmill endurance capacity, running twice as long and far as wild-type mice (WOW -- super-mice! PPAR-Delta doubles the distance!) (
48). Second, oxidative fibers have a tremendous impact on fatty acid homeostasis. Both obesity and insulin resistance are linked to a decrease in the proportion of oxidative slow-twitch fibers in skeletal muscle (5256). Muscle-specific VP16-PPARδ transgenic mice, which have a higher proportion of oxidative slow-twitch fibers, are resistant to high-fat diet–induced obesity (48). Activation of PPARδ during high-fat feeding (In Lab language, translates to 'HIGH CARB' lab chow -- c-a-r-b is the context to concentrate on.) increases disposal of lipid in skeletal muscles, preventing the storage of excess fat in adipocytes and weight gain (39, 40, 49)."

PPAR-Delta activation may be the most heart-protective of all the PPAR receptor subtypes -- PPARalpha and PPARgamma have primary tissue expression, however PPARdelta is expressed strongly ubiquitiously.

Undoubtedly, this receptor has the most power to shield the heart from shifting to inferior energy sources (glucose) and developing inelasticity and stiffness in heart muscle fibers. What has been shown to activate PPAR-Delta? Protein intake (see end), fatty acid intake, movement (see end). What has been shown definitely to de-activate PPAR-Delta? The amount of unliganded receptors appears to predict the inflammatory status, according to Takahashi S, et al. (New therapeutic target for metabolic syndrome: PPARdelta. Endocr J. 2007 Jun;54(3):347-57). Paraplegia (see later). In other words, long periods of physical inactivity and sedentary lifestyles allow this pivotal anti-inflammatory 'switch' to be turned off (which can later lead to heart disease, heart failure, MetSyn, insulin resistance, and even cancer in vitro here and here).

A future blog topic is cardiac energetics (and other laws of physics). Our heart and skeletal muscles prefer combusting fatty acids, not glucose, for energy. Glycogen (glucose stored in muscles) is more like kindling and twigs to a fire. What fuels a nice roaring fire? Nice l-o-g-s... For burning PHAT (!!) flaming fires, our bodies go to temporarily-stored fatty acids in skeletal muscles... then next it goes to WAT (white adipose tissue) found in centrally-located fat, ie toxic wheat-bellies (that Dr. Davis frequently refers to). PPAR-Delta again is responsible for regulating the 'switch' to preferred fuel metabolism!

"Fatty acid oxidation is the primary source of energy in the postnatal heart (67). Impaired fatty acid oxidation and a shift to reliance on glucose metabolism are hallmarks of myocardial diseases such as cardiac hypertrophy and congestive heart failure (67). As in skeletal muscle, PPARδ is a critical regulator of fatty acid oxidation in cardiac tissue. Cheng et al. showed that cardiac-specific deletion of PPARδ suppresses the expression of oxidative genes (68). This leads to impaired fatty acid oxidation and a reciprocal increase in glucose oxidation, along with fat accumulation in cardiomyocytes (68). Moreover, PPARδ-selective agonists increase fatty acid oxidation via the induction of oxidative genes in isolated neonatal as well as adult rat cardiomyocytes (69) (Table 1). The PPARδ-dependent maintenance of basal fatty acid oxidation is crucial for normal cardiac mechanics. PPARδ-null hearts are characterized by decreased rates of contraction and relaxation, increased left ventricular end-diastolic pressure, and decreased cardiac output, factors associated with the onset of cardiac failure (68). Indeed, mice with cardiac-specific deletion of PPARδ develop age-dependent cardiac lipotoxicity, cardiac hypertrophy, end-stage dilated cardiomyopathy, and decreased survival (68). The protective role of PPARδ in the heart has been confirmed by in vitro studies showing that PPARδ agonists attenuate phenylephrine-induced cardiac hypertrophy. While phenylephrine suppresses fatty acid oxidation in cardiomyocytes, concomitant activation of PPARδ reverses these effects (70). Although PPARδ may directly increase the transcription of fatty acid oxidative genes, at least 1 study suggests that effects could also be indirect. Planavila and colleagues showed that PPARδ interacts with and blocks NF-κB–mediated suppression of fatty acid oxidation in cardiomyocytes (71). PPARδ-dependent antagonism of NF-κB could be particularly important during sepsis, when endotoxins decrease cardiac fatty acid oxidation and initiate cardiac failure (71, 72)."
FIGURE. PPARδ: an inflammatory switch. In the absence of ligand, PPARδ-RXR heterodimers bind to consensus PPAR DNA response elements (PPREs) and repress target gene expression by recruiting corepressors and associated repressive proteins including B cell lymphoma-6 (BCL-6) (top). (VITAMIN A, RETINOIDS, CAROTENOIDS BIND RXR) Upon addition of PPARδ ligand (bottom left), PPARδ-RXR heterodimers undergo a conformational shift. This dismisses the corepressor complex, including BCL-6, in exchange for a complex of coactivator proteins and results in enhanced PPARδ target gene expression. BCL-6, an inflammatory suppressor protein, is thereby liberated to repress inflammatory gene expression.

Some natural nutrients and endogenous substances that bind or activate PPARdelta are listed below. What are the side effects of these receptor agonists? Vitality, strength and virility. No cancer, no heart disease, etc.
  • Fish oil (yeah my favorite) -- DHA, EPA -- n-3 PUFAs
  • Vitamin D, Vitamin A -- heterodimer with PPARs via VDR and RAR/RXR
  • Monounsaturated fatty acids (ie, olive oil)
  • Walnuts, Almonds (n-3 PUFAs, MUFAs)
  • Saturated fatty acids (our own adipose depots as burned with resistance training/exercise; consumed)
  • Eicosanoids -- Prostacyclin (PGI2), carbaprostacycline (cPGI2)
  • Protein -- indirectly activates PPARdelta via mTOR signalling
  • Physical movement -- especially resistance training with weights

  • Eat protein... MAKE PROTEIN, ie, muscles!

  • Dreyer HC, Drummond MJ, Pennings B, Fujita S, Glynn EL, Chinkes DL, Dhanani S, Volpi E, Rasmussen BB. Leucine-enriched essential amino acid and carbohydrate ingestion following resistance exercise enhances mTOR signaling and protein synthesis in human muscle. Am J Physiol Endocrinol Metab. 2008 Feb;294(2):E392-400. PMID: 18056791

  • Inactivity trains our muscles to degrade and die off. Eight hours of sedentary activity can lead to our most important muscle, the heart, to effectively atrophy. Whereas, use of muscles signals to the body to build m-o-r-e muscles. The resulting adaptations to movement are (1) muscle growth (2) increased synthesis of more mitochrondria (fuel-burning furnaces) (3) higher increases in glucose uptake and transporters for glucose (which thereby ameliorate insulin resistance).

    • Dreyer HC, Glynn EL, Lujan HL, Fry CS, DiCarlo SE, Rasmussen BB. Chronic paraplegia-induced muscle atrophy downregulates the mTOR/S6K1 signaling pathway. J Appl Physiol. 2008 Jan;104(1):27-33. Epub 2007 Sep 20. PMID: 17885021
    • Röckl KS, Witczak CA, Goodyear LJ. Signaling mechanisms in skeletal muscle: acute responses and chronic adaptations to exercise. IUBMB Life. 2008 Mar;60(3):145-53. Review. PMID: 18380005 Link to full article here (see below for 2 great figures).

      SUMMARY by Rockl et al: "Exercise is of critical importance for people with insulin resistance or diabetes. Our current understanding is that one of the many benefits of an acute bout of exercise is an insulin-independent increase in the glucose uptake capacities of skeletal muscle. Important chronic adaptations to exercise training are the increase of mitochondria and thus oxidative capacities in skeletal muscle, the transformation of muscle fiber types, and the increase in GLUT4 protein expression.
      Contractile activity and insulin are the most potent and physiologically relevant stimuli of glucose transport in skeletal muscle. While significant progress has been made in elucidating the insulin signaling pathway leading to GLUT4 translocation, identification of the signals mediating contraction-stimulated glucose transport has proved challenging. A growing body of data suggests that multiple signaling cascades mediate the metabolic effects of contraction. While the proximal signals leading to contraction- and insulin-stimulated glucose transport are clearly distinct, emerging studies have shown a reconnection or convergence of these signals at AS160.
      Exercise training induces an increase of oxidative capacity, fiber type changes, and elevated GLUT4 protein levels in skeletal muscle; adaptations which are of critical importance to lower free fatty acids, improve glucose uptake, and decrease the risk of insulin resistance and diabetes. Again, multiple signaling pathways appear to act synergistically to mediate adaptive responses to exercise training. In particular, AMPK and calcineurin have evolved as major candidates for mediating exercise-training adaptations. PGC-1 may be a point of convergence for both pathways. While considerable progress has been made in decoding molecular mechanisms around these molecules, more research will be needed to test their physiological role in skeletal muscle adaptations to exercise training. "

      Figure: Proposed model for the signaling pathways mediating insulin and contraction-induced skeletal muscle glucose transport. Insulin and contraction-mediated glucose transport occurs by translocation of glucose transporter 4 (GLUT4) from intracellular locations to the plasma membrane. Insulin binding leads to phosphorylation of the insulin receptor with subsequent activation of insulin receptor substrate 1/2 (IRS-1/2) and phosphatidylinositol 3-kinase (PI3-kinase). Downstream of PI3-kinase the protein kinases, Akt, which then regulates activation of Akt Substrate of 160 kD (AS160), and atypical protein kinase C (aPKC), have been identified to mediate insulin stimulated GLUT4 translocation. Contraction stimulated glucose uptake is mediated by multiple signaling pathways including aPKC, Ca2+/calmodulin-dependent protein kinase II (CaMKII), Ca2+/calmodulin-dependent protein kinase kinase (CaMKK), LKB1, and AMP-activated protein kinase (AMPK).

    Saturday, May 24, 2008

    Plaque, Plaque, and... More Plaque Reversal

    "Remodelling of alveolar bone involves interaction between osteoblasts and osteoclasts. Osteoblasts, under the influence of osteotropic hormones (vitamin D3, PTH and retinoic acid), produce MMPs which appear to function in the removal of soft tissue that precludes access of osteoclasts to the mineralized tissue surface.... Although there is strong evidence for the involvement of MMPs in the resorption of bone and in the inflammation-mediated destruction of periodontal tissues, the role of MMPs in the remodelling of mature soft connective tissues remains equivocal."

    Sodek J, Overall CM. Matrix metalloproteinases in periodontal tissue remodelling. Matrix Suppl. 1992;1:352-62. Review. PMID: 1480060


    Boyd LD, Lampi KJ. Importance of nutrition for optimum health of the periodontium. J Contemp Dent Pract. 2001 May 15;2(2):36-45. Review. PMID: 12167932 Link HERE *good review*


    Figure. Activation mechanisms of MMP-2. The full-length MMP-2 can be activated in two ways. Proteolytic activation of MMP-2 by MT1-MMP/TIMP or by other proteases occurs by removal of the autoinhibitory propeptide domain (left arrow) resulting in an active truncated MMP-2. The presence of oxidative stress (ONOO-) and cellular glutathione (GSH) causes the S-gluathiolation of the critical cysteine residue in the propeptide domain, disrupting its binding to the catalytic Zn2+ ion, resulting in an active full-length enzyme. MMP, matrix metalloproteinase; ONOO-, peroxynitrite; TIMP, tissue inhibitor of metalloproteinase. Chow AK, et al. Acute actions and novel targets of matrix metalloproteinases in the heart and vasculature. Br J Pharmacol. 2007 Sep;152(2):189-205.

    Recently we moved and lost our housekeepers. I've been in the double-dog dumps ever since... So to say the cleaning of the house has been neglected is a very grave understatement. Last week I devoted an inordinate amount of time scouring the calcium deposits off all the toilets in the house... it took so long so I had a long time to think. Why (??!) did I wait so long? Why did I let this thing go?? The work was so much harder and and tougher than had I just kept up with routine maintenance weekly. Right? (Also have spent time weighing the benefits of hiring professionals again) My girlfriends love using CLR (above ad) but I hesitate using such a strong cleaning solvent on the toilets not just for the environmental impact but also the corrosive effects on the pipes (not withstanding other effects such as melting my corneas and the first 2 layers of my skin -- rubber gloves are mandatory).

    As I was really getting into the scrubbing and facing the challenge of getting back an immaculate white and tidy bowl, I thought is this what my nazi-Dental Hygienist thinks every time she sees me as she sharpens her metal instruments for scraping tartar and plaque off the teeth? A few years ago I was diagnosed with gum disease with pockets of '4' and '5' and told that implants and antibiotic treatment et cetera might be required some day. When you have periodontal disease, extra cleanings (btw are NOT covered by insurance) and deep scaling/root planing (yes it's as nasty as it sounds) are required to control plaque with the hopes of reducing inflammation and further damage. Gum disease actually involves similar processes that atherosclerosis/heart disease involves, including destruction by excessive MMPs. On the surface of atherosclerotic plaques in our blood vessels, MMPs are found. Destabilization of plaque has been related to overactivity of MMPs. The above article demonstrates the value of vitamin D3 and vitamin A (retinoic acid) and PTH in ameliorating gum disease and correcting the balance between building (osteoblastic activity) and cutting (osteoclastic activity) of our mature gum soft tissues. Interestingly these agents, Vitamins D3 and A, also have incredible plaque-busting benefits in the Track Your Plaque program for CAD regression and eradication. Dr. Davis demonstrated the value of Vitamin D3 in shrinking plaque in coronary arterties and heart disease reversal.

    My gum disease now has reversed. I've attributed all the benefits to a low-inflammatory diet (ie rich in good oils, protein, veggies and low low carb), exercise, A-N-D vitamins D3, A and high dose EPA + DHA fish oil. At the end of sumer last year, surprisingly, my lab 25(OH)D3 was extremely low (after being in the sun daily for hours with the kids at the pool). Correction of vitamin D deficiency was one component of improving periodontal disease (obtaining blood levels of 50-60 ng/ml). Happily, at my last visit to the dentist, my gums were given a clean bill of health. Nearly all the pockets were '3's and a few '4's now. The '5's had disappeared and I was told I could return to a normal bi-annual cleaning schedule again (and no more out-of-pocket cleanings). The throbbing that I once felt in the gums are gone too.

    Other MMP inhibitors include Doxycline (part of the tetracycline family of drugs). It is a prescription drug which is used in the treatment of periodontal disease and gingival inflammation but has also demonstrated some value in atherosclerosis and preventing heart failure remodeling. PERIOSTAT is a brandname Doxycline indicated by the FDA for treatment of gum disease.
  • Tessone A, et al. Effect of matrix metalloproteinase inhibition by doxycycline on myocardial healing and remodeling after myocardial infarction. Cardiovasc Drugs Ther. 2005 Dec;19(6):383-90. PMID: 16435072
  • Chow AK, Cena J, Schulz R. Acute actions and novel targets of matrix metalloproteinases in the heart and vasculature. (see above Figure) Br J Pharmacol. 2007 Sep;152(2):189-205. Epub 2007 Jun 25. Review. PMID: 17592511

    I wish I could stick vitamin D in all my toilets everyday... *heh*
  • Dietrich T, et al. Association between serum concentrations of 25-hydroxyvitamin D and gingival inflammation. Am J Clin Nutr. 2005 Sep;82(3):575-80. PMID: 16155270

    Rickets -- a profound vitamin D deficiency condition which frequently involves signficant dental disease (because vitamin D plays a vital role in calcification of teeth and remodeling of soft gum tissues).
  • Chaussain-Miller C, et al. Dentin structure in familial hypophosphatemic rickets: benefits of vitamin D and phosphate treatment. Oral Dis. 2007 Sep;13(5):482-9. PMID: 17714351
  • Yamamoto T. Diagnosis of X-linked hypophosphatemic vitamin D resistant rickets.
    Acta Paediatr Jpn. 1997 Aug;39(4):499-502. Review. PMID: 9316300
  • Chaussain-Miller C, et al. Dental abnormalities in patients with familial hypophosphatemic vitamin D-resistant rickets: revention by early treatment with 1-hydroxyvitamin D. J Pediatr. 2003 Mar;142(3):324-31. PMID: 12640383

    Dental insurances allow one extra covered dental cleaning during pregnancy. Studies show that the pregnancy-state increases the risk of periodontal disease (likely secondary to cortisol, inflammation, insulin? vitamin D and EPA/DHA deficiency? I would presume). Prevention with an extra cleaning is therefore now advocated. Isn't that interesting? Pregnancy may significantly deplete vitamin D stores (unless replenished) -- in order to construct enough progesterone and estrogen which are also steroidal hormones for supporting the pregnant state. Both pregnancy and lactation also reduce the mother's stores of EPA+DHA in her brain and heart in order to supply the growing fetus/baby's brain and heart. Did you know that a baby's brain is 70% of its birth weight? And did you know that breastmilk is a rich source of 'fish oil' EPA + DHA !

    This researcher believes that maternal imprinting can affect CAD risk later in life. By not consuming enough good oils during conception and pregnancy, are we affecting our children later in life? He strongly believes fish oil may protect and even prevent CAD and diabetes in children when maternal EPA and DHA are adequately provided.
  • Das UN. A perinatal strategy to prevent coronary heart disease. Nutrition. 2003 Nov-Dec;19(11-12):1022-7. Review. PMID: 14624957

  • Cerná H, et al. Acta Univ Palacki Olomuc Fac Med. 1990;125:173-9. Periodontium and vitamin E and A in pregnancy.
    The evaluation of the clinical condition of periodontium by means of the epidemiological indexes and the level of oral hygiene in two weeks intervals in the course of physiological pregnancy in 39 women in good general health revealed the maximum of inflammatory changes of periodontium in the 8th month of pregnancy with the amelioration shortly before delivery. Simultaneous follow-up of the physiological levels of vitamin E and A in four weeks intervals showed the decline of the mean levels of both vitamins in the course of the 8th month and their marked elevation shortly before delivery; therefore remains questionable, if this elevation reaching over their physiological range, contributes to the amelioration of the condition of periodontium observed at the same time. PMID: 2150274

    Phenytoin is a drug that increases the liver metabolism of certain drugs and hormones, including Vitamin D and Vitamin A. Seizure and other individuals taking Phenytoin can be at risk not only for osteoporosis but also gum disease (and heart disease and many over conditions) due to subsequently low vitamin D levels. (Isotretinoin is a synthetic vitamin A)
  • Norris JF, Cunliffe WJ. Phenytoin-induced gum hypertrophy improved by isotretinoin. Int J Dermatol. 1987 Nov;26(9):602-3. No abstract available. PMID: 2965113
  • Lucchesi JA, et al. Severe phenytoin-induced gingival enlargement associated with periodontitis. Gen Dent. 2008 Mar-Apr;56(2):199-203; quiz 204-5, 224. PMID: 18348382
  • Hall EE. Prevention and treatment considerations in patients with drug-induced gingival enlargement. Curr Opin Periodontol. 1997;4:59-63. Review. PMID: 9655022
  • Sobaniec H, et al. Antioxidant activity of blood serum and saliva in patients with periodontal disease treated due to epilepsy. Adv Med Sci. 2007;52 Suppl 1:204-6. PMID: 18229666

    Vitamin A is also helpful for reversing gum disease in a condition called Papilon-Lefevre syndrome.
  • Nazzaro V, et al. Papillon-Lefèvre syndrome. Ultrastructural study and successful treatment with acitretin. Arch Dermatol. 1988 Apr;124(4):533-9. PMID: 2965550

    When I think about inflammation and the crucial role fish oil plays in maintaining healthy hearts and minds.... I am not shocked to find out it also regulates healthy gums and oral health. Friends on the TYP forum on the other hand will be shocked that I've reduced my dose of fish oil (slightly) since our family started drinking grass-raised cow milk which is rich in EPA+DHA, CLA, vitamins A D3 E and K2. I love fish oil for all its amazing benefits. Here is more evidence for its healing properties on gingival inflammation (and the hypothesized relationship with vascular inflammation).
  • Fish oil reduces tooth loss mainly through its anti-inflammatory effects?
    Hamazaki K, et al. Med Hypotheses. 2006;67(4):868-70.
    Competing at several steps of arachidonic acid metabolism, n-3 fatty acids reduce production of highly active prostaglandins and leukotrienes and exert anti-inflammatory effects. They are also experimentally shown to be anti-osteoporotic. Periodontitis is responsible for most tooth loss in adult populations. If enough n-3 fatty acids are provided, periodontitis with alveolar bone resorption may be controlled, and tooth loss may be prevented. In fact, n-3 fatty acid administration lowered prostaglandin E(2) production, tooth movement and alveolar bone resorption in animal experiments. Aggression, which may be related with tooth loss, was also controlled with fish oil. Our cross-sectional data supported our hypothesis. We recruited 256 men (22-59 y of age) and 95 women (22-66 y), counted the numbers of their remaining teeth, and analyzed the fatty acid composition of the total phospholipid fraction of RBCs. The beta-coefficient of the numbers of remaining teeth and EPA concentrations in the fraction was 0.89 (per 1% EPA, p=0.007) after adjustment for 9 possible confounding factors. Long-term intervention studies with fish oil planned in the future should be able to test our hypothesis by just adding another very simple endpoint in those studies: tooth loss during the intervention period. This hypothesis may explain the linkage between periodontitis/tooth loss and coronary heart disease. PMID: 16759817

  • Campan P, et al. [Polyunsaturated omega-3 fatty acids in the treatment of experimental human gingivitis] Bull Group Int Rech Sci Stomatol Odontol. 1996 Feb-Mar;39(1-2):25-31. French. PMID: 8720373
  • Kesavalu L, et al. Omega-3 fatty acid effect on alveolar bone loss in rats. J Dent Res. 2006 Jul;85(7):648-52. PMID: 16798867
  • Kesavalu L, et al. Omega-3 fatty acid regulates inflammatory cytokine/mediator messenger RNA expression in Porphyromonas gingivalis-induced experimental periodontal disease. Oral Microbiol Immunol. 2007 Aug;22(4):232-9. PMID: 17600534
  • Requirand P, et al. Serum fatty acid imbalance in bone loss: example with periodontal disease. Clin Nutr. 2000 Aug;19(4):271-6. PMID: 10952799
  • Iwami-Morimoto Y, Yamaguchi K, Tanne K. Influence of dietary n-3 polyunsaturated fatty acid on experimental tooth movement in rats. Angle Orthod. 1999 Aug;69(4):365-71. PMID: 10456605

    Nutritional factors play the same important roles in parallel organs in our body. Perhaps proper vitamins/food and fish oil everyday will not only keep the doctor away...

    But also my nazi-hygienist! :)

    If only the same were true for all other types of housekeeping.

    (Thanks go out to Mr.California for his super-RICH ideas. You deserve an 'S' emblazoned on your chest for sharing your fascinating cardiovascular-related thoughts and insights.)

  • Thursday, May 15, 2008

    What To Do After You've Lost 50 # ? Get Into My Genes...

    What To Do After You've Lost 50 lbs:
    1. Get rid of your larger-sized jeans -- donate 'em, burn 'em, give them away, t-h-r-o-w them away so you don't get any ideas
    2. Buy new hot jeans, preferable anything that makes you look hotter
    3. Get rid of your larger-sized undies b/c they will peak out of your sexy new(low rise) jeans.
    4. Welcome the customer service you'll get (sad but true) -- the better you look the better service (even though you're the s-a-m-e cranky consumer).
    5. The better the service, the bigger the spending. Get a larger wallet!

    About 5yrs ago I started on a 'health' kick which started when I couldn't fit into my size 10-12 jeans. Everyone reaches their own personal 'rock bottom' at some point which starts the process of life-altering new change. My rock bottom occurred when my bottom couldn't fit. *sigh* Wish I could say it was for improving my 'fitness' or 'golf' or 'longevity' or 'primary coronary prevention'. Nope.

    You wanna get into my genes?

    After losing 50 lbs (low carb, working out, yoga, eliminating juice/cereal/rice) and achieving the ultimately best health ever, I would say my genes ROCK now. Can we alter our genes and genetics? (Clinton was once clobbered for saying he changed his 'genes' and after making adjustments to his diet and weight after his multiple-vessel CABG .... we wondered what (??!) was he was talking about) *heh*

    It certainly is possible to optimize and out-maneuver genetic polymorphisms (and other DNA curses). With a semi-Paleo diet, inadvertently fasting intermittently (cheating with chocolate and coffee), exercise (both low and high intensity), the weight went from originally 158 to finally 108 lbs... (115 lbs now after growing 7 lbs of muscle/mammaries/hair ... they're real... and spectacular... J/K (!!)... miss my Seinfeld). My BMI is 19.4 (size 1). I started at 38% body fat (wow -- more than 1/3 of the initial weight) and now I'd estimate 19-22%. Was it hard? Let me tell you... it wasn't always easy. But it wasn't difficult once the process started. Like a rock rolling down a hill. At some point, natural laws of gravity kick in -- with big enough kicks(and other physics, such as smaller masses require shopping for smaller jeans). Psychologists say that change takes 2 weeks to occur and be reinforced.

    Randomness in workouts helps me -- mixing up the intensity and varying the lengths. Boredom can't set in when the routine is constantly changing, setting new bars of achievement (instead of 2 miles, 4 miles), finding friends to join in the fun, or attending classes where you can share camaraderie (and accountability).

    French culture have taught us yet another lesson (other than croissants, butter, wine, cheese and other good foods can be good for us). By consuming the right balance of foods and right portions for our specific genetics, we can extend health, longevity, and vitality to the maximum. Make the most of the interplay between personal genetics and diet. As certain genes can be turned on for optimization of health, many genes can be down-regulated and shut OFF to stop and control chronic diseases.

    As Hippocrates once said "Let thy food be thy medicine, and thy medicine thy food."

    No pain-au-chocolat, no gain!

    (Food was probably high-carb 50-80% of daily calories-- the context would not apply necessarily to TYP-ers and therefore dietary fat effects may not extrapolate out)Features of the metabolic syndrome (MetSyn) are modulated by an interaction between the peroxisome proliferator-activated receptor-delta -87T>C polymorphism and dietary fat in French-Canadians. Robitaille J, et al. J Obes (Lond). 2007 Mar;31(3):411-7. (More on PPAR-delta later... what a fascinating receptor)

    OBJECTIVE: We verified whether genetic variants in this gene are associated with the MS and whether dietary fatty acids interact with the -87TC polymorphism.

    METHODS: By direct sequencing, we identified 15 variants in the PPAR-delta gene and analyses were pursued with the -87TC polymorphism for 340 subjects.

    RESULTS: Metabolic variables were comparable among each genotype group. The -87TC polymorphism, fat intake and the interaction accounted, respectively for 2.2, 1.9 and 1.5% of the variance in high-density lipoprotein cholesterol (HDL-C) levels (P less than 0.05) (age, sex and energy intake were included into the model). The total cholesterol/HDL-C ratio was also modulated by a gene-diet interaction and by the -87TC polymorphism (P less than0.05). No gene-diet interaction effects were observed for other features of the MS. The age- and sex-adjusted odds ratio (OR) of exhibiting three or more features of the MS when carrying the -87C allele was 0.62 (P=0.04) compared to -87T/T. However, in subjects consuming less than 34.4% of energy from fat (median of fat consumption), the OR in carriers of the -87C allele was of 0.42 (P=0.008).

    CONCLUSION: These data suggest that the PPAR-delta -87TC polymorphism may be associated with a lower risk to exhibit the MS and this association is influenced by dietary fat intake.The metabolic syndrome (MS) is influenced by genetic and environmental factors. Peroxisome proliferator-activated receptor delta (PPAR-delta), a transcription factor involved in lipid metabolism, is a candidate gene for the MS. PMID: 16953259

    A certain genetic type (polymorphism) determines whether saturated fat increases apo B (and Metabolic Syndrome and thus small dense atherogenic LDL and plaque-progression) or protects against elevated apo B (et cetera). I wish I could get into my genes... but I would bet that my genes exhibit the apo B/MetSyn/atherogenic type... like the great majority of the global human population (insulin resistant with age, sedentary lifestyle, and excessive carb intake). The A94 type is impressive (A++) but unfortunately my genes probably wouldn't be so lucky. I wish I had A++ genes... but I more than make it up with A++ physical activity and food. Robitaille J, et al. Mol Genet Metab. 2004 Aug;82(4):296-303.

    Plasma concentrations of apolipoprotein B are modulated by a gene--diet interaction effect between the LFABP T94A polymorphism and dietary fat intake in French-Canadian men.
    Hyperapobetalipoproteinemia is a common feature of the metabolic syndrome and could result from the interaction between genetic and dietary factors. The objective of this study was to verify whether dietary fat intake interacts with the T94A polymorphism of the liver fatty acid-binding protein (LFABP) gene to modulate plasma apolipoprotein (apo) B levels. Dietary fat and saturated fat intakes were obtained by a dietitian-administered food frequency questionnaire and the LFABP T94A genotype was determined by a PCR-RFLP based method in 623 French-Canadian men recruited through the Chicoutimi Lipid Clinic (279 T94/T94, 285 T94/A94, and 59 A94/A94). The LFABP T94A polymorphism was not associated with plasma apo B levels when fat intake was not taken into consideration. However, in a model including the polymorphism, fat intake expressed as a percentage of total energy intake, the interaction term and covariates, the variance in apo B concentrations was partly explained by the LFABP T94A polymorphism (5.24%, p = 0.01) and by the LFABP T94A*fat interaction (6.25%, p = 0.005). Results were similar when saturated fat replaced fat intake in the model (4.49%, p = 0.02 for LFABP T94A and 6.43%, p = 0.004 for the interaction). Moreover, in men consuming more than 30% of energy from fat, the odds ratio for having plasma apo B levels above 1.04 g/L for A94 carriers was of 0.40 (p = 0.02) compared to T94/T94 homozygotes. Results were similar for carriers of the A94 allele consuming more than 10% of energy from saturated fat (OR: 0.32, p = 0.005).

    In conclusion, T94/T94 exhibit higher apo B levels whereas carriers of the A94 allele seem to be protected against high apo B levels when consuming a high fat and saturated fat diet. These findings reinforce the importance to take into account gene-diet interactions in the prevention and management of the metabolic syndrome. PMID: 15308127

    Monday, May 5, 2008

    Bourne Again

    Extreme Ways by Moby
    Bourne Identity
    Courtesy of

    Extreme ways may have eventually fallen apart for Mr. Jason Bourne until ultimately he reclaimed his life and identity. Exercising to extreme degrees can actually produce immense gains in fitness and cardiovascular benefits. Some proponents believe our bodies were built for extreme random bursts of energetic anaerobic output as evolutionary-related adaptations to hunting and escaping predators.

    Forging elite health is what WAPF and the Paleo diet are all about. The effects of the program are extraordinary vitality, longevity and health. Cancer prevention, hypertension normalization, and diabetes amelioration are additional side benefits.

    Crossfit is a new strength/conditioning program I'm trying. It's based on military training for special ops, police academies and even grandmas (according to their advert). Did you know Tiger Woods is using NAVY Seal training to help his awesome game?? To be sure, CF is far different from any 'gym' program out there. In fact it's kicking my a** right now. The Newbie torture routines include pull-ups (I can't even do one), jumping on blocks, lifting 80#barbells (I can't even lift my 50 lb kids!), and many many many squats. Blisters on my hand are raw and popping... Both my abs and a** (!!) hurt. Even my armpits ache (!!).

    In a relatively short period, however, I feel swiftly-strong... so... ghetto-sharp...

    So... La Femme Nikita... so... Bond Agent 007...

    I'm... BOURNE-AGAIN ! *wink*

    How can random interval training with high intensity movements benefit the heart and vasculature? This recent study shows how high intensity interval sprints are just as good as high volume endurance training on increasing popliteal artery dilation and distensibility. A randomized controlled trial using high intensity progressive weight lifting in diabetes Type 2 individuals also revealed incredible benefits on improving insulin sensitivity and all the hallmarks of metabolic syndrome (MetSyn). Another study demonstrated improvement in relaxation of heart with a high intensity exercise program in a short 10-day period of time. They showed it is possible to reverse early parameters of diastolic dysfunction (heart failure) in obese MetSyn age 39-60 with simple movements like one hour of walking on the treadmill at 70-75% of max effort.

    Whether it's playing catch with your kid, Curves, or Crossfit, embrace intensity and challenge your physical limits.

    If you have symptomatic or asymptomatic CAD, consult with your Cardiologist prior to starting an exercise program. Always start low and go slow to prevent injuries.

    Saturday, May 3, 2008

    Deliver Me

    FBI Agent Scully Tribute
    Deliver Me by Sarah Brightman
    No full video, here's alternative
    Awesome fan XF2 & leaked trailer
    Courtesy of

    X-Files 2 Movie is returning: July 25, 2008!! 'I Want To Believe' You can't handle the truth...

    Paranormal, supranormal, ab-normal....

    What is n-o-r-m-a-l these days? In America?

    Apparently according to the data in the latest report in Forbes magazine in Feb 2007 (so the data is probably worse now), America ranks 9th for being most 'obese'. They state that 74.1 % of Americans over the age of 15 years old are overweight.

    Studies are now pouring in showing obesity and carrying extra weight are causing early heart dysfunction in children, teenagers, young adults and adults. What is causing this metabolic derangement? High carbohydrate intake provokes hyperinsulinemia (elevated insulin levels). The more evident the features of metabolic syndrome, the more cardiac structure changes and abnormalities are being seen in the general population. This report from Poland (unfortunately only the abstract is in English) demonstrated the value of changing nutritional factors which not only improved obesity in children age 7-15 but also normalized lipoproteins: by reducing 'sugar, sweets, cereal foodstuffs and fat' (i.e., high glycemic c-a-r-b-o-h-y-d-r-a-t-e-s).
    • van Putte-Katier N, et al. Early Cardiac Abnormalities in Obese Children: Importance of Obesity Per Se Versus Associated Cardiovascular Risk Factors. Pediatr Res. 2008 Mar 26. PMID: 18391840
    • Sharpe JA, et al. Impact of obesity on diastolic function in subjects less than or = 16 years of age. Am J Cardiol. 2006 Sep 1;98(5):691-3. PMID: 16923463
    • Di Salvo G, et al. Abnormal myocardial deformation properties in obese, non-hypertensive children: an ambulatory blood pressure monitoring, standard echocardiographic, and strain rate imaging study.Eur Heart J. 2006 Nov;27(22):2689-95. PMID: 16905554
    • Kinik ST, Varan B, Yildirim SV, Tokel K. The effect of obesity on echocardiographic and metabolic parameters in childhood. J Pediatr Endocrinol Metab. 2006 Aug;19(8):1007-14. PMID: 16995586
    • Peterson LR, et al. Alterations in left ventricular structure and function in young healthy obese women: assessment by echocardiography and tissue Doppler imaging. J Am Coll Cardiol. 2004 Apr 21;43(8):1399-404. PMID: 15093874
    • Di Bello V, et al. Obesity cardiomyopathy: is it a reality? An ultrasonic tissue characterization study. J Am Soc Echocardiogr. 2006 Aug;19(8):1063-71. PMID: 16880104
    • Tumuklu MM, et al. Effect of obesity on left ventricular structure and myocardial systolic function: assessment by tissue Doppler imaging and strain/strain rate imaging. Echocardiography. 2007 Sep;24(8):802-9. PMID: 17767529
    • Grandi AM, et al. Obesity and left ventricular diastolic function: noninvasive study in normotensives and newly diagnosed never-treated hypertensives. Int J Obes Relat Metab Disord. 2000 Aug;24(8):954-8. PMID: 10951532
    • Goland S, et al. Cardiac abnormalities as a new manifestation of nonalcoholic fatty liver disease: echocardiographic and tissue Doppler imaging assessment. J Clin Gastroenterol. 2006 Nov-Dec;40(10):949-55. PMID: 17063117