Monthly Archives: July 2017

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Can a Spoonful of Ceylon Cinnamon Make the Parkinson’s Go Down?

Parkinson’s disease is a degenerative disorder of the central nervous system in which dopamine generating cells in the substantia nigra die.  This then affects the motor system with regards to movement related activities, such as, shaking, rigidity, difficulty in walking and slowness in walking.

Two proteins in the brain act to protect neurons in the substantia nigra from cell death.  The first is Protein deglycase DJ-1 (DJ-1) which protects neurons against oxidative stress and cell death   The second is Parkin which helps degrade one or more proteins toxic to dopaminergic neurons.  The loss of function of the Parkin protein leads to dopaminergic cell death, which then can lead to Parkinson’s disease. Parkin and DJ-1 are known to stimulate and support the survival of existing dopaminergic neurons. It has been identified that Parkin and Protein deglycase DJ-1 decrease in the brain of Parkinson’s patients.  1

An interesting article published in the Journal of Neuroimmune Pharmacology in September 2014 entitled Cinnamon Treatment Upregulates Neuroprotective Proteins Parkin and DJ-1 and Protects Dopaminergic Neurons in a Mouse Model of Parkinson’s Disease explored a novel use of cinnamon in upregulating Parkin and DJ-1 and protecting dopaminergic neurons in a MPTP mouse model of Parkinson’s.

The authors from Rush University Medical Center’s Department of Neurological Sciences, Kalipada Pahan and Saurabh Khasnavis found that after oral feeding, ground cinnamon (Ceylon cinnamon (Cinnamonum verum)) is metabolized into sodium benzoate, which then enters into the brain, which then:  2

  • Stops the loss of Parkin and Protein deglycase DJ-1
  • Protects neurons
  • Normalizes neurotransmitter levels
  • Improves motor functions in mice with Parkinson’s

The authors also found that the oral treatment of MPTP-intoxicated mice with cinnamon powder and sodium benzoate:  3

  • Reduces the nigral expression of iNOS
  • Blocks nigral loss of Parkin and DJ-1
  • Protects the nigrostriatal axis
  • Restores locomotor activities

They suggested that cinnamon may be used to protect dopaminergic neurons in the nigra of Parkinson’s patients.

The authors of the study used True Cinnamon or Ceylon cinnamon (Cinnamonum verum) rather than using Chinese cinnamon (Cinnamomum cassia).  They stated that “Although both types of cinnamon are metabolized into sodium benzoate, by mass spectrometric analysis, we have seen that Ceylon cinnamon is much more pure than Chinese cinnamon as the latter contains coumarin, a hepatotoxic molecule.”  4

The use of Ceylon cinnamon could potentially be one of the safest approaches to halt disease progression in Parkinson’s patients.”  5

Ceylon cinnamon contains a major compound named cinnamaldehyde, which is converted into cinnamic acid by oxidation. In the liver, this cinnamic acid is β-oxidized to benzoate that exists as sodium salt (NaB) or benzoyl-CoA.   6

The authors concluded their study by stating, “Now we need to translate this finding to the clinic and test ground cinnamon in patients with PD. If these results are replicated in PD patients, it would be a remarkable advance in the treatment of this devastating neurodegenerative disease.”  7


It is important to note that if one is to consume a teaspoon or less of Ceylon cinnamon or True cinnamon (Cinnamonum verum) daily, it should be consumed in liquid or in food, and never in its dry form directly in the mouth as this could cause choking

Also make sure that you consume Ceylon cinnamon or True cinnamon (Cinnamonum verum or Cinnamomum Zeylanicum) and not Chinese cinnamon (Cinnamomum cassia or Cinnamomum Aromaticum) or Indonesian cinammon (Cinnamomum Burmanni) or Saigon cinammon (Cinnamomum Loureiroi), as these three cassia cinnamons can be hepatotoxic (damaging to the liver) in large quantities and on a frequent basis.

A common method of consuming Ceylon cinnamon or True cinnamon (Cinnamonum verum or Cinnamomum Zeylanicum) is to mix it in a smoothie with vegetables/fruit and protein powder.


Resources:

Cinnamon Vogue – CEYLON CINNAMON POWDER USDA ORGANIC

Ceylon cinnamon or True cinnamon (Cinnamonum verum)

Syzygium cumini: A Tree from the Indian Subcontinent with Multiple Health Benefits

Syzygium cumini, also known as jambul, jambolan, jamblang, or jamun, is an evergreen tropical tree in the flowering plant family Myrtaceae.  Syzygium cumini is native to the Indian Subcontinent and adjoining regions of Southeast Asia. The species ranges across India, Bangladesh, Pakistan, Nepal, Sri Lanka, Malaysia, the Philippines, and Indonesia.  

Syzygium_cumini_Tree_3

Syzygium cumini Tree

The name of the fruit is sometimes mistranslated as blackberry, which is a different fruit in an unrelated family.  In southern Asia, the tree is venerated by Buddhists, and it is commonly planted near Hindu temples because it is considered sacred to Lord Krishna.

The compounds in the tree, including the leaves, fruit, seeds and bark, include:  1

  • Anthocyanins
  • Glucoside
  • Ellagic acid
  • Isoquercetin
  • Kaemferol
  • Myrecetin

The fruit contains:

  • Raffinose
  • Glucose
  • Fructose
  • Citric acid
  • Mallic acid
  • Gallic acid
  • Anthocyanins
  • Delphinidin-3-gentiobioside
  • Malvidin-3-laminaribioside
  • Petunidin-3-gentiobioside
  • Cyanidin diglycoside
  • Petunidin
  • Malvidin

The seeds of the fruit contain:

  • Jambosine
  • Glycoside jambolin

The plant has been considered an anti-diabetic medicinal remedy throughout the Indian and Asian populations.  During the last four decades, numerous folk medicinal reports on the anti-diabetic effects of this plant have been cited in the literature. 

The Table below lists the various folk medicine uses of Syzygium cumini:

Folk medicinal uses of S. cumini (L.) Skeels.
Ethnic group used and their origin Plant part used, mode of preparation, administration and ailments treated References
Local people in southern Brazil Either infusions or decoctions of leaves of jambolan in water at an average concentration of 2.5 g/L and drank it in place of water at a mean daily intake of about 1 liter are used in the treatment of diabetes. [74]
Lakher and Pawi in North east India Infusion of fruit or mixture of powdered bark and fruit is given orally to treat diabetes. [75]
  Juice obtained from the seeds is applied externally on sores and ulcers.  
  Powdered seeds are mixed with sugar are given orally 2–3 times daily in the treatment of dysentery.  
  The juice of leaves is given orally as antidote in opium poisoning and in centipede bite.  
  The juice of ripe fruits is stored for 3 days and then is given orally for gastric problems.  
  The juice obtained from the bark is given orally for the treatment of women with a history of repeated abortion.  
Local informants in Maharastra, India Fruit and stem bark are used in the treatment of diabetes, dysentery, increases appetite and to relieve from headache [76]
Nepalese, Lepchas and Bhutias in northeast India Decoction of stem bark is taken orally three times a day for 2–3 weeks to treat diabetes [77]
Native amerindians and Quilombolas in North eastern Brazil Leaves are used in the treatment of diabetes and renal problems. [78]
Kani tribals in Southern India Two teaspoon of juice extracted from the leaf is mixed with honey or cow’s milk and taken orally taken twice a day after food for 3 months to treat diabetes. Fresh fruits are also taken orally to get relief from stomachache and to treat diabetes. [79]
  Young leaf is ground into a paste with goat’s milk and taken orally to treat indigestion.  
Malayalis in South India Paste of seeds is prepared with the combination of leaves of Momordica charantia and flowers of Cassia auriculata and taken orally once a day for 3 months to treat diabetes. [80]
Traditional medical healers in Madagascar Seeds are taken orally for generations as the centerpiece of an effective therapy for counteracting the slow debilitating impacts of diabetes. [35]
Local population in Andhra Pradesh, India Shade dried seeds are made into powder and taken orally thrice a day in the treatment of diabetes. [81]
Siddis in Karnataka, India The juice obtained from the leaves is mixed with milk and taken orally early in the morning, to treat diabetes. [82]
  The juice obtained from the stem bark is mixed with butter milk and taken orally every day before going to bed to treat constipation. The same recipe, when taken early in the morning on an empty stomach, is claimed to stop blood discharge in the faeces.  
Rural population in Brazil Leaves of jambolan are taken orally in the treatment of diabetes. [64]
Traditional healers in Brazil


Tea prepared from the infusion or decoction of leaves is taken orally to treat diabetes.


[83]


Tribal people in Maharastra The tender leaves are taken orally to treat jaundice. It was claimed that the eyes, nails and urine turned yellow. The treatment was followed for 2–3 days by adults and children as well. [84]

(Source:  Asian Pac J Trop Biomed. 2012 Mar; 2(3): 240–246.  doi:  10.1016/S2221-1691(12)60050-1)

The fruits, seeds and stem bark of Syzygium cumini possess promising activity against diabetes mellitus which has been confirmed by several experimental and clinical studies and considered its primary health benefit.

There are additional important health benefits of Syzygium cumini that have been studied and published.  They are listed in the Table below:

Health Benefits of Syzygium cumini (Jamun)

SystemConditionBenefitReferences
Gastrointestinal
Gastroprotective
A dose which consisted of 20.0 g tannins/kg rat weight showed significantly lower stomach free radical concentrations. These findings suggest that tannins extracted from S. cumini have gastroprotective and anti-ulcerogenic effects.1
Immunity
Anti-Inflammatory
These observations established the anti-inflammatory effect of S. cuminii seed extract in exudative, proliferative and chronic stages of inflammation along with an anti-pyretic action. Antiinflammatory and related actions of Syzigium cumini seed extract 2
The study concluded that S. cumini exhibits inhibitory role on inflammatory response to histamine, 5-HT and PGE2.3
The present study demonstrated that S. cumini bark extract has a potent anti-inflammatory action against different phases of inflammation without any side effect on gastric mucosa.4
Anti-bacterial and Anti-fungal
The water and methanolic extracts of Syzygium jambolanum seeds were examined for antibacterial and antifungal activity in vitro using the disc diffusion method, minimum inhibitory concentration, minimum bactericidal concentration and minimum fungicidal concentration. 5
The leaf essential oils of Syzygium cumini and Syzygium travancoricum were tested for their antibacterial property. The activity of S. cumini essential oil was found to be good, while that of S. travancoricum was moderate.6
Radioprotective
The radioprotective activity of the hydroalcoholic extract of jamun seeds (SCE) was studied in mice exposed to different doses of gamma radiation. The mice were injected with 0, 5, 10, 20, 40, 60, 80, 100, 120, 140 or 160 mg/kg body weight of SCE, before exposure to 10 Gy of gamma radiation, to select the optimum dose of radiation protection.
The mice treated with 80 mg/kg body weight SCE intraperitoneally before exposure to 6, 7, 8, 9, 10 and 11 Gy of gamma radiation showed reduction in the symptoms of radiation sickness and mortality at all exposure doses and caused a significant increase in the animal survival when compared with the concurrent double distilled water (DDW) + irradiation group. The SCE treatment protected mice against the gastrointestinal as well as bone marrow deaths and the DRF was found to be 1.24.
7
Syzygium cumini Linn. and Eugenia cumini (SCE) provided protection against the radiation-induced bone marrow death in mice treated with 10-60 mg/kg b.wt. of SCE. However, the best protection was obtained for 30 mg/kg b.wt. SCE, where the number of, survivors after 30 days post-irradiation was highest (41.66%) when compared with the other doses of SCE.8
Metabolism
Antioxidant
These data showed that in addition to 5 anthocyanidins, jamun contains appreciable amounts of ellagic acid/ellagitannins, with high antioxidant and antiproliferative activities.9
The leaves, bark and fruits of Terminalia arjuna, Terminalia bellerica, Terminalia chebula and Terminalia muelleri, the leaves and fruits of Phyllanthus emblica, and the seeds of Syzygium cumini were found to have high total phenolic contents (72.0-167.2 mg/g) and high antioxidant activity (69.6-90.6%).10
From the results, using different free radical-scavenging systems, it can be said that the fruit skin of S. cumini have significant antioxidant activity. In each case, lower antioxidant values, in comparison to tea, might be due to drying condition; through which some of antioxidants are presumably degraded. The antioxidant property of the fruit skin may come in part from antioxidant vitamins, phenolics or tannins and/or anthocyanins. Consumption of S. cumini fruit may supply substantial antioxidants which may provide health promoting and disease preventing effects.11
The present study reveals the efficacy of Eugenia jambolana seed kernel in the amelioration of diabetes, which may be attributed to its hypoglycemic property along with its antioxidant potential. The antioxidant effect of Eugenia jambolana seed kernel was also compared with glibenclamide, a standard hypoglycemic drug.12
Diabetes/Blood glucose
The present study reveals the efficacy of Eugenia jambolana seed kernel in the amelioration of diabetes, which may be attributed to its hypoglycemic property along with its antioxidant potential. The antioxidant effect of Eugenia jambolana seed kernel was also compared with glibenclamide, a standard hypoglycemic drug.13
In view of the knowledge summarized here, a successful clinical study should use S. cumini seeds, seed kernels or fruit from India in fairly high doses. Reductions on blood sugar levels by about 30% seem reasonably to be expected. Adverse effects to be expected comprise gastrointestinal disturbances.14
Study shows that S. cumini seed extracts reduce tissue damage in diabetic rat brain.15
Treatment with 400 mg per day of aqueous extracts of Momordica charantia (MC) and Eugenia jambolana (EJ) for 15 days substantially prevented hyperglycemia and hyperinsulinemia induced by a diet high in fructose (63.52+/-2.9 and 66.46+/-2.2 vs. 75.46+/-2.4, respectively).16
The oral antihyperglycemic effect of the water and ethanolic extracts of the fruit-pulp of Eugenia jambolana (EJ) was investigated in alloxan-induced diabetic with fasting blood glucose between 120 and 250 mg/dl as well as severely diabetic rabbits (fasting blood glucose above 250 mg/dl). Water extract was found to be more effective than the ethanolic extract in reducing fasting blood glucose and improving blood glucose in glucose tolerance test.
After treatment of diabetic and severely diabetic rabbits daily once with 25mg/kg, body weight with F-III for 7 and 15 days, respectively, there was fall in fasting blood glucose (38% diabetic; 48% severely diabetic) and improvement in blood glucose during glucose tolerance test (48%) in diabetic rabbits.
17


Resources:

Deep Foods – Frozen Jamun Fruit

Jamun Powder (Syzygium cumini)

Vedic Juices Organic Jamun Indian BlackBerry Juice 1 Liter 12 Packs

Basic Ayurveda – Jamun Juice

 

Flip Your AMPK switch to the “ON” position

Introduction to AMPK

AMPK (adenosine monophosphate-activated protein kinase) is an enzyme contained in every cell of the human body that serves as the body’s master regulating switch.

When the AMPK master switch is turned “ON” (by activating AMPK), it inhibits multiple damaging factors of aging and enables cells to become revitalized.  Scientists have found that activated AMPK promotes longevity factors that have been shown to extend life span in numerous organisms.  1  2 

There are various studies that show an increase in AMPK supports:

  • Reduced fat storage 3 
  • New mitochondria production  4 
  • Promotion of healthy blood glucose and lipids already within normal range  5 

dmso-7-241Fig1

Roles of AMPK in the control of whole-body energy metabolism. Notes: Activation of AMPK (green lines) stimulates the energy-generating pathways in several tissues while inhibiting the energy-consuming pathways (red lines). In skeletal muscle and heart, activation of AMPK increases glucose uptake and fatty acid oxidation. In the liver, AMPK activity inhibits fatty acid and cholesterol synthesis. Lipolysis and lipogenesis in adipose tissue are also reduced by AMPK activation. Activation of AMPK in pancreatic β-cells is associated with decreased insulin secretion. In the hypothalamus, activation of AMPK increases food intake.  Source: AMPK activation: a therapeutic target for type 2 diabetes? Kimberly A Coughlan, Rudy J Valentine, Neil B Ruderman, and Asish K Saha, Diabetes Metab Syndr Obes. 2014; 7: 241–253. Published online 2014 Jun 24. doi: 10.2147/DMSO.S43731

Activating AMPK:  Turning the Switch “ON”

The two major methods of activating AMPK is through:

  • exercise and
  • calorie restriction

When you exercise, you use up more ATP which generates higher AMP levels, which then activates AMPK.  6

The other method of activating AMPK is through calorie restriction by at least 30%.  This means cutting daily calorie consumption by 30%.  By reducing calorie consumption, the lower levels of available energy leads to rising AMP levels, which then activates AMPK.  7

In addition to exercise and calorie restriction, there are many other ways to activate AMPK, particularly through certain foods, herbs and nutraceuticals.  The Table below lists the many researched methods of activating AMPK:

AMPK Activators

CategorySubstance/ActivityReferences
Physiological
Exercise1
Fasting and Intermittant Fasting2
Cold water exposure (raise AMPK in the hypothalamus)3
Calorie Restriction4
Foods
Extra Virgin Olive Oil 5
Royal Jelly (10-Hydroxy-2-decenoic acid (10H2DA)6
Dashi kombu (Laminaria japonica Areschon)7
Bitter Orange (Citrus aurantum Linn)8
Garlic and Olives (Oleanolic acid)9
Apple Cider Vinegar10
Rose Hips (Trans-Tiliroside)11
Mulberry leaves extracts12
Fish Oil – EPA , DHA 13 14
Anthocyanins 15
Bitter melon16
Fungi
Reishi17
Herbs and Spices
Cinnamon 18
Astragalus 19 20
Marijuana (Cannabinoids)21
Green Tea/EGCG22
Rooibos23
Danshen (Chinese Red Sage)24
Gynostemma pentaphyllum (Jiagulon)25
Baicalin26 27
Hormones
Adiponectin 28 29
Thyroid hormones, especiallly T3 30
Leptin31
Nitric Oxide32 33
Immune System
Interleukin-6 (IL-6)34
Nutraceuticals
Apigenin35
Berberine36
Butyrate (Calcium/Magnesium ) or Sodium Butyrate (Short Chain Fatty-Acid)37
Carnitine38
Co-enzyme Q1039
Creatine40
Curcumin41
Fucoidan42
Genistein43
Glucosamine44 45
Hydroxytyrosol46
Oxaloacetate47
Quercetin48 49
Red yeast rice50
Resveratrol51
R-Lipoic Acid52 53
Vitamin E - gamma tocotrienol54
Pharmaceuticals
Aspirin55
Metformin56


Informational References:

Life Extension – AMPK and Aging “A Technical Review”  (November 2015)

The Multiple Health Benefits of Citrus Bergamot

Citrus Bergamot

Citrus bergamia Risso, also known as the bergamot orange or Citrus bergamot, is a fragrant citrus fruit the size of an orange, with a green color similar to a lime.  The word bergamot is etymologically derived from the Italian word “bergamotto”.

Image result for citrus bergamot

Figure 1.  Citrus bergamot on the vine  (Source)

Citrus bergamot is a citrus plant that grows almost exclusively in the narrow coastal Calabria region in Southern Italy, due to sensitivity to the weather and soil conditions.   It is cultivated in Italy for the production of bergamot oil, a component of many brands of perfume and tea, especially Earl Grey tea. 

While bergamot is native to Italy, it is now widely distributed throughout the subtropical regions of China, including Guangdong, Guangxi, Fujian and Yunnan.

Image result for citrus bergamot

Figure 2.  Citrus Bergamot  (Source)

Genetic researchers have found that the bergamot orange is probably a hybrid of Citrus limetta and Citrus aurantium.

Citrus bergamia is sometimes confused with (but is not the same as):

  • Citrus medica (citron, the yellow fruit of which is also known as etrog)
  • Citrus limetta, the “sweet lemon” or “sweet lime”

Citrus Bergamot differs from C. Aurantium as Citrus Bergamot does not contain Synepherine, N-methyltyramine, and octopamine, which have been shown in research to constrict arteries, increase blood pressure, increase heart rate, cause heart-rhythm disorders, heart attack, and stroke.

Bio-Active Ingredients of Citrus Bergamot

The bio-active ingredients in citrus bergamot includes a unique profile of flavonoid and glycosides, such as:  1  2

  • brutieridin
  • melitidine
  • naringin
  • neodesmin
  • neoeriocitrin
  • neohesperidin
  • ponceritin
  • poncirin
  • rhoifolin
  • rutin

Health Attributes of Citrus Bergamot

A number of studies have shown the positive and powerful health attributes of citrus bergamot.  Among these attributes include:

  • anti-inflammatory  3
  • anti-hypertensive  4
  • hepatic protective effects  5
  • promotes digestion  6 

A clinical study found reduced total low-density lipoprotein, cholesterol, triglyceride and blood glucose levels in 237 patients who had taken oral BPF for 30 days.  7 

Moreover, the expression levels of two autophagy markers (LC3 II/I and Beclin-1) were increased while SQSTM1/p62 expression was reduced, indicating that BPF could stimulate autophagy.  8 

Naringin has been shown to be beneficial in animal models of atherosclerosis, while neoeriocitrin and rutin have been found to exhibit a strong capacity to prevent LDL from oxidation.

Brutieridine and melitidine has been shown to have the ability to inhibit HMG-CoA reductase.

Bergamonte®

Bergamonte® is an exclusive product produced by HP Ingredients which contains bioactive compounds of extract of the juice and albedo of citrus bergamia risso. 

HP Ingredients is a fasty growing innovative herbal and nutraceutical extract health company focused on bringing effective remedies from Asia, Italy, and Chile to the North American Market. HP Ingredients is dedicated to innovating new products and providing accurate and timely information on benefits of these well-researched extracts. We work closely with several teams of scientists from University of Malaysia and Forest Research Institute of Malaysia, the Universidad Austral de Chile, and the University Magna Graecia.

Bergamonte®, an extract of the bergamot orange, was shown in a double-blind, placebo-controlled study to:

  • Support the healthy balance of HDL to LDL cholesterol
  • Support healthy triglycerides and total cholesterol levels
  • Promote healthy blood sugar levels already in the normal range

Melitidine and Brutieridine

A published research article in the Journal of Natural Products 2009 showed that bergamot juice contained novel compounds with statin like principles, having the 3-hydroxy3-methylglutaric acid (HMG) found to the naringin (melitidine) and neohesperidin (brutieridine).

These novel compounds interfere with the natural synthesis of the cholesterol pathway in the human body: The HMG-CoA substrate interferes with the synthesis of the mevalonate acid, blocking the cholesterol production.

Superior Full-Spectrum Antioxidant ORAC Potency

Mode of Action

  • Inhibiting HMG-CoA Reductase
  • Inhibiting Phosphodiesterases PDEs
  • ‘Activating’ AMPK

Efficacy Findings from Clinical Trials

In an unpublished human clinical trial involving 192 patients, the following are the result after patients consumed 100ml of Citrus Bergamot juice for 30 days.

Hypolipemic and Hypoglycemic Activity of Bergamot Polyphenolic Fraction

Fitoterapia 82 (Nov 2011) 309–316
237 patients with hyperlipemia, hypercholesterolemic (HC, cLDL, low cHDL), mixed dyslipidemic (HC and TG), or metabolic syndrome (HC, HT, and HG) were taking either placebo, 500mg, 1000mg.

The effect of Bergamot Polyphenolic Fraction (500 and 1000 mg/daily) on reactive vasodilatation in patients suffering from isolated (HC) or mixed hyperlipidemia (HC/HT) and associated hyperglycemia (HC/HT /HG).

Bergamot Polyphenolic Fraction reduces total and LDL cholesterol levels (an effect accompanied by elevation of cHDL), triglyceride levels and by a significant decrease in blood glucose. Moreover, it  inhibited HMG-CoA reductase activity and enhances reactive vasodilation.

Supports healthy cholesterol level, increase LOX-1 expression and Protein Kinase B phosphorylation

International Journal of Cardiology, 2013
In this open-label, parallel group, placebo-controlled study, 77 patients were randomly assigned either placebo, Rosuvastatin, Bergamot Polyphenolic Fraction or combination of Bergamot Polyphenolic Fraction with Rosuvastatin for 30 days.

Both doses of rosuvastatin and Bergamot Polyphenolic Fraction help support healthy cholesterol level and reduce urinary mevalonate compared to control group. The benefits are associated with significant reductions of biomarkers used for detecting oxidative vascular damage, including malondialdehyde, oxyLDL receptor LOX-1 and phosphoPKB.

Effects on LDL Small Dense Particles, Metabolic Biomarkers, and Liver Function

Advances in Biological Chemistry, 2014, 4, 129-137
107 patients with metabolic syndrome and non fatty liver disease were given either placebo or 650 mg of Bergamot Polyphenolic Fraction twice a day for 120 days. Bergamot Polyphenolic Fraction group showed significant reduction in fasting plasma glucose, rotal cholesterol, LDL cholesterol, triglycerides, and increase of HDL cholesterol. Bergamot Polyphenolic Fraction decrease IDL particles by 51%, increase large LDL by 38%, decrease small LDL by 35%, and 20% increase of total HDL particles. Hepatorenal index was significantly reduced by 46%, accompanied by reduction of hepatic ultrosonographic pattern of steatosis by 99%. This suggests Bergamot Polyphenolic Fraction improves both liver function and inflammation as confirmed by reduction of TNF-α and CRP.

Product Comparison

Already within the normal range  

References
References
  1. Ross Walker, Elzbieta Janda and Vincenzo Mollace. The Use of Bergamot-derived Polyphenol Fraction in Cardiometabolic Risk Prevention and its Possible Mechanisms of Action. Cardiac Health and Polyphenols. Chp 84, Pg 1085-1103, 2014
  2. Micaela Gliozzi, Ross Walker, Elzbjeta Janda, Vincenzo Mollace. Bergamot polyphenolic fraction enhances rosuvastatin-induced effect on LDLcholesterol, LOX-1 expression and Protein Kinase B phosphorylation in patients with hyperlipidemia. International Journal of Cardiology Dec 2013, 170(2):140-5
  3. Vincenzo Mollace, Iolanda Sacco, Elzbieta Janda, Claudio Malara, Domenica Ventrice, Carmen Colica, Valeria Visalli, Saverio Muscoli. Hypolipemic and hypoglycaemic activity of bergamot polyphenols: From animal models to human studies. Fitoterapia 82 (2011) 309–316
  4. Celia C, Trapasso E, Locatelli M, Navarra M, Ventura CA, Wolfram J, Carafa M, Morittu VM, Britti D, Di Marzio L.. Anticancer activity of liposomal bergamot essential oil (BEO) on human neuroblastoma cells. Colloids Surf B Biointerfaces. 2013 Dec 1;112:548-53
  5. Delle Monache S, Sanità P, Trapasso E, Ursino MR, Dugo P, Russo M, Ferlazzo N, Calapai G, Angelucci A, Navarra M. Mechanisms underlying the anti-tumoral effects of Citrus Bergamia juice. PLoS One. 2013 Apr 16;8(4)
  6. Kang P, Suh SH, Min SS, Seol GH. The essential oil of Citrus bergamia Risso induces vasorelaxation of the mouse aorta by activating K(+) channels and inhibiting Ca(2+) influx. J Pharm Pharmacol. 2013 May;65(5):745-9
  7. Leopoldini M, Malaj N, Toscano M, Sindona G, Russo N. On the inhibitor effects of bergamot juice flavonoids binding to the 3-hydroxy-3-methylglutaryl-CoA reductase (HMGR) enzyme. J Agric Food Chem. 2010 Oct 13;58(19):10768-73
  8. Di Donna L, De Luca G, Mazzotti F, Napoli A, Salerno R, Taverna D, Sindona G. Statin-like principles of bergamot fruit (Citrus bergamia): isolation of 3-hydroxymethylglutaryl flavonoid glycosides. J Nat Prod. 2009 Jul;72(7):1352-4
  9. Mollace V, Ragusa S, Sacco I, Muscoli C, Sculco F, Visalli V, Palma E. The protective effect of bergamot oil extract on lecitine-like oxyLDL receptor-1 expression in balloon injury-related neointima formation. J Cardiovasc Pharmacol Ther. 2008 Jun;13(2):120-9
  10. Natalizia Miceli, Maria Mondello, Maria Mondorte, Vasileios Sdrafkakis, Paola Dugo, Maria Crupi. Hypolipidemic effects of bergamot juice in rats Fed a Hypercholesterolemic Diet. J. Agric. Food Chem., Vol. 55, No. 26, 2007

Chinese Herbal Decoction Ge-Gen-Qin-Lian: An Effective Treatment for Type 2 Diabetes

A Traditional Chinese Medicine (TCM) herbal formula that has been used for the treatment of type-2 diabetes, and which has been documented based on clinical trials, is the Ge-Gen-Qin-Lian decoction (GGQLD).

A number of recent studies from 2011 and 2015 have showed that GGQLD had good clinical effects on type-2 diabetes and the anti-diabetic activities of GGQLD in vivo and in vitro were investigated.  1  2 

GGQLD consists of four herbs:

  • Puerariae Lobatae radix (Ge-Gen) as the principle herb
  • Scutellariae radix (Huang-Qin)
  • Coptidis rhizoma (Huang-Lian)
  • Glycyrrhizae Radix et Rhizoma Praeparata cum Melle (Gan-Cao)

Each of these 4 herbs have primary bioactive compounds that are effective in treating and reducing blood glucose level.  The primary bioactive compounds from these 4 herbs and their effect include:

Ge-Gen

Puerarin from Ge-Gen reduced blood sugar in diabetic mice, and improved insulin resistance and hyperlipidemia in rats  3 

Huang-Qin

Baicalin from Huang-Qin had antihyperglycemic effects on diabetic rats  4 

Huang-Lian

Berberine from Huang-Lian lowered blood glucose significantly by increasing insulin receptor expression  5

Gan-Cao

Amorfrutins from Gan-Cao have potent antidiabetic activity  6 

Another key component of GGQLD that has been identified called 4-Hydroxymephenytoin is involved in the antidiabetic ingredients of GGQLD stimulating endogenous insulin secretion and ameliorating insulin resistance in 3T3-L1-based insulin resistance models.  7

The Table below lists the antidibetic ingredients in Ge-Gen-Qin-Lian:  (Source) 

Potential antidiabetic ingredients in Ge-Gen-Qin-Lian formula by network target analysis.
Ingredients Herbs CID Literature evidence
4-Hydroxymephenytoin Ge-Gen 119507 /
1-OCTEN-3-OL Ge-Gen 18827 [50]
Berbericinine Huang-Lian 19009 /
Berberine bisulfate Huang-Lian 12457 [51]
Columbamine Huang-Lian 72310 [52]
Coptisine Huang-Lian 72322 [53]
Epiberberine Huang-Lian 160876 [54, 55]
Jatrorrhizine Huang-Lian 72323 [55, 56]
Oxyberberine Huang-Lian 11066 [57]
Dehydrocheilanthifoline Huang-Lian 3084708 [58]
Berberine Huang-Lian 2353 [59]
Indole Huang-Qin 798 [60]
1,3-Diphenylbenzene Huang-Qin 7076 /
2-Formylpyrrole Huang-Qin 13854 /
Guaifenesin Huang-Qin 3516 [61]
1-(1H-Pyrrol-2-yl)ethanone Gan-Cao 14079 [62]
2-Acetyl-1-methylpyrrole Gan-Cao 61240 [63]
m-Ethylphenyl acetate Gan-Cao 76462 /
5,6,7,8-Tetrahydro-4-methylquinoline Gan-Cao 185667 /
/: no evidence.

Modulating the Genetic Factors (ApoE) of Alzheimer’s Disease With Positive Behaviors and Natural Substances

Causitive Factors of Dementia and Alzheimer’s Disease

It is generally believed that the onset of dementia and Alzheimer’s disease is the consequences of complex interactions among:  1

  • genetic factors
  • environmental factors
  • lifestyle factors

The main features of dementia and Alzheimer’s disease are the presence of:

  • extracellular amyloid beta protein plaques
  • intracellular neurofibrillary tangles of tau proteins (NFTs)
  • loss of neurons and synapses in the cerebral cortex and certain subcortical regions in the brain

Image result for amyloid beta plaques

Figure 1.  Amyloid beta protein plaques and intracellular neurofibrillary tangles of tau proteins  (Source)

Image result for loss of neurons and synapses in the cerebral cortex

Figure 2.  Loss of neurons and synapses in the cerebral cortex  (Source)

This article focuses on the genetic factors as a potential cause for the late-onset of Alzheimer’s disease and what actions can be taken to modulate these genetic factors as it related to the most important genetic factor known as apolipoprotein E (ApoE).

Genetic Factors

Studies have demonstrated that Alzheimer’s disease is related to polymorphisms of at least four (4) genes:

  • amyloid precursor protein (APP)
  • presenilin (PS-1)
  • presenilin (PS-2)
  • apolipoprotein E (ApoE)

Polymorphisms in the three genes, amyloid protein precursor (APP), presenilin (PS)-1 and PS-2, is estimated to be the cause of early-onset (which is less than 60 years of age) autosomal dominant Alzheimer’s disease, which accounts for less than 1% of Alzheimer’s disease cases.  2

There are multiple genetic, environmental and lifestyle factors involved in late-onset Alzheimer’s disease, yet impairment in amyloid-beta clearance by ApoE is a major contributor to development of the disease.

Apolipoprotein E (ApoE)

Apolipoprotein E (ApoE) is a class of apolipoprotein found in the chylomicron and Intermediate-density lipoprotein (IDLs) that is essential for the normal catabolism of triglyceride-rich lipoprotein constituents. 

ApoE is mainly produced by astrocytes, and transports cholesterol to neurons via ApoE receptors, which are members of the low density lipoprotein receptor gene family.  ApoE is the principal cholesterol carrier in the brain and encodes for a protein that transports cholesterol, fats and fat-soluble vitamins through the blood.  

ApoE also contributes to the maintenance and repair of nerve cells.

PBB Protein APOE.jpg

Figure 3.  Apolipoprotein E (ApoE)  (Source)

There are three (3) major polymorphisms or alleles in the ApoE gene:

  • ApoE-ε2  (good one)
  • ApoE-ε3  (neutral)
  • ApoE-ε4  (problematic)

Since we carry two copies of the APOE gene, one from our mother and one from our father, the combination of alleles determines our ApoE3 genotype, for which there are six possible genotypes:

  • E2/E2
  • E3/E3
  • E4/E4
  • E2/E3
  • E2/E4
  • E3/E4

The ApoE-ε2 polymorphism, the most desirable to have, is associated with lower cholesterol levels and it actually may protect against Alzheimer’s disease in some populations and may decrease the risk.  3  

The ApoE-ε3 allele has a frequency of approximately 79 percent and is considered the “neutral” Apo E genotype. This means that for 79% of the population, a genetic polymorphism of this gene does not cause dementia or heart disease.  

The E2 allele is the one that is the most efficient in clearing and removing the amyloid-beta plaques from the brain.  The second most efficient allele is the E3 version, which does an average job of removing amyloid-beta plaques.

The E4 allele is the least efficient version in removing and clearing amyloid-beta plaques from the brain.  This results in more plaques building up and creating a much greater risk of developing Alzheimer’s disease.

The best genotype to have is E2/E2.

The worst genotype to have is E4/E4.

There are certain percentages of the population that carry certain genotypes:

  • Around 55% of the population have the E3/E3 genotype, which is the most common, equating to average risk  
  • Around 25% of the population have the E3/E4 genotype
  • Around 15% of the population have the E2/E3 genotype

ApoE-ε4 Allele

ApoE-ε4 is a major genetic risk factor for late-onset Alzheimer’s disease.  

Individuals carrying the E4 allele are at an increased risk of Alzheimer’s disease.  Having one allele of ApoE4 increases the risk of Alzheimer’s disease, and if two ApoE4 alleles are present, the risk is even higher.  15

However, many individuals with the ApoE-ε4 allele never develop the disease and many patients with Alzheimer’s disease do not have the ApoE-ε4 allele.  

With an allele frequency of approximately 14%, the ApoE-ε4 polymorphism has been implicated in the following diseases:

  • atherosclerosis  4
  • Alzheimer’s disease  5
  • impaired cognitive function  6
  • reduced hippocampal volume  7 
  • HIV  8 
  • faster disease progression in multiple sclerosis  9
  • unfavorable outcome after traumatic brain injury  10 
  • ischemic cerebrovascular disease  11 
  • sleep apnea  12
  • accelerated telomere shortening  13
  • reduced neurite outgrowth  14  

Image result for Apolipoprotein E

Figure 4.  Apolipoprotein E and Alzheimer disease  (Source)

Those patients with two ε4 alleles of the APOE gene have up to 20 times the risk of developing Alzheimer’s disease.  16  The lifetime risk estimate of developing Alzheimer’s disease for individuals with one copy of the apoE4 allele (approximately 25% of the population) is approximately 30%. 17

According to the National Institute of Health, inheriting a single copy of ApoE4 from a parent increases the risk of Alzheimer’s disease by about three-fold. Inheriting two copies, one from each parent, increases the risk by about 12-fold.

ApoE generally is an anti-inflammatory and is able to break down the amyloid beta proteins that are a cause of Alzheimer’s disease.  The ApoE-ε4 allele is limited in its ability to function as an anti-inflammatory and to break down amyloid beta proteins. 18

Increasing the Production and Function of ApoE-ε4

If a person has one E4 allele or two E4 alleles (E4/E4, which is the worst and carries the highest risk for Alzheimer’s disease), then they can and should take proactive and aggressive preventive action to increase the production and function of the ApoE-ε4 allele.

You ultimately want your ApoE working effeciently to help control and remove the harmful buildup of amyloid-beta plaques.

Since the ApoE-ε4 allele does not function as efficiently as the ApoE-ε2, there are certain behaviors that can be done and substances that can be taken to increase its production and function. 

Behavioral Actions

There are certain behavioral actions that can be taken to increase to production and function of the ApoE, such as:

  • Eat a Ketogenic diet  19
  • APOE Stabilization by Exercise  20
  • Reduce elevated total cholesterol level and blood pressure 21
  • Learning and education (allowing the brain to constantly learn new and interesting in-depth subjects)  
  • 22

Natural Substances that Increase the Production and Function of ApoE-ε4

There are also natural substances that be consumed that have shown to increase the production and function of ApoE, especially in the case of a low functioning E4 single of double allele.  

These substances are listed in the Table below:

Increasing the Production and Function of ApoE-ε4

CategorySubstanceReference
Fatty Acids
DHA Ref.
Butyrate Ref.
Polyphenols
Curcumin Ref.   Ref.
Vitamins
Vitamin A (Retinol)   Ref.
Citicoline (cytidine diphosphate-choline (CDP-Choline) Ref.

Resources:

In order to see what your genotype in the ApoE gene, especially if your have the ApoE-ε4 polymorphism, you need to order a DNA and Genetic Test.  There are a number of testing companies.  The most popular are:

23andMe

Ancestry

Genos

Once you have ordered and received your DNA and Genetic Test from the testing company, you can then download your data to one of a number of websites that will analyze your genetic data and provide information on the polymorphisms of the ApoE gene and your specific genotype. 

A number of companies will analyze your genetic data and include:

SelfDecode

Livewello

Infinome

Promethease

Codegen.eu

All of the 5 companies above will receive the 23andMe genetic data.

Another way to test for your genotype and the ApoE-ε4 polymorphism can be done by ordering the following test from Life Extension:

Life Extension – ApoE Genetic Test for Alzheimer’s and Cardiac Risk

Sample Report (PDF)

Videos:

Dr. Ben Lynch – Alzheimer’s Dirty Gene APOE4

AHS16 – Steven Gundry – Dietary Management of the Apo E 4

NutritionFacts.org – The Alzheimer’s Gene: Controlling ApoE

Apo E Gene’s connection with Alzheimer’s Disease, Heart Disease and more

Do you have Apo E 4 Dementia risk, Heart Attack diet risk; Apo(e) 4 and alcohol