Category Archives: Alzheimer’s Disease

Punicalagin and Pomegranate juice for Alzheimer’s disease and inflammatory conditions!

Save your brain! Drink Pomegranate juice!
Save your brain! Drink Pomegranate juice!

Polyphenols have been shown to exhibit neuroprotective effects suppress neuroinflammation and activate antioxidant mechanisms.

A polyphenol found in pomegranate fruit, punicalagin, inhibits neuroinflammation in LPS-activated rat primary microglia by suppressing the production of pro-inflammatory cytokines (TNF- and IL-6), and PGE2 after 24 h of stimulation with LPS.

Punicalagin, which is a polyphenol – a form of chemical compound found in pomegranate fruit, can inhibit inflammation in specialised brain cells known as microglia. This inflammation leads to the destruction of more and more brain cells, making the condition of Alzheimer’s sufferers progressively worse . Recent results suggest that punicalagin inhibits neuroinflammation in microglia through interference with NF-[kappa]B signalling.

It is recommended to consume juice products that are 100 per cent pomegranate, meaning that approximately 3.4 per cent will be punicalagin. Unfortunately, most of the anti-oxidant compounds are found in the outer skin of the pomegranate, not in the soft part of the fruit. Pomegranate may be useful in neuroinflammatory conditions other than Alzheimer’s disease, including cancer and Parkinson’s disease.

Bottom Line: EAT YOU pomegranates! Punicalagin is good for your brain. The juice is the best was to get the most of the phytonutrient. It’s role in reducing the risk of Alzheimer’s disease and other inflammatory conditions is still being evaluated, but seems very promising.

 

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Below is Nonsense relating to neuroinflammation, studies involving Punicalagin, and cytokines in the CNS:

Cytokines are polypeptides (proteins) that cause inflammation, immune activation, cellular differentiation, and death. They include interferons (INF) , tumor necrosis factor (TNF) , interleukins(IL) , chemokines, and growth factors. None of these are present to any degree in healthy tissues, but rather are induced by cell damage and tissue injury.

In the CNS, Tumor necrosis factor alpha (TNFa), Interleukin-1 (IL-1), and Transforming Growth Factor Beta (TGFb) are primarily the main cytokines. Each of these cytokines binds a specific receptor, which activates a process or signaling pathway, which include the NfkB and MAPK (mitogen activated protein kinase) pathways.

In the CNS, other cytokines include:

  1. IL-2
  2. IL-3
  3. IL-10
  4. Chemokines (fractalkine, IL-8, RANTES)
  5. Neuropoietic cytokines (IL-6, IL-11)

In a  very basic categorization, the pro-inflammatory cytokines are : IL-1, TNF-a, IL-6, and the anti-inflammatory cytokines are IL-1ra (IL-1 receptor antagonist), IL-10, and TGFb

It has been noted that TNFa and IL-1 increase in the brain prior to neuronal death, and there are increased cytokines in stroke. The presence of IL-6 and TNFa are found to be increased in areas of tissue injury and in tissues in which there were poor clinical outcomes.

Some cytokines are synergistic – i.e. IL1 and TNFa or INFg (gamma) cause neurotoxicity when they are around together. TNFa may have a dose-dependent neurotoxicity.

TNFa/IL-1 increase ischemic injury in the brain.

TGFb/IL-10/IL-1ra reduce neurological injury.

Chronic IL-6 expression is neurotoxic in mice.

Endogenous IL-1 expression induces neurodegeneration

IL-1ra inhibits brain damage caused by injury or excitotoxins.

If you inhibit IL-1ra, it has been found that ischemic damage occurs more frequently, hence IL-1ra is protective in the brain. If you block it, then you lose protection.

TGFB2 receptor (which binds protective TGFB), will induce damage in the brain by removing the protective TGFB, but having too much TGFb causes autoimmune encephalitis. Thus too much of a good thing can cause problems as well!

SO again :

IL-1 = neurodegenerative

TGF-b= neuroprotective

IL-10 = protective against injury

TNFa/IL-6 cause damage, but sometimes inhibit damage. It’s not always just they cytokines presence but WHEN they are present that counts. Il-1 and TNFa protect neurons if they are present BEFORE an injury, but if delivered at the time of injury, they cause destruction.

Different cells in the brain secrete cytokines. Glia, endothelial cells (lining of blood vessels),  microglia, and neurons express TNFa, which in turn induces IL-10 that feeds back to decrease TNFa production (negative feedback). There is a TNF alpha binding protein that influences and decreases TNFa and also fractalkins that cause microglia to secrete less TNFa as well.  All of these create feedbacks to limit cytokine production in complicated ways.

When damage occurs, the microglia (structural cells in the brain) first produce IL-1b(beta). The damage to cells causes extracelular ATP to be released and that activates P2X7 receptors that cause decreased intracellular potassium. This results in caspase 1 activation that causes the production of IL-1B, which in turn KILLS microglia and macrophages in the brain.

Also, during injury, TNFa release causes TGFb/IL6 expression.

Injury causes IL-1 to induce TNFa, IL-6, TGFb expression as well!

Infection and inflammation in the brain or periphery cause increased CNS cytokines and further inflammation. Hence peripheral inflammation affects CNS inflammation as well.

Excitotoxic amino acids also regulate cytokines after CNS injury as below:

Postsynaptic Density Protein 95 binds NMDA receptor subunit NR2 and Kainate recptor GLUR6 – which then phosphorylates C-JUn-N terminal kinase (JNK) and activates JUN. JUN promotes IL-1, IL-6, TNFa, INFa/g production.

Of note Cannabomids INHIBIT TNFa and IL-1 release from glial cells and are anti-inflammatory.

Neurons depend on glial cells for survival. Glial cells (astrocytes) produce neurotropins and growth factors (nerve growth factor (NGF), BDNF, GDNF)

Cytokines affect blood flow in the CNS as well indirectly. IL-1 induces neovasculariztion. IL-1 and TNFa damage the blood brain barrier and allow migration of molecules in and out of the CNS. They also cause NO (Nitric oxide) to be released, which is neurotoxic. They also upregulate adhesion molecules for leukocytes, that then enter the brain. What follows in vasogenic edema (swelling).

IL-1, IL-6, and TNFa also mediate fevers, endocrine reactions, and cardiovascular changes. This causes increased neuronal loss by alterations in blood flow and inflammation.

 

The COX-2 enzyme pathway and subsequent generation of prostaglandins play a significant role in neuroinflammation. mPGES-1 is the terminal enzyme for the biosynthesis of PGE2 (prostoglandin) during inflammation, and is functionally coupled with COX-2. This enzyme is markedly induced by pro-inflammatory stimuli and is down-regulated by antiinflammatory glucocorticoids  –   mPGES-1 inhibitors produced inhibition of PGE2 production

The transcription factor NF-B plays a crucial role in neuro-inflammation.

In resting cells, NF-B is sequestered in the cytoplasm by the inhibitory IB protein. When activated by a variety of stimuli that includes LPS (lipopolysacharride), IB is phosphorylated by IKK. Phosphorylated IB then undergoes ubiquitinisation and degradation . Dissociation and degradation of IB activates the translocation of NF-B subunit from the cytosol to the nucleus. The translocated subunit thereafter facilitates the transcription of several pro-inflammatory genes, including those encoding pro-inflammatory cytokines, and COX-2. Furthermore, microglial NF-B activation has been linked to brain damage

Punicalagin significantly inhibited LPS-induced NF-B signalling in microglia by suppressing the phosphorylation of IKK, IB and nuclear p65

Punicalagin produced a modest suppressive action on the phosphorylation of p38 and JNK MAPKs following LPS activation

Treatment with LPS in primary astrocytes triggered the synthesis of inflammatory cytokines, through MAPKs signalling pathways. Of particular interest is the role of p38, which has been shown to be a critical mediator of LPS-induced inflammation  .

It appears that the effects of punicalagin on neuroinflammation are mediated mainly through targeting NF-B signalling, while MAPKmediated actions are minimal. Studies have shown that the TLR-4-mediated TRAF- 6/IKK/NF-B pathway has been well established as a signalling pathway responsible for inflammatory responses.

In addition to NF-B activation, TLR-4 can also initiate MAPK signalling

Punicalagin inhibited TRAF-6 protein expression, suggesting that this compound may inhibit the IKK/IB/NF-B signalling pathway, as well as p38 and JNK MAPK via selective inhibition of TRAF-6

Treatment with LPS in primary astrocytes triggered the synthesis of inflammatory cytokines, through MAPKs signalling pathways.

 

Punicalagin inhibits neuroinflammation in LPS-activated rat primary microglia (1)  <–   punicalagin inhibited COX- 2 and mPGES-1 after 24 h of LPS stimulation, suggesting that punicalagin acts to reduce PGE2 production by interfering with both COX-2 and mPGES-1 enzymatic activities in LPS-activated microglia.

Graphics from NATURE –

Signal transduction through IL-1RI and TNFR1

MAP kinases and innate immunity - call

 

 

Xu, X., Yin, P., Wan, C., Chong, X. et al., Punicalagin inhibits inflammation in LPS-induced RAW264.7 macrophages via the suppression of TLR4-mediated MAPKs and NF-B activation. Inflammation 2014, 37, 956–965.  Punicalagin inhibits inflammation in LPS-induced RAW264.7 macrophages via the suppression of TLR4-mediated MAPKs and NF-B activation

Punicalagin Inhibits Inflammation in LPS-Induced RAW264 7 macrophages   <– punicalagin (25–100 M) suppressed NO, PGE2, TNF-, IL-6 and IL-1 production from LPS stimulated RAW 264.7 cells.

Winand, J., Schneider, Y. J., The anti-inflammatory effect of a pomegranate husk extract on inflamed adipocytes and macrophages cultivated independently, but not on the inflammatory vicious cycle between adipocytes and macrophages. Food Funct. 2014, 5, 310–318.  The anti-inflammatory effect of a pomegranate husk extract on inflamed adipocytes and macrophages cultivated independently, but not on the inflammatory vicious cycle between adipocytes and macrophage  <–Demonstrated the  inhibitory effects of punicalagin on TNF- and NO production in LPS-stimulated RAW 264.7 cells, as well as IL-6 production in LPS-stimulated 3T3-L1 adipocytes.

Nature and consequences of non-covalent interactions between flavonoids and macronutrients in food

The p38 MAPK inhibitors for the treatment of inflammatory diseases and cancer  <<–  The p38 MAPK signaling cascade is involved in various biological responses other than inflammation such as cell proliferation, differentiation, apoptosis and invasion. The p38 MAPK, originally referred as cytokine-suppressive anti-inflammatory drug binding protein (CSBP). p38 MAPK is activated by pro-inflammatory cytokines such as interleukins and TNF-α. Stimulation of receptors that initiate this cascade  include GPCR, cytokine receptors, Toll-like receptors, growth factor receptors, and receptors associated with environmental stress such as heat shock, radiation and ultraviolet light. p38 MAPK is activated by upstream MAPK kinases (MKK) p38 MAPK pathway plays a central role in the expression and activity of pro-inflammatory cytokines such as TNF-α, IL-1, IL-2, IL-6, IL-7, and IL-8 and plays a regulatory role in cell proliferation and differentiation in the immune system.   It also regulates the expression of several MMPs involved in inflammation such as MMP-2, MMP-9, and MMP-13.

 

p38 MAPK inhibitors have been shown to reduce LPS-induced TNF-α production (Pharmacological profile of SB 203580, a selective inhibitor of cytokine suppressive binding protein/p38 kinase, in animal models of arthritis, bone resorption, endotoxin shock and immune function.)

(CYTOKINES AND ACUTE neurodegenration)   <<- Brain inflammation has been implicated in the pathogenesis of neurodegeneration in common neurological diseases such as stroke and Alzheimer’s disease

 

b-Amyloid Fibrils Activate Parallel Mitogen-Activated Protein kinase pathways in microglia  < – Noted  that p38 MAPK was upregulated in the brains of a transgenic mouse model of Alzheimer’s disease.  Fibrillar forms of b-amyloid (Ab), which are the primary constituents of senile plaques, have been shown to activate tyrosine kinase-dependent signal transduction cascades, resulting in inflammatory responses in microglia.

There is involvement of p38 MAPK in cancer cell invasion. Of note,  p38α and p38β were found to play important roles in cell differentiation and invasion of several different cancer cells such as breast cancer, squamous carcinoma cell, colon cancer, and ovarian cancer

 

The Evolving Biology of Microglia in Alzheimer’s Disease

Cannabinoids and Neuroprotection in Global and Focal Cerebral ischemia  <–CANNABINOIDS inhibit IL-1 and TNFα expression and release from glia, and have anti-inflammatory and neuroprotective actions in vitro and in vivo

Common pathways of neuronal cell death have been identified in response to diverse insults, such as ischaemia, trauma or excitotoxicity. These include early disruption of ion homeostasis, excessive neuronal activation, seizures and spreading depression, massive release and impaired uptake of neurotransmitters such as glutamate, intracellular entry of Ca2+, and release of nitric oxide and free radicals. More recently, further factors have been identified, including activation of genes that initiate or execute apoptosis, and the influence of glial and endothelial cells, extracellular matrix and invading immune cells. There is evidence that specific cytokines can act at most, if not all, of these steps, and probably have multiple actions on several cells or systems involved in neurodegeneration.

Increased expression of p38 MAPK and extracellular-signal-regulated kinase (ERK) has been found in ischaemic brain tissue after MCAo. Selective inhibitors of these pathways markedly reduce the ischemic injury in rodents. TNFR1 and TNFR2 (Tumor necrosis factor receptors) belong to the low-affinity neurotrophin receptor gene superfamily. TNFα elicits its biological effects on multiple cell types in the CNS through these receptors.

TGFβ- mediated signalling is also regulated through crosstalk with other signal transduction pathways, including MAPK.

So, IL-1ra, or a small molecule antagonist of IL-1 receptors, might be beneficial in acute neurodegenerative conditions. Studies are currently evaluating this.

 

 

 

 

 

Relton, J. K. & Rothwell, N. J. Interleukin-1 receptor antagonist inhibits ischaemic and excitotoxic neuronal damage in the rat. Brain Res. Bull. 29, 243–246 (1992). The first study to report that inhibition of endogenous IL-1 limits neuronal death induced by cerebral ischaemia or excitotoxicity in vivo.

Prehn, J. H., Backhauss, C. & Krieglstein, J. Transforming growth factor-β 1 prevents glutamate neurotoxicity in rat neocortical cultures and protects mouse neocortex from ischemic injury in vivo. J. Cereb. Blood Flow Metab. 13, 521–525 (1993). An early study showing neuroprotective effects of TGFβ in vivo against cerebral ischaemia, and in vitro against glu

Chao, C. C., Hu, S., Ehrlich, L. & Peterson, P. K. Interleukin-1 and tumor necrosis factor-α synergistically mediate neurotoxicity: involvement of nitric oxide and of N-methylD-aspartate receptors. Brain. Behav. Immun. 9, 355–365 (1995). An early study showing interactions between cytokines to influence neuronal death in vitro, using human fetal brain cell cultures composed of neurons and glia.

Nawashiro, H., Martin, D. & Hallenbeck, J. M. Inhibition of tumor necrosis factor and amelioration of brain infarction in mice. J. Cereb. Blood Flow Metab. 17, 229–232 (1996). An early study indicating that endogenous TNFα mediates ischaemic brain damage in vivo. TNFbinding protein — a naturally occurring inhibitor of TNF — reduced damage caused by focal cerebral ischaemia in mice.

Scherbel, U. et al. Differential acute and chronic responses of tumor necrosis factor-deficient mice to experimental brain injury. Proc. Natl Acad. Sci. USA 96, 8721–8726 (1999). This study might provide an explanation for seemingly conflicting reports indicating that endogenous TNFα is either neurotoxic (based largely on acute interventions) or neuroprotective (based largely on stadies on genetically modified animals). It reports that functional outcomes in TNFα-null mice were improved early after brain injury compared with wild type mice, but TNFα-null mice showed permanent deficits and reduced recovery.

Ferrari, D., Chiozzi, P., Falzoni, S., Hanau, S. & Di Virgilio, F. Purinergic modulation of interleukin-1β release from microglial cells stimulated with bacterial endotoxin. J. Exp. Med. 185, 579–582 (1997). An early study showing that IL-1β is released from microglia by activation of purinergic, P2X7 receptors. Bacterial LPS is required for activation of microglial IL-1β expression, whereas ATP induced cleavage and release.

Ohtsuki, T., Ruetzler, C. A., Tasaki, K. & Hallenbeck, J. M. Interleukin-1 mediates induction of tolerance to global ischemia in gerbil hippocampal CA1 neurons. J. Cereb. Blood Flow Metab. 16, 1137–1142 (1996). The first demonstration that endogenous IL-1 can mediate ischaemic tolerance. Pre-treatment of gerbils three days before global ischaemia reduced brain injury. IL-1 was induced by a brief period of ‘preconditionary’ ischaemia.

Carrié, A. et al. A new member of the IL-1 receptor family highly expressed in hippocampus and involved in X-linked mental retardation. Nature Genet. 23, 25–31 (1999). A direct link between one of the recently identified members of the IL-1/Toll receptor family in brain function. Cognitive function in patients with X-linked mental retardation is strongly associated with a nonsense mutation in a gene identified as IL-1-receptor-like protein (IL-1R AcPL).

Venters, H. D. et al. A new mechanism of neurodegeneration: a proinflammatory cytokine inhibits receptor signaling by a survival peptide. Proc. Natl Acad. Sci. USA 96, 9879–9884 (1999). This study provided a potential explanation for indirect effects of the proinflammatory cytokine TNFα on neuronal survival through modification of the signalling pathway of a protective growth factor, IGF. This mechanism might apply to other neurotoxic cytokines.

Loddick, S. A., MacKenzie, A. & Rothwell, N. J. An ICE inhibitor, z-VAD-DCB attenuates ischaemic brain damage in the rat. Neuroreport 7, 1465–1468 (1996). The first study reporting that inhibition of caspase activity protects against neuronal death (ischaemic brain damage) in vivo

Legos, J. J. et al. SB 239063, a novel p38 inhibitor, attenuates early neuronal injury following ischemia. Brain Res. 892, 70–77 (2001). The first study to show that selective inhibition of p38 MAPK, which is involved in IL-1 and TNFα signalling,

Troy, C. M., Stefanis, L., Prochiantz, A., Greene, L. A. & Shelanski, M. L. The contrasting roles of ICE family proteases and interleukin-1β in apoptosis induced by trophic factor withdrawal and by copper/zinc superoxide dismutase down-regulation. Proc. Natl Acad. Sci. USA 93, 5635–5640 (1996). An early study reporting the contribution of ICE (caspase 1) to apoptosis in a neuronal cell line (PC12 cells) and indicating that ICE acts through modification of superoxide dismutase 1.

Giulian, D., Woodward, J., Young, D. G., Krebs, J. F. & Lachman, L. B. Interleukin-1 injected into mammalian brain stimulates astrogliosis and neovascularisation. J. Neurosci. 8, 2485–2490 (1988). One of the first reports of IL-1 actions on nerve cells that might be relevant to neurodegeneration and repair

 

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Insane Medicine – Blood Markers for Alzheimer’s Disease

  • A recent paper listed below studied the presence of autolysosomal proteins (from nerve tissue exosomes) in the blood stream and found a very high correlation with the eventual appearance of Alzheimer’s disease some ten years before it is detectable clinically.
  • Cathepsin D, LAMP-1 (lysosome-associated membrane protein 1), and ubiquitinylated protein were higher in patients who developed Alzheimer’s disease whereas Heat-Shock protein 70 was lower.
  • These markers confirm neuronal lysozomal dysfunction years in advance of Alzheimers and these markers may be used as biomarkers of disease.
  • Altered lysosomal proteins in neural-derived plasma exosomes in preclinical Alzheimer disease
  • Neurology. 2015 Jun 10.

Insane Medicine – Inflammation as a cause of psychiatric conditions!

 

 

 

 

Clustering of Depression and Inflammation in Adolescents Previously Exposed to Childhood Adversity

http://www.sobp.org/files/public/BPS%20Press%20Release_Miller%20and%20Cole_FINAL.pdf   <<< Childhood Adversity Increases Risk for Depression and Chronic Inflammation

Insane Medicine – Lowering Dementia Risk

Dementia
Dementia

Research is demonstrating that treating multiple risk factors for dementia results in better outcomes than treating each factor individually. Risk factors include:

  1. Poor nutrition
  2. obesity’smoking
  3. physical inactivity
  4. cardiovascular risks
  5. depression
  6. social isolation
  7. lack of mental stimulation

Strategies to help deal with these risks have been shown to help improve cognitive performance. Just treating single variables such as high blood pressure or lack of exercise has less effect than hitting multiple factors at once. A study in Lancet Neurology (August 2014) revealed that one-third of Alzheimer’s Disease (AD) cases are attributable to modifiable factors and thus AD may be reduced in prevalence by improved education , treatment of depression, and management of vascular risk factors such as physical inactivity, smoking, hypertension, obesity, and diabetes.

  • Get regular exercise: this reduces stress, improves blood flow to the brain, strengthens connection of neurons in the brain, improves medical health and balance, thus reducing falls. The goal is 30 minutes of aerobic activity five times a week (walking, dancing, biking as examples) and strength training twice a week.
  • Challenge your brain: Demanding brain activities utilizing different aspects of your intellect help protect against cognitive decline, making your mind more efficient and able to focus. So expose yourself to new ideas and challenges mentally, so that you can maintain your memory skills and concentration abilities. Things like cross-word puzzles, checkers or cards help build up your brain as do math problems. Research shows that staying intellectually engaged may prevent AD. These types of brain challenges add to your cognitive reserve. Social interaction also plays a role in preventing cognitive decline. It has been found that those who play more games or puzzles were more likely to perform better on test of memory, learning, and information processing. They also have greater brain volume in areas associated with memory. Mental workouts enhance brain blood flow and promote cell growth, stronger neuron connections, and keep the brain efficient. It makes the brain less sensitive to trauma such as drugs, stroke, or disease. The internet has resources to help:  http://brainworkshop.sourceforge.net/  or http://sporcle.com/  or http://syvum.com/teasers/  or http://www.braingle.com/  or http://www.billsgames.com/brain-teasers/   So consider crossword puzzles, jigsaw puzzles, word searches, math problems, an brainteasers to exercise your mind!
  • Treat mental illness, especially depression: Sadness, hopelessness, and lack of energy may signal depression. Depression is associated with a high risk of cognitive decline. See your doctor to help get treatment.
  • Eat a healthy diet: Eat complex carbohydrates such as whole grains, legumes, fruits, and vegetables. Avoid sodas, sweets, and excess sugars. Protein is essential for growth and cell maintenance, so consider lean meats, fish, poultry, eggs, low fat dairy,  nuts, and beans. Chose healthy fats such as omega-3 fatty acids found in flaxseed oil, fish, and nuts. Monounsaturated fats are also healthful and is present in olive and canola oils. Polyunsaturated fats from corn, safflower, and sunflower seeds are fine as well. Avoid trans-fats. Remember to include your micronutrients and phytochemicals (found in plant sources).
  • Treat cardiovascular risks: Stop smoking, lose weight, be physically active, treat high blood pressure and diabetes, take your prescribed medications.

Avoid Trans-fats in your diet. It is found in many junk foods, especially fast foods, processed foods, baked goods, margarine, and other sources. These products and trans-fats perform about 10% worse on cognitive tests than those who consumed minimal amounts. Trans-fats promote oxidative stress and damage the memory center of the brain, the hippocampus.

Magnesium is essential for brain functioning. It is found in green leafy vegetables, whole grains, nuts, legumes, and hard water. Magnesium helps in energy production, needed especially in the brain. It helps in the formation and release of neurotransmitters as well as functioning of connections in the brain (synapses) to process new information. Studies in Molecular Brain (September 2014) demonstrated that magnesium L-threonate (MgT) supplementation prevented memory decline and prevented synapse loss in mice prone to AD. It also reduced the deposition of beta-amyloid protein in the brain (a cause of AD) Risk factors for magnesium depletion include chronic alcoholism, diabetes, excessive coffee intake, inflammatory bowel disease such as Chrone’s disease, diuretic intake, liver and kidney disease,  and excessive soda and salt intake.The RDA is 400 mg a day – http://ods.od.nih.gov/factsheets/Magnesium-HealthProfessional/  This link points to sources of magnesium for your diet. Foods included are Almonds, spinach, cashews, peanuts, shredded wheat cereal, soy milk, black beans, whole wheat bread, avocado, baked potato, brown rice, plain yogurt, and others.

This sounds dumb but avoid head injury – it has been shown that older adults who have a head injury are at higher risk of dementia, especially over the age of 65. The main reason for these injuries are falls, many of which are preventable and may be due to deconditioning and weakness from lack of exercise. Remember that exercise increases strength and balance.

Remember to not be anxious over your health – don’t become a hypochondriac. Maintain your health through proper eating, exercise, risk management of cardiovascular problems (high blood pressure, high cholesterol, smoking cessation), taking your prescribed medications, and regular physician check-ups will maximize your health. Don’t get preoccupied with health matters and fears of disease such that they interfere with your daily activities and enjoyments in life. Keep yourself busy and distracted by learning new tasks and volunteering. Consider meditation, relaxing your body and mind, concentrating on the present moment. Exercise your body to reduce stress and reduce your anxiety. This will build your physical strength and increase your feelings of well-being. Keep your head up with positive feeling and be grateful for the good things in your life and those things you can control. Don’t stress out!!

 

 

 

Insane Medicine – Dietary Review!

I wanted to generalize some overall health information in this particular blog and incorporate items that are important for increasing successful strategies for aging and maintaining your health.

  • Remember that circulation is important in your body because it provides energy and sustains life in the various tissues. Regular exercise is a way to keep your body maximally conditioned. Your circulation delvers oxygen and nutrients to your body and at the same time allows toxins to be removed as it passes through the liver, kidney, and lymph systems. So be certain to keep moving and exercise to maximize your health.
  • Eat more plant foods. As a result of doing this, you take in less fat and will increase your fiber intake. This allows more protecting antioxidants to be incorporated into your body. Ingesting more fiber allows for better waste removal, and less fat intake results in a decreased tendency for your blood to thicken and clot, thus decreasing cardiovascular risk. The large amount of protecting agents in plant-based diets results in less inflammation in the body and less cellular damage.
  • Choose plant foods with strong flavors and with bright colors. Have a healthy fat focus in your diet. Chose your beverages you drink wisely, in other words, stop drinking sodas! Try your best to allow your stomach to be empty  and have ‘hunger pains’ for at least two thirty minute periods each day.
  • Remember that the body evolved in a world where salt, sugar, and fat were scarce and are like addictive drugs. Be careful to avoid choosing processed foods when possible and not adding salt and sugar to your meals. Avoid sodas ( which are high in sugar content)! Even noncaloric beverages may be increasing our desire for sweet food and spurring increasing rates of obesity.
  • Fructose in our foods has been a source of increasing weight gain in our society. Fructose and glucose (both sugars) have a differential effect on the brain. Glucose will reduce activation of brain regions that are involved in appetite, motivation, and reward and will increase our sense of satiety and decrease our food seeking behavior. Fructose does not do this. It is sweet, but it makes us want more! Corn sweeteners (fructose) have correlated with rising obesity.
  • Plant-based foods give us phytochemicals which act as protectors. Plant-based foods give smell, taste, and fragrance to our diet. They have an antioxidant effect. Kale, cabbage, broccoli, and  arugula have a sulfur based mustard taste that increase detoxification enzymes in the body. You should get 5-9 servings of colorful, flavorful vegetables in your diet each day – five servings for smaller people and at least nine servings if you are a big person. How much is a serving for vegetables? One-half cup cut up is equal to a serving, in general, for vegetables (for raw spinach, a whole cup is equal to a serving)
  • So again – look for colorful vegetables, as they have higher levels of phytochemicals in them, For example, zucchini has a green outside but mostly colorless interior, and therefore is a poorer choice of a vegetable. Instead, go for the carrots, spinach, broccoli, and yellow squash as options, since they have more color to them and therefore more protective phytonutrients! You will find higher levels of Vitamin A in deep orange vegetables such as carrots. The carotenoids and retinol in these vegetables impart the orange coloring and give the protective qualities of these vegetables.  Cruciferous vegetables have a big, strong flavor with sulfur components. They have powerful antioxidants in them and include arugula, broccoli, brussel sprouts, cauliflower, kale, kholorabi, radish, rutabaga, and turnips. Citrus fruits are high in Vitamin C, which helps fight infection. They also have an antihistamine/anti-allergic effect as well as anti-oxidant effect, which protects cell membranes and DNA in the body from oxidative damage. Vitamin C is important in the production of collagen component of connective tissues such as tendons and ligaments.
  • Eating up to nine servings a day of vegetables was associated with 24% less obesity in one study. Why? Because you eat less of other fatty foods.
  • Fiber rich foods  are very important in the diet. Vegetables, fruits, beans, whole grains are all rich sources of protective nutrients and phytochemicals and have a lower glycemic load as well. Eating foods with high fiber content results in less obesity since people who consume high-fiber foods feel more full. Likewise, higher fiber meals cause increase transit through the gut and decrease carcinogen exposure. This results in less colon cancer risk! Soluble fiber decreases cholesterol levels while fibrous food will increase the amount of protective gut bacteria.
  • We will be discussing the gut biome over time in this blog. Your gut has a population of bacteria that live and thrive but also help us maintain homeostasis. Alterations in the gut biome (bacterial population) can result in inflammation and disease. Immune compromise can occur if the gut biome is altered or destroyed. It turns out that soluble fiber is a food source for these necessary gut bacteria to remain healthy, and hence us as well.
  • We need 25 grams of fiber every day. A rule of thumb is one gets 2 grams of fiber per vegetable/fruit serving, so 5 servings of vegetables equals 10 gm of fiber.
  • Whole grains are a good source of fiber. One slice of whole grain bread is equal to a serving. A cup of cooked oatmeal is considered a serving. A thought for increasing fiber content is to use wheat berries, which cook like brown rice. Adding sunflowers to them can make a nutritious bundle.
    Wheat berries cook like brown rice and taste great when mixed with sunflower seeds!
    Wheat berries cook like brown rice and taste great when mixed with sunflower seeds!

    Cooked beans, peas , and lentils have 6 gm of fiber per half-cup of cooked item. They are excellent sources of fiber.

    Consider adding mung beans, which are bean sprouts that cook like lentils, in a dish with some olive oil, salt, and pepper and placing it over pasta.
    Consider adding mung beans, which are bean sprouts that cook like lentils, in a dish with some olive oil, salt, and pepper and placing it over pasta.

     

  • Always be certain that you check to see if a bread item is whole grain. Check the ingredient list. You want whole, sprouted, or malted wheat or whole grain on the label. Beware if it says wheat flour, for that is the same as white flour.
  • Put as many vegetables on your salad as possible. Lettuce has very little fiber.
  • Be certain to take in 5-10 grams a day of soluble fiber out of the 25-35 grams of fiber that is needed. Soluble fiber lowers cholesterol levels and feeds the healthy gut bacteria to support our immune system. An orange (medium) has 3-5 grams of soluble fiber, while a half cup of beans has 3-5 grams. Two tablespoons of ground flaxseed has 1.5 grams of soluble fiber. Flaxseed can be ground into flaxmeal.
  • Of note, a high fiber diet provides a low glycemic load, which is great for diabetics, but particle size of the fiber source is important. For example, old fashioned or scottish oats are best for fiber sources, whereas smaller particle sized grain products lose the fiber benefits. It turns out the glycemic index is higher in small-particles of grains (they get absorbed easier).
  • Higher glycemic-load foods are associated with chronic diseases. As people absorb more carbohydrates and gain weight, their insulin level increases in response, which promotes increased fat storage, thereby leading to the need for more insulin to control blood  sugar. This results in diabetes over time. Also cancer is more common in obese individuals as insulin-like growth factor (IL-GF) drives cancer growth. IL-GF is involved in glucose metabolism. A diet with a low glycemic load would include non-starchy vegetables except potatoes. Whole grains are high in glycemic load and make diabetes more difficult to contol. Pasta, rice, potato, and virus have high glycemic loads and are not as healthy. Fruit has high fiber content and a LOW glycemic index. High fat foods also have lower glycemic load. So aim for foods with lower glycemic indices as they allow for better body sugar control.
  • Fats affect inflammation in the body. High body fat content, especially abdominal fat,  is linked to cancer risk, diabetes, arthritis, Alzheimer’s disease, and autoimmune disorders. In an anti-inflammatory diet, one wants to avoid excess fat.  Decrease your fatty food intake, especially fried foods and fast foods. Decrease your dressings and mayonnaise on your foods. Decrease the amount of sweets in your diet, especially cookies and cake. Eat more fish and seafood (not fried) at least 2-3 times a week, except for farmed salmon, which should be eaten only once a month. Avoid sweetened beverages and limit foods with sweeteners. Eat more vegetables, fruits, whole grains, and beans.
    Beans are good!
    Beans are good!

    524-1147141

    Use extra virgin olive oil to toss in your vegetable or salad to allow easier coating of the leaves with your favorite dressing. By doing that, you will use less dressing and spread it out evenly!
    Use extra virgin olive oil to toss in your vegetable or salad to allow easier coating of the leaves with your favorite dressing. By doing that, you will use less dressing and spread it out evenly! Less dressing=Less fat!

     

  • Fat balance is important in your diet. Avoid the pro inflammatory fats, such as omega-6 polyunsaturated fats (PUFA) such as corn, cottonseed, soy, safflower, and sunflower oils, which are high in omega-6 oils. decrease your meat intake and decrease fish intake that are fed these products such as farm-grown salmon! Omega-3 PUFA are anti-inflammatory. and are present in flaxseed oil. Also, pasture-fed livestock (‘grass-fed’) have less omega-6 fatty acid in them. Avoid livestock that are fed grain or corn at any time, since that increases the amount of proinflammatoy PUFA in them. ‘Grass finished’ livestock means that the livestock ate grass until they are butchered. Choose grass-fed products only!
  • Some fat-health guidelines include avoiding fat soluble contaminants by eating food items lower on the food chain, such as smaller animals (fish) and avoiding farmed salmon. Eat only organic products. Avoid saturated fats, present in processed foods and dairy products or red meat. Avoid rancid fats by limiting aged cheese and meat (deli meat) in your diet. Chose healthy fats, which increase satiety and help absorb fat soluble vitamins. Healthy fats include avocados, olive oil, sardines, nuts, seeds, and olives.  Larger animals have more time to get contaminants in them. Chicken and sardines, which are lower on the food chain, live short lives. low in the food chain, and accumulate less toxins. Don’t eat fats that are solid at room temperature,. Avoid processed foods and meats (deli meats)
  • Rancid fats add oxidative stress to your body.Increase your monounsaturated fat intake such as avocado and olive oil, which are heart-healthy.  It was found that people who eat less saturated fat and more monounsaturated fats in their diet have better cognitive performance and verbal memory over time!
  • Osteoporosis prevention: Increase the following: exercise, calcium intake, vitamin D, protein and potassium . They all help build healthy bones! Protein is needed to build the bony matrix. Avoid caffeine (>300 mg a day) and avoid smoking and excessive sodium intake. Avoid being too thin. These factors all impact bone health in negative ways. Excessive sodium in the diet causes the kidneys to waste calcium in the urine. Be certain to get 1200 mg of calcium a day in the diet. For example, 1 or 2% no-fat milk has 300 mg of calcium per cup, while yogurt has 250 mg in 6 ounces. Please note that not all tofu has enough calcium in it, so check the labels. Also, corn tortillas (traditional mad with lime) has calcium in it ( fiver per day provides a lot of calcium)
  • Calcium bioavailability in the diet depends on the source of the calcium. There is calcium carbonate, calcium citrate, calcium malate, calcium phosphate, calcium gluconate, and calcium lactate. Tums has calcium carbonate in it and excessive use can decrease digestive enzymes and increase bloating gas production as a result, so avoid excessive tums. Avoid calcium from dolomite, bonemeal, and oyster shells (they have lead contaminants in them). Calcium mixed with Vitamin D and magnesium is an excellent supplement for bone health, especially as a 2:1 ratio (calcium 500mg/magnesium 250 mg). People absorb calcium better in small quantities through the day rather than a single large bolus. Be aware that calcium interacts with many medications and interferes with absorption of some medications, such as tetracyclines, biphosphonates, aspirin, and others. Some medications deplete calcium, such as aluminum antacids, steroids, anticonvulsannts, which deplete calcium supplies in the body. Calcium mixed with thiazide diuretics can lead to high, toxic blood levels of calcium in some people. Of note, a study recently suggested that calcium supplements may increase the risk of heart disease in some people by depositing in the coronary vessels. This appears to be not true.
  • Vitamin D is also an important component to bone health and body health. Deficiency in this vitamin has been associated with Alzheimer’s disease, autoimmune disorders, stroke, and musculoskeletal decline, among other things. Optimally, blood levels should be 30-80 ng/ml. The RDA for vitamin D in people aged 50-71 is 400 IU/day and for those over 70, the RDA is 600 IU/day. You can take up to 4000 IU/day safely per some sources. Vitamin D3 is the most active form of Vitamin D. Vitamin D is neccessary for optimal calcium and magnesium absorption in the gut. Our western style diet results in a high acid intake that leaches our bones. Chronic low grade acidosis in the body with our acidic diet, leads to bone derangement, especially in people with poor kidney function.
  • The shift to eating a better acid-base balanced diet can be made by including more plat foods in your diet (they are rich in alkaline materials). Consider this to boost bone health.
  • The recommended intake of protein is .4-.6 gm of protein per pound of weight. The average protein intake should be 55-100 gm per day. Protein content is high in beans, peas, and lentils (7 gm in a half cup) and high in poultry, fich, and lean meat (7 gm in 10 oz meat). Consider eating nuts and seeds for protein supplementation ( 7 gm in  1/4 cup, especially pumpkin seeds, which have 18 gms!)

Insane Medicine – Obesity increases your risk of Alzheimer’s disease.

  • Obesity increases your risk of diabetes, hypertension, stroke, and cancer. It also increases your risk of cognitive decline. It has been shown, however, that weight loss can reverse some of the cognitive decline! This was shown in patients with gastric bypass who were found to have improvements in their executive functioning after surgery and weight loss. Executive functioning includes the processes of organizing, planning, an decision-making. Also improved is attention and memory.
  • Also linked to this cognitive decline in obese people is lack of physical activity, poor inflammatory-type diet, and depression.
  • Increased fat causes problems in executive functioning, decreased memory, and  decreased processing speeds, all of which worsen with age as well. The high content of simple sugars and saturated fat cause a disruption in the blood-brain barrier that allow inflammation to occur in the brain, especially from the passage of Interleukin-1, which is secreted by fat and passes through this disrupted brain barrier. The hippocampus is the target that is affected, thereby diminishing memory by disrupting the connections in the brain called synapses. In the lab, lowering the brain’s level of interleukin-1 results in improved cognitive performance.

What to do? Emphasis on healthy choices and then weight loss:

  • Exercise regularly
  • Decrease stress through relaxation, meditation, or other routes.
  • Get plenty of sleep
  • From Harvard's healthy eating plate - one-half the plate is for fruits and vegetables, one-fourth with whole grains, the rest is devoted to fish, beans, nuts, or chicken - all unprocessed.
    From Harvard’s healthy eating plate – one-half the plate is for fruits and vegetables, one-fourth with whole grains, the rest is devoted to fish, beans, nuts, or chicken – all unprocessed.

    healthy-eating-plate-web1000

  • Eat a proper diet, less processed food, for example, use whole wheat bread and avoid processed meats such as hot dogs or salami. Choose low fat dairy products. Avoid additives or flavorings.Chose healthy plant oils such as canola and olive oils. Eat smaller portions of food.
  • Caffeine intake can  be safe in adults up to 400 mg a day and can increase wakefulness, better recall of spatial information, improved attention, faster reaction time,  and decrease feelings of fatigue.  It may also enhance memory and cognition as well. One study linked drinking three to five cups of coffee a day with a 65 % decrease in dementia. Caffeine was noted to decrease the formation of tau protein in the hippocampus of rats. Tau protein deposition is a hallmark of Alzheimer’s disease.  Caffeine enhances the brains’s memory and allows the consolidation of information for the long term.

Insane Medicine – Resveratrol in wine has multiple benefits – drink in moderation only though!

Insane Medicine - Wine
Red wine can benefit the body and the brain when taken in moderation.
  • Resveratrol is an antioxidant that may benefit the brain as a neuroprotecting agent. It neutralizes the effects of cell-damaging free radicals caused by pollution, stress, metabolism, aging, and other sources.
  • Resveratrol may protect against cardiovascular diseases, diabetes, and neurodegeneration.  It alters inflammation by affecting a class of enzymes called sirtuins that play a role in the aging process.
  • Resveratrol helps eliminate cell-damaging free radicals and enhances the survival mechanisms of cells. It may have anti-cancer properties as well.
  • Women should consume one 4 oz glass of wine per day at most and men can consume up to two 4 oz glasses of wine. Resveratrol is absorbed best by sipping the wine, as it’s absorption is enhanced by contacting the mucus membranes of the mouth.
  • Resveratrol may reduce beta-amyloids in the brain, which are associated with Alzheimer’s disease. It also helps modulate cell communication in the brain as well, which is important for memory. Resveratrol may also protect against oxidative stress and damage from diabetes.

Insane Medicine – Protecting your brain – the blood brain barrier

  • The brain is protected by the blood-brain barrier (BBB) which is composed of densely packed cells in the blood vessels that prevent entry of most substances into the brain. It does allow oxygen and nutrients, along with hormones to enter from the blood supply, but it blocks most other agents and bacteria. The BBB also removes brain waste matter such as beta-amyloid proteins that cause Alzheimer’s disease.
  • Breakdown of the BBB can result in catastrophic brain injury or death. It has been found that a number of factors can increase such a failure of the BBB. The first is sleep deprivation. In such cases, the BBB is weakened,allowing passage of drugs and chemicals that generally cannot enter the brain and results in brain damage.
  • High blood pressure, traumatic brain injury, obesity, viral infections, and inflammation also weaken the BBB. Again, a failed BBB results in brain damage slowly over time, especially by the accumulation of beta- amyloid, which leads to Alzheimer’s disease.

Preventing BBB failure:

  • Eat a diet high in Thiamine (Vitamin B-1) : pork, whole grains, sunflower seeds, kale, beans, and peas have a lot of Vitamin B-1.
  • Exercise regularly
  • Prevent brain injury: wear a helmet
  • Reduce cholesterol levels. High levels disrupt the BBB.
  • Consume caffeinated drinks, which block disruptions in the BBB.
  • Get at least 6-8 hours of sleep.
  • Lose weight, avoid obesity.
  • Avoid chemicals – some of which are toxic, such as polychlorinated biphenyls and the drug ecstasy, all of which disrupt the BBB.

Insane Medicine – Low Vitamin D is linked to a greater increased risk of Dementia!

Vitamin D
Vitamin D and its effects in the body.
  • The nervous system does not function normally without Vitamin D. It is involved in the synthesis of neurotransmitters such as dopamine, serotonin, and acetylcholine. Vitamin D protects against inflammation in the brain, particularly in the hippocampus, which is important in memory.
  • Vitamin D injections lessen age-related inflammation and also improve age-related memory impairments. In particular, it augments the removal of beta-amyloid plaques found in Alzheimer’s disease.
  • There is a strong association between vitamin D level and the risk of Alzheimer’s disease. In particular, people deficient in Vitamin D (levels less than 20ng/ml) have a 53% increase risk of becoming demented, and a 69% increase risk of getting Alzheimer’s disease. In severe Vitamin D deficiency (levels less than 10 ng/ml), the chance of Alzheimer’s is 122%!
  • Recommended intake of Vitamin D per the Institute of Medicine is 600 IU/day of Vitamin D for age under 70, and 800 IU/day for age over 70.
  • There is evidence that you can safely take up to 4000 IU/day of Vitamin D.
Vitamin D sources and effects with depletion
Vitamin D sources and effects with depletion

Insane Medicine – Key factors to prevent cognitive decline and dementia.

Insane Medicine -Preserve your mind to prevent cognitive decline
Insane Medicine -Preserve your mind to prevent cognitive decline.
  • Alzheimer’s disease results from accumulation in the brain of aberrant proteins (amyloid-beta and tau). This results in faulty connections in the brain and brain cell death. With that, memory and skills are lost over time.
  • 30 million people are affected by Alzheimer’s disease in 2010. One-third of these cases are attributable to modifiable risk factors such that there is a chance to prevent cognitive decline in some people. (Lancet Neurology, 2014)

There are controllable risk factors: What are they?:

  1. A lack of exercise.
  2. Smoking
  3. Poor diet
  4. Low level of education
  5. Depression
  6. Poor lifestyle
  7. Obesity
  8. High Blood pressure
  9. Uncontrolled diabetes.
  • Keeping a healthy hear may prevent dementia, in that reduced blood flow to the heart due to no exercise or poor diet also impacts flow to the brain as well. The above factors overlap in that depressed people may smoke more and get less exercise. They gain weight and also eat poorly.
  • Per the JAMA (July 2014) there has been a 24 % drop in first time strokes and a 20% drop in death from strokes. This is due to better control of risk factors causing strokes such as treating elevated blood pressure, stopping smoking, and statin use to control cholesterol levels.
  • It is important to stimulate your brain with mental activities and mental challenges such as cross-word puzzles or card playing. This resulted in greater brain volumes, especially in the hippocampus and better memory and executive functioning.
  • Moderate exercise in the 50-65 year range decreases the risk of cognitive decline significantly. The same was true for even older individuals (70 and above). SO be certain to exercise 30 minutes a day at least 5 days a week!