Category Archives: Inflammation

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The Multiple Health Benefits of Tributyrin, a Triglyceride Form of Butyrate

Short-Chain Fatty Acids

A considerable amount of scientific interest has been focused on short chain fatty acids (SCFAs) for improving colonic and systemic health, and specifically reducing the risk of inflammatory diseases, diabetes, and cardiovascular disease.

Researchers have shown that SCFAs have distinct physiological effects:  1

  • they contribute to shaping the gut environment
  • they influence the physiology of the colon
  • they can be used as energy sources by host cells and the intestinal microbiota 
  • they also participate in different host-signaling mechanisms

Prebiotics, which consist of primarily dietary carbohydrates such as resistant starch and dietary fibers, are the substrates in the large intestine for fermentation that produce SCFAs.  The other source of SCFA, although in smaller amounts than dietary carbohydrates, are amino acids.  Three amino acids:

  • valine
  • leucine
  • isoleucine

obtained from protein breakdown can be converted into isobutyrate, isovalerate, and 2-methyl butyrate, known as branched-chain SCFAs (BSCFAs), which contribute very little (5%) to total SCFA production.  2

There are seven short-chain fatty acids that are produced by the large intestine through the fermentation of dietary fiber and resistant starch.  Of these seven short-chain fatty acids, three of them are the most important and common:

  • acetate
  • propionate
  • butyrate

These three represent about 90–95% of the SCFA present in the colon.  The rate and amount of SCFA production depends on the species and amounts of microflora present in the colon, the substrate source and gut transit time.

Butyrate is the major energy source for colonocytes. Propionate is largely taken up by the liver. Acetate enters the peripheral circulation to be metabolized by peripheral tissues and is the principal SCFA in the colon, and after absorption it has been shown to increase cholesterol synthesis.

Image result for Short-Chain Fatty Acids

Figure 1.  Fibers, specific oligosaccharides and resistant starch reach the colon intact, where they induce shifts in the composition and function of intestinal bacteria (shifts indicated by different colors). Intestinal bacteria use these compounds as substrates for the production of the short-chain fatty acids acetate, propionate and butyrate. These microbial metabolites are taken up by intestinal epithelial cells called enterocytes. Butyrate mainly feeds the enterocytes, whereas acetate and propionate reach the liver by the portal vein.  (Source:  You are what you eat,  Nature Biotechnology  32, 243–245 (2014) doi:10.1038/nbt.2845)

Butyrate (Butyric Acid)

The most important short-chain fatty acid is butyrate.

Butyrate is a primary energy source for colonic cells.  3 4   Butyrate also has demonstrated anti-inflammatory properties.  5  Butyrate may also have a role in preventing certain types of colitis. A diet low in resistant starch and fiber, which will result in a low production of SCFAs in the colon, may explain the high occurrence of colonic disorders seen in the Western civilization.  6

Studies have demonstrated that butyrate has anti-carcinogenic properties:

  • It inhibits the growth and proliferation of tumor cell lines in vitro.  7
  • It induces differentiation of tumor cells, producing a phenotype similar to that of the normal mature cell.  8
  • It induces apoptosis or programmed cell death of human colorectal cancer cells.  9 10
  • It inhibits angiogenesis by inactivating Sp1 transcription factor activity and down regulating VEGF gene expression. 11

Butyrate has been studied for its role in nourishing the colonic mucosa and in the prevention of cancer of the colon, by promoting cell differentiation, cell-cycle arrest and apoptosis of transformed colonocytes; inhibiting the enzyme histone deacetylase and decreasing the transformation of primary to secondary bile acids as a result of colonic acidification.

Therefore, a greater increase in SCFA production and potentially a greater delivery of SCFA, specifically butyrate, to the distal colon may result in a protective effect.   12

Butyrate is mainly taken up by the colon epithelial cells, only small amounts reach the portal vein and the systemic circulation.  The primary beneficial effects of butyrate occurs at the intestinal level, yet there are additional benefits at the extra intestinal level:

Intestinal effects

  • Is the preferred energy source for the colon epithelial cells
  • Decreases the pH of the colon (which decreases bile salt solubility, increases mineral absorption, decreases ammonia absorption, and inhibits growth of pathogens)
  • Stimulates proliferation of normal colon epithelial cells
  • Prevents proliferation and induces apoptosis of colorectal cancer cells
  • Affects gene expression of colon epithelial cells
  • Plays a protective role against colon cancer and colitis
  • Improves the gut barrier function by stimulation of the formation of mucin, antimicrobial peptides, and tight-junction proteins
  • Interacts with the immune system and regulates immune function
  • Has anti-inflammatory effects
  • Stimulates the absorption of water and sodium
  • Reduces oxidative stress in the colon
  • Assists in ion absorption
  • Assists in proper intestinal motility
  • Induces cell cycle arrest, differentiation, and apoptosis in colon cancer cells

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Figure 2.  The multiple effects of butyrate at the intestinal level.  (Source:  Potential beneficial effects of butyrate in intestinal and extra intestinal diseases)

Extra intestinal effects  13

  • Insulin sensitivity
  • Cholesterol synthesis
  • Energy expenditure
  • Ammonia scavenger
  • Stimulation of β-oxidation of very long chain fatty acids and peroxisome proliferation
  • CFTR function
  • Neurogenesis
  • HbF production

Tributyrin

The major problem with butyrate is achieving high concentrations in the blood. Butyrate is metabolized rapidly as soon as it enters the enteroocytes via its active transport system, and its plasma concentrations are far below those required to exert its antiproliferative/differentiating actions.  14 

An alternative and more advantageous form of butyric acid is the triglycerine form called Tributyrin, also known as glyceryl tributyrate. Tributyrin is a triglyceride containing 3 molecules of butyric acid which are bound by a glycerol molecule. 

Tributyrin is naturally present in butter in trace amounts.  However, it is not recommended to consume butter as a means to obtain therapeutic amounts of tributyrin.  There is no point to recommend consuming butter to someone if the intention is to increase butyric acid consumption.

As an alternative to consuming butter, tributyrin can now be consumed in the form of a supplement or a food additive and can provide considerable amounts of butyrate to the intestine in addition to the endogenous production of SCFAs (butyrate) from the fermentation of dietary fibers.

Tributyrin is known to overcome the pharmacokinetic drawbacks of butyrate.  Because it is rapidly absorbed and chemically stable in plasma, tributyrin diffuses through biological membranes and is metabolized by intracellular lipases, releasing therapeutically effective butyrate over time directly into the cell. 

Ball-and-stick model of the butyrin molecule

Figure 3.  Ball-and-stick model of the tributyrin molecule, the triglyceride of butyric acid.  Source:  By Jynto (talk) – Own workThis chemical image was created with Discovery Studio Visualizer., CC0, https://commons.wikimedia.org/w/index.php?curid=20234384

The technique of attaching butyrate to a glycerol molecule turns the new molecule (tributyrin) into a fat. The attachment of a glycerol molecule to 3 butyric acid molecules is through an ester bond which can only be broken by a specific enzyme called pancreatic lipase.  

Pancreatic lipase is secreted from the pancreas into the small intestine (duodenum) and not in the stomach.  Because of this, tributyrin stays intact in the stomach but once it reaches the small intestine (duodenum), the 3 butyric acid molecules are released by the pancreatic lipase enzyme. 

After the pancreatic lipase action, two free butyric acid molecules and one monobutyrin molecule are formed where they are used in the intestine and taken up by the enterocytes. After transportation through the portal vein they are metabolized in the liver. 

chem formula

Figure 4.  Ester bond of glycerol and 3 butyric acid molecules.  (Source: Bioremediation of Fats and Oils)

The tributyrin form of butyrate ensures high bioavailability of butyrate in all the sections of the small intestine.  Because tributyrin is a delayed release source of butyrate, it achieves more sustained plasma levels. 

According the the U.S. Federal Drug Administration (FDA), tributyrin is a food substance affirmed as Generally Recognized As Safe (GRAS).  15

Multiple Health Benefits of Tributyrin 

Specific studies on tributyrin have demonstrated multiple benefits in a number of disease conditions by releasing therapeutically effective butyrate over time directly into the cell.  The advantage with tributyrin is that it has all the health benefits of butyrate, as evidenced above, as well as its own specific targeted health benefits.

Some of the more important and specific health benefits of tributyrin include:

  • Anticarcinogenic potential
    • Colon cancer
    • Leukemia
    • Melanoma
    • Liver cancer (apoptosis)
  • Alzheimer’s disease and Dementia
  • Antibiotic-associated diarrhea (AAD)
  • Lipopolysaccharide (LPS)-induced liver injury
  • Inflammation

Anticarcinogenic potential

In vitro and in vivo studies have shown that tributyrin acts on multiple anticancer cellular and molecular targets without affecting non-cancerous cells. The mechanisms of action of tributyrin as a anticarcinogenic agent include:  16

  • the induction of apoptosis
  • cell differentiation
  • the modulation of epigenetic mechanisms

Due to the minimum toxicity profile of tributyrin, it is an excellent candidate for combination therapy with other agents for the control of cancer. 

Colon cancer

Tributyrin was shown to be more potent in inhibiting growth and inducing cell differentiation than natural butyrate on growth, differentiation and vitamin D receptor expression in Caco-2 cells, a human colon cancer cell line.  17

Tributyrin provides a useful therapeutic approach in chemoprevention and treatment of colorectal cancer.   

In another in vitro study, tributyrin showed potent antiproliferative, proapoptotic and differentiation-inducing effects in neoplastic cells.  18

Leukemia

In this study monobutyrin (MB) and tributyrin (TB) were studied in vitro for their effects on inducing differentiation of human myeloid leukemia HL60 cells and murine erythroleukemia cells. On a molar basis TB was about 4-fold more potent than either BA or MB for inducing differentiation of HL60 cells. BA, MB, or TB induced erythroid differentiation of murine erythroleukemia cells.  19

Melanoma

A study from February 2011 sought to investigate a possibility to develop tributyrin emulsion as a potent anti-cancer agent against melanoma. Tributyrin emulsion was more potent than butyrate in inhibiting the growth of B16-F10 melanoma cells. Accumulation of cells at sub G(0)/G(1) phase and the DNA fragmentation induced by tributyrin emulsion treatment revealed that tributyrin emulsion inhibited the growth of B16-F10 cells by inducing apoptosis. Treatment with tributyrin emulsion suppressed the colony formation of melanoma cells in a dose-dependent manner.  20

The data from this study suggests that tributyrin emulsion may be developed as a potent anti-cancer agent against melanoma.

Liver cancer

Researchers in this study from November 1999 investigated whether butyrate could induce apoptosis in transformed human liver (Hep G2) cells. Hep G2 cells treated with butyrate displayed acetylated histones, increased DNA fragmentation and morphological features consistent with apoptosis. 

They also investigated whether butyrate present in tributyrin, a triacylglycerol more compatible for inclusion into colloidal lipid structures than butyrate, could also induce apoptosis in Hep G2 cells.

Tributyrin induced DNA fragmentation and morphological features characteristic of apoptotic cells in Hep G2 cells.

These results are a significant advance towards delivering butyrate via colloidal lipid particles to cancerous sites in vivo. This study showed that butyrate and tributyrin are potent apoptotic agents. 21

Alzheimer’s disease and Dementia

Recent research at MIT has determined that, in rodent models of Alzheimer’s dementia, the negative impact of amyloid beta exposure on neuronal function and new memory formation results largely from increased neuronal expression of an enzyme known as HDAC2 (histone deacetylase 2).

A study from March 2004 showed that tributyrin may have the most practical potential to inhibit HDAC by blunting microglial activation. Tributyrin is anti-inflammatory in primary, brain-derived microglial cells.  A blunting of microglial cytokine production might in itself have a favorable impact on progression of Alzheimer’s.  22  23  

Antibiotic-associated diarrhea (AAD)

In a recent study from November 2014, researchers hypothesized that antibiotic-induced changes in gut microbiota reduce butyrate production, varying genes involved with gut barrier integrity and water and electrolyte absorption, lending to AAD, and that simultaneous supplementation with the probiotic Lactobacillus GG  and/or tributyrin would prevent these changes.

Optimizing intestinal health with Lactobacillus GG and/or tributyrin may offer a preventative therapy for AAD.  24  Lipopolysaccharide (LPS)-induced liver injury

In this study from April 2015, researchers elucidated the protective effect of oral administration of tributyrin against LPS-mediated lipid metabolism disorder in rats.  Tributyrin suppresses lipopolysaccharide (LPS)-induced liver injury through attenuating nuclear factor-κB activity with an increased hepatoportal butyrate level.  25

Inflammation

Another study from May 2015 was carried out to investigate the effects of tributyrin (TB) on the growth performance, pro-inflammatory cytokines, intestinal morphology, energy status, disaccharidase activity, and antioxidative capacity of broilers challenged with lipopolysaccharide (LPS).

Taken together, these results suggest that the TB supplementation was able to reduce the release of pro-inflammatory cytokines and improve the energy status and anti-oxidative capacity in the small intestine of LPS-challenged broilers.  26

ELiE Health Solutions

Tributyrin is now available for purchase by consumers and professionals directly from ELiE Health Solutions as a product called BUTYCAPS.

ELiE Health Solutions, based in Sevilla, Spain, was formed through a project based on the science of the microbiota and probiotics.

ELiE Health Solutions is named after Elie Metchnikoff, famed microbiologist and the recipient of the 1908 Nobel Price in Physiology. A century ago he proposed the benefit of acid lactic bacteria to the human host and their role in health and longevity.

David Manrique, a pharmacist with ELiE Health Solutions describes the challenges of finding a more bio-available form of butyric acid:

“The challenge was to find a chemical form of enteric release of butyric acid, and also to ensure microencapsulated as slowly and delayed release possible. It has been a great innovative effort, but we are very satisfied with the results.”  27 

ELiE Health Solutions was successful in developing a delayed release form of butyric acid (tributyrin) using microencapsulation technology in their product BUTYCAPS.  The microencapsulation technology of BUTYCAPS allows a slower and gradual release along the intestine. 

BUTYCAPS contains 900 mg of Tributyrin equivalent to 787 mg of butyric acid in each sachet. Each box contains 30 sachets.  BUTYCAPS are non-chewable granules.

170126_3dbutycaps

Figure 5.  BUTYCAPS product from ELiE Health Solutions

BUTYCAPS can be purchased directly from ELiE Health Solutions. 

Figure 6.  Formulation process of microencapsulated tributyrin. (Source:  ELiE Health Solutions)

Resources:

Purchase BUTYCAPS

Cover photo:  Enterocytes were butyrate is taken up in the intestine (Source)

Polypodium leucotomos Extract Reduces Oxidative DNA Damage and Enhances DNA Repair

Polypodium leucatomos is an epiphytic fern native to tropical and subtropical regions of the Americas.  It’s alternative botanical name is Phlebodium aureum.

The common names for this fern include:

  • golden polypody
  • golden serpent fern
  • cabbage palm fern
  • gold-foot fern
  • hare-foot fern

Other common names in other languages include:

  • calaguala (Spanish language)
  • laua`e haole (Hawaiian)
  • samambaia (Portuguese)
  • hartassbräken (Swedish)

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Figure 1.  Polypodium leucotomos fern

Extracts from the Polypodium leucotomos fern have been used for centuries in South America and Spain, primarily for the treatment of:

  • psoriasis
  • various skin disorders
  • atopic dermatitis
  • vitiligo
  • sun protection from ultraviolet radiation

The phenolic components of Polypodium leucotomos extract include:  1

  • chlorogenic acid
  • coumaric acid
  • vanillic acid
  • caffeic
  • ferulic acid

Multiple Benefits From the Oral Supplementation of Polypodium leucotomos

A number of recent studies have demonstrated through their data that the oral administration of polypodium leucotomos postively effects health and affords the following photoprotective effects:  2

  • activates tumor suppressor p53
  • inhibits UV-induced Cox-2 expression
  • reduces inflammation
  • enhances the removal of UV-induced photoproducts, such as cyclobutane pyrimide dimers (CPDs)
  • reduces oxidative DNA damage and decreased UV-induced mutagenesis
  • reduces the number of 8-hydroxy-2’-deoxyguanosine-positive (8-OH-dG+) cells, which are markers of early DNA damage

Polypodium leucotomos Helps Prevent DNA Damage

Two studies from 2009 and 2010 suggest that Polypodium leucotomos helps prevent DNA damage before and during UV exposure. 3  4 

Oxidative damage of DNA has been implicated as a fundamental cause of the physiologic changes and degenerative diseases associated with aging.  When DNA is impacted by oxidative stress, the chemical 8-Oxo-2′-deoxyguanosine (8-oxo-dG) is produced as a byproduct.

Because 8-oxo-dG is a major product of DNA oxidation, concentrations of 8-oxo-dG within a cell is a ubiquitous marker and measurement of oxidative stress.

8-oxo-dG increases with age in DNA of mammalian tissues.  8-oxo-dG increases in both mitochonndrial DNA and nuclear DNA with age. 5

8-oxo-dG is a pre-mutagenic marker of oxidative damage to DNA and is caused by the UV-induced generation of reactive oxygen species. 8-oxo-dG positive cells were reduced by approximately 59% at 24 hours and by 79% at 48 hours in Polypodium leucotomos-treated animals compared to control animals.

These findings support the concept that Polypodium leucotomos reduces oxidative DNA damage.

Two weeks after UV exposure, mutations in Polypodium leucotomos-fed-mice were approximately 25% less than those from mice treated with UV alone.  6 

A clinical trial from 2010 found that a daily does of 240 mg of polypodium leucotomos by healthy volunteers aged 29 to 54 before UVA exposure decreased levels of a marker of DNA damage.  7 

Among the placebo volunteers a low dose of UV light produced a 217% increase in common DNA deletions.

Among the polypodium leucotomos supplemented volunteers showed a corresponding 84% decrease in common DNA deletions.  8 

When the UV exposure was increased the common DNA deletions increased by 760% for the placebo volunteers, whereas in the polypodium leucotomos volunteers there was only an increase of 61%.  9  

Polypodium Leucotomos Extract: A Photoprotective Anti Aging Oral Supplement

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

 

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”.

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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

AA/EPA Ratio: A Major Marker of Cellular Inflammation

Cellular or Chronic Inflammation

According to Life Extension® cellular or chronic low-level inflammation contributes to the pathogenesis of at least seven of the ten leading causes of mortality, which include:  1

  • heart disease
  • cancer
  • chronic lower respiratory disease
  • stroke
  • Alzheimer’s disease
  • diabetes
  • nephritis

There are two types of inflammation:

  • acute inflammation
  • chronic inflammation

Acute inflammation is a short term response to tissue injury that produces symptoms of pain.  Acute inflammation usually resolves rather quickly depending on the nature of the injury.

Chronic inflammation is usually triggered by cellular stress and dysfunction and plays a major role in the development of degenerative diseases and loss of normal functions. 

Chronic inflammation is silent in its nature and thus usually shows no signs of pain or at least acute pain.  Because it is below the perception of pain, it tends to have a very destructive power and often disrupts hormonal signaling at the cellular level.  This often leads to the following:

  • increased fat accumulation
  • acceleration of the development of chronic disease
  • decreased physical performance

Measuring Cellular or Chronic Inflammation

Even though cellular or chronic inflammation is silent (absent of pain signals), it can be measured with a number of medical tests.

The three most common tests for cellular inflammation include:

  • hs-C-reactive protein (hs-CRP)
  • Nuclear factor kappa-B (NF-kB)
  • AA/EPA Ratio

hs-C-reactive protein (hs-CRP)

hs-C-reactive protein (hs-CRP) is one of the earliest and often used marker of inflammation.  It is a very effective measure of cellular inflammation.  

hs-CRP is a protein that is synthesized in the liver in response to elevated levels of IL-6 in the blood.  Since hs-CRP is a long-lived protein in the blood, as opposed to others that have a short half life, it is easily measured. 

The two drawbacks to hs-CRP is that a slight bacterial infection can elevate its levels; and, it is a late downstream marker of cellular inflammation rather than an early warning sign.  2

Nuclear factor kappa-B (NF-kB)

Nuclear factor kappa-B (NF-kB) is important in the initiation of the inflammatory response. When cells are exposed to damage signals (such as TNF-α, IL-1β, IL-6 or oxidative stress), they activate NF-kB.  3 

The drawback to Nuclear factor kappa-B (NF-kB) is that their levels in the blood are very low and they have very short half-lives.  4

AA/EPA Ratio

The AA/EPA ratio in the blood is considered the best marker of cellular inflammation in the body.

The AA/EPA ratio is the ratio of two fatty acids in the blood, the omega-6 fatty acid arachidonic acid (AA) and the omega-3 fatty acid eicosapentaenoic acid (EPA). 

Focus on Omega-6 Fatty Acids/Arachidonic acid (AA) and Omega-3 Fatty Acids/Eicosapentaenoic acid (EPA)

Omega-6 Fatty Acids and Arachidonic acid (AA)

Arachidonic acid (AA) is a polyunsaturated omega-6 fatty acid.  It is either synthesized in the human body or obtained via the diet.  

AA is synthesized from the consumption of linoleic acid known as omega-6 fatty acids.   Dietary sources of omega-6 fatty acids include:

Plant based omega-6 fatty acids:

  • nuts
  • hulled sesame seeds
  • pumpkin seeds
  • sunflower seeds
  • almonds
  • cereals
  • durum wheat
  • whole-grain breads
  • grape seed oil
  • evening primrose oil
  • borage oil
  • blackcurrant seed oil
  • flax/linseed oil
  • rapeseed or canola oil
  • hemp oil
  • soybean oil
  • cottonseed oil
  • sunflower seed oil
  • corn oil
  • safflower oil
  • Salicornia oil
  • poppy seed oil
  • sunflower oil
  • Barbary Fig Seed Oil
  • wheat germ oil
  • cottonseed oil
  • walnut oil
  • sesame oil
  • rice bran oil
  • Argan oil
  • pistachio oil
  • peanut oil
  • olive oil (small amounts)

Animal based omega-6 fatty acids:

  • poultry
  • chicken fat
  • egg yolk
  • lard

Image result for omega 6

Figure 1.  Omega-6 Fatty Acid Food Sources

Arachidonic acid is also found in certain foods and can be consumed directly.  Arachidonic acid is found in the following foods:

  • meat
  • poultry
  • eggs

Image result for AA/EPA ratio

Figure 2.  Arachidonic acid in foods and their inflammatory cascade  (Source)

Even though a certain level of arachidonic acid is necessary in the body, an excess of AA in the blood is the building block of pro-inflammatory eicosanoids that stimulate cellular inflammation.

Ideally the AA levels in the blood should be between 7 and 9% of the total fatty acids.

Omega-3 Fatty Acids and Eicosapentaenoic acid (EPA)

Omega-3 fatty acids are polyunsaturated fatty acids (PUFAs).  They consist of:

  • alpha-linolenic acid (ALA); (found in plant oils)
  • eicosapentaenoic acid (EPA); (found in marine oils)
  • docosahexaenoic acid (DHA); (found in marine oils)

Alpha-linolenic acid (ALA) is converted into EPA and DHA in the body through desaturations (addition of a double bond) and elongation (addition of two carbon atoms) enzymes.  However, this process results in a very low ration of EPA and DHA. 

This means that even consuming large quantities of ALA, the body can only convert a relatively small amount into EPA and DHA, and only when there are sufficient enzymes.

Linoleic Acid (LA) (Omega-6 fatty acid) and ALA compete for the same elongase and desaturase enzymes in the synthesis of longer polyunsaturated fatty acids, such as AA and EPA.

The are two primary sources of omega-3 fatty acids, animal and plant sources. 

Marine animals such as fish and krill provide eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA).  Plant foods, such as flaxseed and chia seed provide alpha-linoleic acid (ALA).

Plant based omega-3 fatty acids:

  • Flaxseed/oil
  • Hemp seed/oil
  • Canola oil
  • Mustard oil
  • Algae oil
  • Chia seed
  • Chicken egg
  • Broccoli
  • Walnuts
  • Soybeans
  • Microalgae (oil) (Crypthecodinium cohnii, Schizochytrium, brown algae and Nannochloropsis)
  • Perilla (Perilla frutescens)
  • Edible seaweeds (e.g., Wakame, Hijiki, Kombu)
  • Camelina  5
  • Lingon Berry  (Vaccinium vitis-idaea)
  • Purslane  (Portulaca oleracea)
  • Kiwifruit seed oil  (Actinidia deliciosa)

Animal based omega-3 fatty acids:

  • Fish (oily fish)
  • Fish oil
  • Krill oil
  • Cod Liver oil
  • Greenshell/lipped mussels
  • Fish roe (eggs) (Both red and black caviar)
  • Turkey
  • Grass fed lean red meat (The omega-6:omega-3 ratio of grass-fed beef is about 2:1, making it a more useful source of omega-3 than grain-fed beef, which usually has a ratio of 4:1.)

EPA is a very powerful anti-inflammatory mediator and also acts as a competitive inhibitor of AA for the enzymes necessary for the production of inflammatory eicosanoids.

Since the AA/EPA ratio provides a specific indicator of the balance between omega-6 and omega-3 fatty acids in circulation, when this ratio is higher, there is preferred incorporation of AA into membranes over EPA, leading to a pro-inflammatory environment.  6

The ideal AA/EPA ratio is between 1.5 and 3 which is often found in the Japanese population.  In the American population the AA/EPA ratio is often found around 15.

Image result for AA/EPA ratio

Figure 3.  Typical AA/EPA Ratios  (Source)

The higher the AA/EPA ratio, the higher are the levels of cellular inflammation.  The Table below lists the ranges of AA/EPA and the corresponding cellular inflammation and future states of wellness:

AA/EPA Ranges Cellular Inflammation Future state of wellness
1.5 to 3 Low Excellent
3 to 6 Moderate Good
7 to 15 Elevated Moderate
> than 15 High Poor

(Source)

The higher the levels of cellular inflammation, the more likely the future development of chronic disease will be accelerated. Populations with an AA/EPA ratio greater than 12 are often associated with chronic diseases.  7 

Image result for AA/EPA ratio

Figure 4.  AA to EPA Ratio – Biomarker of Inflammatory Status  (Source)

How to Reduce and Improve the AA/EPA Ratio Through Dietary Methods

The AA/EPA ratio can be modulated strictly through diet, and not through pharmaceuticals or nutraceuticals.

According to Dr. Barry Sears, a leading authority on the dietary control of hormonal and inflammatory responses and considered the founder of anti-inflammatory nutrition, he states that:

“If the AA levels in the blood are greater than 9% of the total fatty acids, then a more restrictive anti-inflammatory diet is required to lower insulin and a greater restriction of omega-6 fatty intake is also required. 

If the EPA levels are less than 4% of the total fatty acids, then greater consumption of fatty fish or omega-3 fatty concentrates is required.”  8 

Significant changes to the AA/EPA ratio can occur in 60 days of dietary changes, since the ratio reflects the previous 30 days of dietary intake.

The fastest way to reduce the AA/EPA ratio is to increase the intake of high-purity omega-3 fatty acid concentrates rich in EPA.  The other way to reduce the AA/EPA ratio is to reduce the consumption of arachidonic acid (AA) and omega-6 fatty acids (LA). 

Practicing both dietary changes (increasing EPA and reducing AA and LA consumption) is the primary method to reduce the AA/EPA ratio.

The Table below lists the EPA and DHA levels in marine animals and can be used as a guide to increase consumption of EPA: 

EPA and DHA Levels in Marine Animals

Fish Species and DescriptionDHA per 100 gEPA per 100 gDHA+EPA per 100 gDHA+EPA per 85 g (3 oz.)
Crustaceans, crab, Alaska king, cooked, moist heat0.1180.2950.4130.351
Crustaceans, crab, blue, cooked, moist heat0.2310.2430.4740.403
Crustaceans, crab, Dungeness, cooked, moist heat0.1130.2810.3940.335
Crustaceans, crab, queen, cooked, moist heat0.1450.3320.4770.405
Crustaceans, crayfish, mixed species, farmed, cooked, moist heat0.0380.1240.1620.138
Crustaceans, crayfish, mixed species, wild, cooked, moist heat0.0470.1190.1660.141
Crustaceans, lobster, northern, cooked, moist heat0.0310.0530.0840.071
Crustaceans, shrimp, mixed species, cooked, moist heat0.1440.1710.3150.268
Crustaceans, spiny lobster, mixed species, cooked, moist heat0.1390.3410.480.408
Fish, anchovy, European, raw0.9110.5381.4491.232
Fish, anchovy, European, canned in oil, drained solids1.2920.7632.0551.747
Fish, bass, freshwater, mixed species, cooked, dry heat0.4580.3050.7630.649
Fish, bass, striped, cooked, dry heat0.750.2170.9670.822
Fish, bluefish, cooked, dry heat0.6650.3230.9880.84
Fish, turbot, cooked, dry heat0.1230.090.2130.181
Fish, carp, cooked, dry heat0.1460.3050.4510.383
Fish, catfish, channel, farmed, cooked, dry heat0.1280.0490.1770.15
Fish, catfish, channel, wild, cooked, dry heat0.1370.10.2370.201
Fish, caviar, black and red, granular3.82.7416.5415.56
Fish, cod, Atlantic, cooked, dry heat0.1540.0040.1580.134
Fish, cod, Pacific, cooked, dry heat0.1730.1030.2760.235
Fish, croaker, Atlantic, raw0.0970.1230.220.187
Fish, dolphin fish, cooked, dry heat0.1130.0260.1390.118
Fish, drum, freshwater, cooked, dry heat0.3680.2950.6630.564
Fish, eel, mixed species, cooked, dry heat0.0810.1080.1890.161
Fish, fish portions and sticks, frozen, preheated0.1280.0860.2140.182
Fish, flatfish (flounder and sole species), cooked, dry heat0.2580.2430.5010.426
Fish, grouper, mixed species, cooked, dry heat0.2130.0350.2480.211
Fish, haddock, cooked, dry heat0.1620.0760.2380.202
Fish, halibut, Atlantic and Pacific, cooked, dry heat0.3740.0910.4650.395
Fish, halibut, Greenland, cooked, dry heat0.5040.6741.1781.001
Fish, herring, Atlantic, cooked, dry heat1.1050.9092.0141.712
Fish, herring, Atlantic, kippered1.1790.972.1491.827
Fish, herring, Pacific, cooked, dry heat0.8831.2422.1251.806
Fish, lingcod, cooked, dry heat0.130.1330.2630.224
Fish, mackerel, Atlantic, cooked, dry heat0.6990.5041.2031.023
Fish, mackerel, king, cooked, dry heat0.2270.1740.4010.341
Fish, mackerel, Pacific and jack, mixed species, cooked, dry heat1.1950.6531.8481.571
Fish, mackerel, Spanish, cooked, dry heat0.9520.2941.2461.059
Fish, mullet, striped, cooked, dry heat0.1480.180.3280.279
Fish, ocean perch, Atlantic, cooked, dry heat0.2710.1030.3740.318
Fish, perch, mixed species, cooked, dry heat0.2230.1010.3240.275
Fish, pike, northern, cooked, dry heat0.0950.0420.1370.116
Fish, pike, walleye, cooked, dry heat0.2880.110.3980.338
Fish, pollock, Atlantic, cooked, dry heat0.4510.0910.5420.461
Fish, pompano, Florida, cooked, dry heat??????0.620 est
Fish, rockfish, Pacific, mixed species, cooked, dry heat0.2620.1810.4430.377
Fish, roe, mixed species, cooked, dry heat1.7471.263.0072.556
Fish, roe, mixed species, raw1.3630.9832.3461.994
Fish, roughy, orange, raw00.0010.0010.001
Fish, sablefish, cooked, dry heat0.920.8671.7871.519
Fish, sablefish, smoked0.9450.8911.8361.561
Fish, salmon, Atlantic, farmed, cooked, dry heat1.4570.692.1471.825
Fish, salmon, Atlantic, wild, cooked, dry heat1.4290.4111.841.564
Fish, salmon, Chinook, cooked, dry heat0.7271.011.7371.476
Fish, salmon, chum, cooked, dry heat0.5050.2990.8040.683
Fish, salmon, chum, drained solids with bone0.7020.4731.1750.999
Fish, salmon, coho, farmed, cooked, dry heat0.8710.4081.2791.087
Fish, salmon, coho, wild, cooked, dry heat0.6580.4011.0590.9
Fish, salmon, pink, cooked, dry heat0.7510.5371.2881.095
Fish, salmon, sockeye, cooked, dry heat0.70.531.231.046
Fish, sardine, Atlantic, canned in oil, drained solids with bone0.5090.4730.9820.835
Fish, scup, raw (Porgy—assigned to low omega-3 group)no datano datano datano data
Fish, sea bass, mixed species, cooked, dry heat0.5560.2060.7620.648
Fish, sea trout, mixed species, cooked, dry heat0.2650.2110.4760.405
Fish, shad, American, raw1.3211.0862.4072.046
Fish, shark, mixed species, raw0.5270.3160.8430.717
Fish, sheepshead, cooked, dry heat0.1070.0830.190.162
Fish, smelt, rainbow, cooked, dry heat0.5360.3530.8890.756
Fish, snapper, mixed species, cooked, dry heat0.2730.0480.3210.273
Fish, spot, cooked, dry heat0.5260.2820.8080.687
Fish, sturgeon, mixed species, cooked, dry heat0.1190.2490.3680.313
Fish, sucker, white, cooked, dry heat0.3710.2440.6150.523
Fish, sunfish, pumpkin seed, cooked, dry heat0.0920.0470.1390.118
Fish, swordfish, cooked, dry heat0.6810.1380.8190.696
Fish, tilefish, cooked, dry heat0.7330.1720.9050.769
Fish, trout, mixed species, cooked, dry heat0.6770.2590.9360.796
Fish, trout, rainbow, farmed, cooked, dry heat0.820.3341.1540.981
Fish, trout, rainbow, wild, cooked, dry heat0.520.4680.9880.84
Fish, tuna, fresh, bluefin, cooked, dry heat1.1410.3631.5041.278
Fish, tuna, light, canned in oil, drained solids0.1010.0270.1280.109
Fish, tuna, light, canned in water, drained solids0.2230.0470.270.23
Fish, tuna, skipjack, fresh, cooked, dry heat0.2370.0910.3280.279
Fish, tuna, white, canned in water, drained solids0.6290.2330.8620.733
Fish, tuna, yellowfin, fresh, cooked, dry heat0.2320.0470.2790.237
Fish, whitefish, mixed species, cooked, dry heat1.2060.4061.6121.37
Fish, whiting, mixed species, cooked, dry heat0.2350.2830.5180.44
Fish, wolffish, Atlantic, cooked, dry heat0.4050.3930.7980.678
Frog legs, raw0.0340.02
Mollusks, abalone, mixed species, raw00.0490.0490.042
Mollusks, clam, mixed species, cooked, moist heat0.1460.1380.2840.241
Mollusks, conch, baked or broiled0.0720.0480.120.102
Mollusks, cuttlefish, mixed species, cooked, moist heat0.1320.0780.210.179
Mollusks, mussel, blue, cooked, moist heat0.5060.2760.7820.665
Mollusks, octopus, common, cooked, moist heat0.1620.1520.3140.267
Mollusks, oyster, eastern, farmed, cooked, dry heat0.2110.2290.440.374
Mollusks, oyster, eastern, wild, cooked, dry heat0.2910.260.5510.468
Mollusks, oyster, Pacific, cooked, moist heat0.50.8761.3761.17
Mollusks, scallop, mixed species, cooked, breaded and fried0.1030.0860.180.161
Mollusks, whelk, unspecified, cooked, moist heat0.0120.0080.020.017

The Table below lists the omega-3 fatty acids in various foods:

Omega-3 in Certain Various Foods

CategoryFoodServing SizeOmega-3 fatty acids (g)
FishBluefish, fresh and frozen, cooked4 oz1.7
FishCod, fresh and frozen4 oz0.6
FishCrab, soft shell, cooked4 oz0.6
FishLobster, cooked4 oz0.12
FishMackerel, canned, drained4 oz2.2
FishSalmon, canned, drained4 oz2.2
FishSalmon, wild, raw4 oz (113g)2.3
FishSardines, canned in oil, drained4 oz1.8
FishScallops, Maine, fresh and frozen, cooked4 oz0.5
FishSmelt, rainbow4 oz0.5
FishSwordfish, fresh and frozen, cooked4 oz1.7
FishTuna, canned in oil, drained4 oz0.2
FishTrout, rainbow100 g0.986
FishBass, freshwater100 g0.79
FishDemersal fish100 g0.388
FishFlatfish, flounder and sole 100 g0.253
FishHalibut100 g0.522
FishPelagic fish3100 g0.989
FishTuna, bluefin 100 g1.298
FishCod, Atlantic100 g0.195
FishPollock, Atlantic 100 g0.443
FishCrustaceans, shrimp 100 g0.54
FishMollusks, mussel 100 g0.483
FishTuna, canned in water, drained4 oz0.3
Grains & BeansMatpe (Vigna mungo bean), boiled1 cup0.6
Grains & BeansPeanut, All types,raw1/2 cupTrace
Grains & BeansSoybeans, dried, cooked1/2 cup0.5
Grains & BeansTofu, regular4 oz0.3
Grains & BeansNatt ō , regular1 cup1.3
Grains & BeansChickpeas, mature seeds, cooked, boiled, without salt1 cup0.07
Green leafy vegetablesArugula raw1 cup34
Green leafy vegetablesGreen leaf lettuce, fresh, raw1 cupTrace
Green leafy vegetablesRed leaf lettuce, fresh, raw1 cupTrace
Green leafy vegetablesBoston lettuce or Bibb lettuce, fresh, raw1 cupTrace
Green leafy vegetablesBrussels sprouts cooked1 cup270
Green leafy vegetablesCabbage red, raw1 cup40
Green leafy vegetablesChinese cabbage cooked, boiled, drained, without salt1 cup69.7
Green leafy vegetablesChard, cooked, boiled, drained, without salt1 cup5.3
Green leafy vegetablesSauerkraut, canned, low sodium1 cup36
Green leafy vegetablesSpinach, cooked, boiled, drained, without salt1 cup166
Green leafy vegetablesTurnip greens, cooked1/2 cupTrace
Green leafy vegetablesDandelion greens, cooked1/2 cup0.1
Green leafy vegetablesKale, cooked1/2 cup0.1
Green leafy vegetablesKohlrabi raw1 cup35
Green leafy vegetablesBeet greens, cooked1/2 cupTrace
Green leafy vegetablesCollard greens, cooked, boiled, drained, without salt1 cup177
Green leafy vegetablesMustard greens, cooked, boiled, drained, without salt1 cup30.8
MeatsPoultry meats3100 g0.121
MeatsChicken, with skin100 g0.19
MeatsChicken, without skin 100 g0.08
MeatsTurkey with skin 100 g0.15
MeatsTurkey, without skin100 g0.06
MeatsPig meats100 g0.065
MeatsPork loin, without fat100 g0.024
MeatsPork loin, without fat100 g0.02
MeatsPork, with fat100 g0.09
MeatsEggs100 g0.081
MeatsBovine meats100 g0.122
MeatsBeef rib eye100 g0.029
MeatsBeef rib eye100 g0.01
MeatsBeef sirloin100 g0.05
MeatsLamb loin chop100 g0.076
MeatsLamb steak leg100 g0.292
Nuts & SeedsAlmonds, dry roasted1 oz0.002
Nuts & SeedsCashews1 oz0.017
Nuts & SeedsChia seeds1 oz4.915
Nuts & SeedsCoconut, raw1 oztrace
Nuts & SeedsFlax seeds1 oz6.388
Nuts & SeedsHazelnuts, filberts1 oz0.024
Nuts & SeedsPecans1 oz0.276
Nuts & SeedsPistachios, raw1 oz0.071
Nuts & SeedsPoppy seed1 oz0.076
Nuts & SeedsPumpkin seeds, whole, roasted, without salt1 oz0.021
Nuts & SeedsSesame seeds, whole, dried1 oz0.105
Nuts & SeedsSunflower seeds, kernels, dried1 oz0.021
Nuts & SeedsWalnuts1 oz2.542
Nuts & SeedsSacha Inchi seeds1 oz4.771
Nuts & SeedsLentils, mature seeds, cooked, boiled, without salt1 oz10.4
OlisAvocado Oil0.14
OlisButter
OlisCanola oil1 Tbsp1.3
OlisCoconut oil
OlisCod liver oil1 Tbsp2.8
OlisCorn oil
OlisCotton seed
OlisFlax seed oil1 Tbsp6.9
OlisGhee
OlisGrape seed
OlisLard
OlisOlive oil1 Tbsp0.1
OlisPalm oil (Hydrogenated)
OlisPeanut oil1 TbspTrace
OlisSardine oil1 Tbsp3.7
OlisSoybean oil, (Unhydrogenated)1 Tbsp0.9
OlisTallow (Grain Fed)0.002
OlisTallow (Grass Fed)0.008
OlisWalnut oil1 Tbsp (15 g)1.4
Pumpkin & squashesButternut squash, Squash, winter, butternut, cooked, baked, without salt1 cup0.0492
Pumpkin & squashesZucchini, Squash, summer, zucchini, includes skin, raw1 cup0.0583
Pumpkin & squashesAcorn squash, Squash, winter, acorn, cooked, baked, without salt1 cup0.0759
Pumpkin & squashesTomatoes, Tomatoes, red, ripe, raw1 cup0.045
Root vegetablesCarrots, raw1 cup0.0026
Root vegetablesBeets, raw1 cup0.0068
Root vegetablesParsley, raw1 cup0.0048
Root vegetablesTurnips, raw1 cup0.052

A guideline (based on an Italian study) provided by Dr. Barry Sears, indicates (in the Table below) how much EPA and DHA to consume to reduce the AA/EPA ratio.

Grams of EPA and DHA supplemented per day AA/EPA Ratio
0 12.1
0.8 4.7
2.5 2.6
5.0 1.3
7.5 1.2

This data indicates that a daily dosage of EPA and DHA of 2.5 grams was sufficient to bring the AA/EPA ratio into the desired range for excellent wellness for these healthy individuals. This level of EPA and DHA recommendation correlates well with an Italian study that demonstrated in patients with various chronic diseases having an elevated AA/EPA ratio (>15) lowered their elevated AA/EPA ratio to approximately 5 with daily supplementation of 2.5 grams of EPA and DHA (1). This is also indicative that a person with an existing chronic disease may need greater amounts of EPA and DHA to get them into an excellent wellness range compared to a healthy individual.  9

Even though these are guidelines for daily EPA and DHA supplementation, Dr. Barry Sears recommends that an individual test for the AA/EPA ratio every six to twelve months in order to optimize the AA/EPA ratio.  

Chinese Succulent Plant Shilianhua Regulates Glucose Metabolism and Insulin Sensitivity by Inhibiting GSK-3β and NF-κB

There are a number of recognized ‘blue zones’ around the world which are considered longevity hotspots where a certain amount of the population have long average life spans and a high number of centenarians.

One such blue zone is found in Western China on the slopes of the Himalayas called Bama Yao Autonomous County (aka Bama County):

Image result for Bama Yao Autonomous County

Figure 1.  Bama Yao Autonomous County

Bama County is a county in Guangxi, China and is under the administration of Hechi City.

Image result for Bama Yao Autonomous County

Figure 2.  Location of Bama Yao Autonomous County

Out of an approximate population of 230,000, Bama County has at least 79 men and women over 100 years old and still very physically active.  Their ratio of 3.52 centenarians per 10,000 people is the highest found anywhere in the world.  It is claimed that the residents of Bama County have the longest average life span of any other country in the world.

Centenarians say age is just a number

Figure 3.  Centenarian resident of Bama County

Among the many environmental factors attributed to blue zones, certain foods and diet play a significant role.  In the case of Bama County, a specific and unique food has been found to play a key role in the longevity of their residents.

A majority of the residents of Bama County consume daily a plant food called Shilianhua or “rock lotus’.  The botanical name of shilianhua is Sinocrassula and is a genus of succulent, subtropical plants of the family Crassulaceae.

The name “Sinocrassula” means “Chinese crassula” and is grown primarily in the province of Yunnan in the south of China, and also from the north of Burma. It grows at an altitude between 2,500 and 2,700 meters and typically blooms from June through August in the Northern Hemisphere. 

Image result for Sinocrassula indica

Figure 4.  Sinocrassula indica, aka Shilianhua or rock lotus

The Pennington Biomedical Research Center, Louisiana State University System; and the Medicinal Plant Research Laboratory, School of Renewable Natural Resources, Louisiana State University Agricultural Center in Baton Rouge, Louisiana, published on 7 April 2009 in the American Journal of Physiology-Endocrinology and Metabolism a paper which examined the anti-diabetes effects of extracts of Shilianhua (SLH).  1

In this study, the researchers isolated the bioactive ingredients of SLH and explored the mechanisms of action of its F100 fraction. The result of the study suggests that the F100 fraction of SLH exhibited a significant activity in enhancing insulin sensitivity in mice.

After treatment with SLH for 8 weeks, fasting insulin and fasting blood glucose (FBG) were reduced by 43 and 27%, respectively.

Glucose consumption was induced significantly by F100 in 3T3-L1 adipocytes, L6 myotubes, and H4IIE hepatocytes in the absence of insulin. F100 also increased insulin-stimulated glucose consumption in L6 myotubes and H4IIE hepatocytes. It increased insulin-independent glucose uptake in 3T3-L1 adipocytes and insulin-dependent glucose uptake in L6 cells. The glucose transporter-1 (GLUT1) protein was induced in 3T3-L1 cells, and the GLUT4 protein was induced in L6 cells by F100.

The data suggest that F100 can act in an insulin- independent manner to stimulate glucose utilization.  F100 may use the insulin-signaling pathway to enhance the glucose consumption.

These results suggest that F100 induces glucose consumption in adipocytes, muscle cells, and hepatocytes in a dose-dependent manner. It may promote insulin activity in cell type-dependent manner (myotubes and hepatocytes). 

An external file that holds a picture, illustration, etc. Object name is zh10070956870005.jpg

Figure 5.  Effects of F100 in the KK.Cg-Ay/+ diabetic mice. A: effects of F100 on body weight, fat content, food intake, and serum insulin of KK.Cg-Ay/+ mice (n = 9). B: effect of F100 on fasting blood glucose (FBG) of the mice. C: effects of F100 on insulin tolerance of the mice (n = 9). AUC, area under the curve in the insulin tolerance test. Compared with control: *P < 0.05.  (Source)

SLH’s significant activity in enhancing insulin sensitivity in mice may be related to the inhibition by the F100 fraction in SLH of:

  • Glycogen Synthase Kinase-3 Enzyme (GSK-3) (specifcially  (GSK-3β)
  • Nuclear factor kappa-light-chain-enhancer of activated B cells  (NF-κB)

Glycogen Synthase Kinase-3 Enzyme (GSK-3)

Glycogen Synthase Kinase-3 Enzyme (GSK-3) is an enzyme in the body that, when normally activated, is part of the system regulating glucose metabolism.

However, when GSK-3 is overly and excessively activated, it tends to damage cellular structures.  Excessively activated GSK-3 can result in the following health issues in the body:  2 3 4

  • Accelerates aging in heart and muscle
  • Accelerates aging in the skeletal system
  • Accelerates aging in the stomach and liver
  • Develops type II diabetes
  • Develops Alzheimer’s disease  5
  • Impairs autophagy which clears toxic debris inside cells
  • Increases pro-inflammatory cytokines

Glycogen Synthase Kinase-3 Enzyme (GSK-3) Contributes to Alzheimer’s disease

The structural changes and defects that occur in the aging brain which develops into dementia and eventually Alzheimer’s disease include accumulation of beta amyloid plaque and damaged tau proteins.  Both of these results in neurofibrillary tangles which lead to neuron death.

Increased or aberrant over-expressive activity of the GSK-3 enzyme is a contributing factor in these structural changes.

Excessive GSK-3 damages (through the process of the hyperphosphorylation of tau proteins) tau proteins and is thought to directly promote amyloid beta production which leads to neurofibrillary tangles.  6

As mentioned, GSK-3 normally regulates glucose/insulin metabolism.  However, excessive GSK-3 may increase the development of Type II diabetes with glucose impairment and insulin resistance.  It is clear that Type II diabetes increases accumulations of beta amyloid and damaged tau proteins.  7

Because of this correlation, Alzheimer’s disease is often called Type III diabetes.

This conclusion lead to the Alzheimer’s strategy of inhibiting GSK-3 as a means to effectively lower blood glucose, while increasing insulin sensitivity.  8

GSK-3 Inhibitors

Targeted inhibition of GSK-3 may have therapeutic effects with regards to mild cognitive impairment and dementia (including Alzheimer’s disease).  The identified GSK-3 inhibitors are of diverse chemotypes and mechanisms of action, which include inhibitors isolated from natural sources, cations (minerals), and synthetic small molecules.

Shilianhua as a GSK-3 Inhibitor

GSK-3 inhibitors have been reported to improve insulin sensitivity in cellular and animal models.  9  GSK-3β may be a target of F100 in insulin sensitization.

The inhibition of GSK-3 leads to an increase in glycogen synthesis, which promotes insulin sensitivity. The activation of GSK-3 leads to reduction in glycogen synthesis and decrease in insulin sensitivity.

In response to insulin, the enzyme activity of GSK-3 is inhibited through Akt-mediated phosphorylation. The researchers suggested that this inhibitory mechanism may be used by F100 to stimulate glucose uptake in the cellular models and increase insulin sensitivity in mice.

Nuclear factor kappa-light-chain-enhancer of activated B cells  (NF-κB)

NF-κB is a protein complex that controls transcription of DNA, cytokine production and cell survival. NF-κB is found in almost all animal cell types and is involved in cellular responses to stimuli such as stress, cytokines, free radicals, heavy metals, ultraviolet irradiation, oxidized LDL, and bacterial or viral antigens.

NF-κB has long been considered a prototypical pro-inflammatory signaling pathway, largely based on the activation of NF-κB by pro-inflammatory cytokines such as interleukin 1 (IL-1) and tumor necrosis factor α (TNFα), and the role of NF-κB in the expression of other pro-inflammatory genes including cytokines, chemokines, and adhesion molecules

NF-κB is found to be chronically active in many inflammatory diseases, such as:

  • inflammatory bowel disease
  • arthritis
  • sepsis
  • gastritis
  • asthma
  • atherosclerosis

NF-κB has long been considered the “holy grail” as a target for new anti-inflammatory substances, both nutraceutical and pharmaceutical.

In this study the researchers found that NF-κB was strongly inhibited by the F100 fraction in SLH.  Inhibition of inflammation may also contribute to the insulin sensitization by F100. In response to F100, the LPS-induced cytokine (TNFα and MCP-1) expression was reduced in RAW 264.7 macrophages.

The NF-κB inhibition may be a result of GSK-3β suppression by F100.

In conclusion, the researchers stated:

“In summary, we conclude that F100 is a bioactive component in SLH and able to regulate glucose metabolism and insulin sensitivity in mice and in cells. The data suggest that the activity of F100 may be related to the inhibition of GSK-3β. The inhibition may improve insulin signaling in cell. Indirectly, F100 may protect insulin sensitivity by inhibition of NF-κB activity.”  10

U.S. Patents on Shilianhua

Two U.S. Patents have been filed on the medicinal use of Shilianhua, one on June 5, 1999 and the other on October 5, 2006:

US 5911993 A  Homeopathic antidiabetic treatment

A highly effective pure, natural, ingestible antidiabetic may be made from Shilianhua (Echevaria glauca, Sinocrassula berger, Crassulaceae) by washing leaves and/or stems of the Shilianhua plant, crushing them in a grinder, breaking the cell walls to form a filterable material, filtering the material to produce a filtrate, and decompressing and concentrating the filtrate to produce a concentrated solution.

Treatment of, or to prevent, diabetes by lowering blood sugar at least 10% (e. g. about 50%) is practiced by daily administration of about 50-100 mg of powdered extract of Echevaria glauca, Sinocrassula berger, Crassulaceae, or about 20-40 mg of concentrated powdered extract of Echevaria glauca, Sinocrassula berger, Crassulaceae.
WO 2006105407 A1  Medical uses of shilianhua

Shilianhua (SLH) extract has been discovered to display bioactivity in the regulation of fatty acid and glucose metabolism, and in inhibition of an inflammatory response. In addition, an active fraction of SLH extract has been characterized. An active SLH extract protected against insulin resistance through multiple mechanisms, including inhibition of IKK/NF-κB, stimulation of adiponectin secretion, promotion of fatty acid oxidation, and activation of p38.

SLH can be used in the prevention and treatment of diseases in which insulin resistance plays a major role, which includes hyperglycemia, cardiovascular diseases (such as hypertension, heart disease), stroke, renal failure, blindness, and non-traumatic limb amputation. SLH can be used to treat obesity and hyperlipidemia-related diseases by promotion of fatty acid oxidation and energy expenditure. SLH extracts may be used for prevention and treatment of inflammation and oxidative stress, and other diseases in which NF-κB plays a major role, such as arthritis, aging and cancer.  

Roe (eggs) of Marine Animals is the Best Natural Source of Omega-3 Fatty Acids

A study published on 7 August 2009 in the European Journal of Lipid Science and Technology found that the roe of marine animals is the best dietary source of omega-3 fatty acids, particularly the two types of omega-3 fatty acids:  1

  • Eicosapentaenoic acids (EPA)
  • Docosahexaenoic acids (DHA)

Researchers at the University of Almeria (UAL) analyzed the eggs, or roe, of 15 marine animals, and found all of these contained high levels of these omega-3 fatty acids, which are essential to the human body.  They showed that omega-3 fatty acids are present in all fish roe, but especially in the eggs of :

  • Atlantic bonito (Sarda sarda)
  • Mackerel (Scomber scombrus)
  • Squid (Loligo vulgaris)
  • Cuttlefish (Sepia sp.)
  • Lumpsucker (Cyclopterus lumpus)
  • European hake (Merluccius merluccius)
  • Salmon (Salmo salar)
  • Atlantic mackerel (Scomber scombrus) (gonads of male)

They also found that the three best dietary source of omega-3 fatty acids are found in the roe of:

  • European hake (Merluccius merluccius)
  • Lumpsucker (Cyclopterus lumpus)
  • Salmon (Salmo salar)

The roe of these three fish reached EPA + DHA amounts higher than 30% of their total fatty acid content.

José Luis Guil Guerrero, director of this study and a researcher in the Food Technology Department of the UAL, stated:

“We have classified these eggs as unequivocal sources of Omega 3, and have proven that this appears at high concentrations in all the species studies.”

According to a 2005 analysis from the United States Department of Agriculture (USDA), both red and black fish roe (caviar) contains the following grams of DHA and EPA:  2

DHA/100 grams                         3,800 grams  (58%)
EPA/100 grams                          2,741 grams  (42%)
DHA+EPA/100 grams                 6,541 grams  (100%)
DHA+EPA/85 grams (3 oz.)         5,560 grams

Roe or hard roe is the fully ripe internal egg masses in the ovaries, or the released external egg masses of fish.  There are usually two types of roe:

  • Red roe
  • Black roe

Red roe

Red roe is found from primarily Pacific, Atlantic and river species of salmon.  In Japan, there are a number of varieties of red roe and include these three:

  • Masago is roe from the capelin fish.  It is very small in size and has a orange color
  • Tobiko is roe from the flying fish. It has a red-orange color, a mild smoky or salty taste, and a crunchy texture
  • Ikura is roe from salmon.  It is a reddish orange color and larger in size than Tobiko

All three types of red roe are most widely known for its use in creating certain types of sushi.

Black roe

Black roe or caviar (Persian: خاویار‎, translit. Khāviyār‎) is a delicacy consisting of salt-cured fish-eggs of the Acipenseridae family. Traditionally, the term caviar refers only to roe from wild sturgeon in the Caspian Sea and Black Sea. 

There are a number of varieties of black roe from these areas:

  • Beluga
  • Ossetra
  • Sevruga  

Photographs of various Roe varieties

Figure 1.  Tobiko

Figure 2.  Masago

Figure 3.  Salmon roe

Figure 4.  Beluga

Figure 5.  Ossetra

Figure 6.  Sevruga

Delaying the Chronological Aging of the Yeast Saccharomyces cerevisiae by Six Plant Extracts

Researchers from Concordia University in Montreal, Quebec, Canada, in collaboration with the Quebec-based biotech company Idunn Technologies, published a study in the Journal Oncotarget on 29 March 2016, describing their discovery of six plant extracts that increase yeast chronological lifespan to a significantly greater extent than any of the presently known longevity-extending chemical compounds.  1

For the study, the researchers examined many plant extracts that would increase the chronological lifespan of yeast.  They finally found and used 37 plant extracts for this study.  These plant extracts are listed in the Table 1 below:

Table 1: List of plant extracts that have was used in this study

Abbreviated nameBotanical namePlant part used
PE1Echinacea purpureaWhole plant
PE2Astragalus membranaceousRoot
PE3Rhodiola rosea L.Root
PE4Cimicifuga racemosaRoot and rhizome
PE5Valeriana officinalis L.Root
PE6Passiflora incarnate L.Whole plant
PE7Polygonum cuspidatumRoot and rhizome
PE8Ginkgo bilobaLeaf
PE9Zingiber officinale RoscoeRhizome
PE10Theobroma cacao L.Cacao nibs
PE11Camellia sinensis L. KuntzeLeaf
PE12Apium graveolens L.Seed
PE13Scutellaria baicalensisRoot
PE14Euterpe oleraceaFruit
PE15Withania somniferaRoot and leaf
PE16Phyllanthus emblicaFruit
PE17Camellia sinensisLeaf
PE18Pueraria lobataRoot
PE19Silybum marianumSeed
PE20Eleutherococcus senticosusRoot and stem
PE21Salix albaBark
PE22Glycine max L.Bean
PE24Calendula officinalisFlower
PE25Salvia miltiorrhizaRoot
PE27Panax quinquefoliumRoot
PE28Harpagophytum procumbensRoot
PE29Olea europaea L.Leaf
PE30Gentiana luteaRoot
PE31Piper nigrumFruit
PE32Aesculus hippocastanumSeed
PE33Mallus pumila Mill.Fruit
PE34Fragaria spp.Fruit
PE35Ribes nigrumLeaf
PE36Dioscorea oppositaRoot
PE37Cinnamomum verumBark

Table source:  Discovery of plant extracts that greatly delay yeast chronological aging and have different effects on longevity-defining cellular processes

The means by which these six plant extracts (PEs) delays the onset and decreases the rate of yeast chronological aging is by eliciting a hormetic stress response. The budding yeast Saccharomyces cerevisiae is a beneficial model organism for the discovery of genes, signaling pathways and chemical compounds that slow cellular and organismal aging in eukaryotes across phyla.  Yeast was chosen in this study because aging progresses similarly in both yeast and humans.

The six PEs that were identified include:  2

  • Black Cohosh (Cimicifuga racemosa) (PE4)
  • Valerian  (Valeriana officinalis L.)  (PE5)
  • Passion Flower  (Passiflora incarnata L.)  (PE6)
  • Ginko Biloba  (Ginko biloba)  (PE8)
  • Celery Seed  (Apium graveolens L.)  (PE12)
  • White Willow  (Salix alba)  (PE21)

 

The six identified PEs out of the thirty-seven PEs that were examined showed the highest percentage increase of lifespan, (also known as the chronological lifespan (CLS)), in the yeast,   The researchers determined both the mean (average) CLS and the maximum CLS of the six PEs.

Table 2 below list the six PEs and their mean and max. CLS:

Table 2: Percent increase of lifespan of S. cerevisiae by 6 PEs

Plant Extract (PE)Mean CLSMax CLS
PE4 (Black Cohosh)195%100%
PE5 (Valerian)185%87%
PE6 (Passion Flower)180%80%
PE8 (Ginko Biloba)145%104%
PE12 (Celery Seed)160%107%
PE21 (White Willow)475%369%
CLS - Chronological Lifespan

(Source:  Discovery of plant extracts that greatly delay yeast chronological aging and have different effects on longevity-defining cellular processes)

The researchers noted that PE21 appears to be the most potent longevity-extending pharmacological intervention presently known. It increases the mean and maximum CLS of yeast by 475% and 369%, respectively.  PE21 or White Willow bark represents a much greater effect than rapamycin and metformin, the two best drugs known for their anti-aging effects.

These findings by the researchers imply that these extracts slow aging in the following ways:  3

  • PE4 (Black Cohosh) decreases the efficiency with which the pro-aging TORC1 pathway inhibits the anti-aging SNF1 pathway;
  • PE5 (Valerian) mitigates two different branches of the pro-aging PKA pathway;
  • PE6 (Passion Flower) coordinates processes that are not assimilated into the network of presently known signaling pathways/protein kinases;
  • PE8 (Ginko biloba) diminishes the inhibitory action of PKA on SNF1;
  • PE12 (Celery Seed) intensifies the anti-aging protein kinase Rim15; and
  • PE21 (White Willow) inhibits a form of the pro-aging protein kinase Sch9 that is activated by the pro-aging PKH1/2 pathway.

The researchers showed that each of these six PEs decelerates yeast chronological aging and has different effects on several longevity-defining cellular processes, as illustrated in Figure 1.

An external file that holds a picture, illustration, etc. Object name is oncotarget-07-50845-g009.jpg

Figure 1.  A model for how PE4, PE5, PE6, PE8, PE12 and PE21 delay yeast chronological aging via the longevity-defining network of signaling pathways/protein kinases.  Activation arrows and inhibition bars denote pro-aging processes (displayed in blue color) or anti-aging processes (displayed in red color). Pro-aging or anti-aging signaling pathways and protein kinases are displayed in blue or red color, respectively.  (Source: Discovery of plant extracts that greatly delay yeast chronological aging and have different effects on longevity-defining cellular processes)

Each of the six PEs have different effects on cellular processes that define longevity in organisms across phyla. These effects include the following:

  • increased mitochondrial respiration and membrane potential;
  • augmented or reduced concentrations of reactive oxygen species;
  • decreased oxidative damage to cellular proteins, membrane lipids, and mitochondrial and nuclear genomes;
  • enhanced cell resistance to oxidative and thermal stresses; and
  • accelerated degradation of neutral lipids deposited in lipid droplets.

The researchers also revealed that certain combinations of the six PEs could markedly increase aging-delaying proficiencies of each other.

In conclusion, the study stated that the obvious challenge was to assess whether any of the six PEs can delay the onset and progression of chronic diseases associated with human aging.  Idunn Technologies is collaborating with four other universities for six research programs, to go beyond yeast, and work with an animal model of aging, as well as two cancer models.  4

This study and ongoing research reveals five features of the six PEs as potential interventions for decelerating chronic diseases of old age. These five features include:  5

  • the six PEs are caloric restriction (CR) mimetics that imitate the aging-delaying effects of the CR diet in yeast under non-CR conditions;
  • they are geroprotectors that slow yeast aging by eliciting a hormetic stress response;
  • they extend yeast longevity more efficiently than any lifespan-prolonging chemical compound yet described;
  • they delay aging through signaling pathways and protein kinases implicated in such age-related pathologies as type 2 diabetes, neurodegenerative diseases, cardiac hypertrophy, cardiovascular disease, sarcopenia and cancers; and
  • they extend longevity and delay the onset of age-related diseases in other eukaryotic model organisms.

High-mobility group protein 1 (HMG-1): A Marker of Chronic Inflammation

High-mobility group protein 1 (HMG-1) is a protein that in humans is encoded by the HMGB1 gene.

HMGB1 turns on the release of chemical signals called cytokines that generate inflammation in your body.

The molecule HMGB1 is responsible for initiating acute inflammation, which is a helpful reaction when your body is under attack by germs, or following an injury. Unfortunately, when a cell is damaged, its contents of HMGB1 leak out, leading to chronic inflammation.

When HMGB1 leaks out, it acts as a “danger signal” that triggers the release of chemical signaling molecules (called cytokines) that call in more white blood cells, which release still more cytokines, in a vicious cycle.

Inhibiting HMGB1 is a powerful means of slowing and reversing the processes involved in inflammation.

HMGB1 serves as a risk factor for memory impairment, chronic neuro-degeneration, and progression of neuro-inflammation. 1

The Table below lists the recognized and researched substances that may inhibit High-mobility group protein 1 (HMG-1):

Substances that Inhibit HMGB1

HMGB1  
CategoryNutraceuticals/Foods/HerbsReference(s)
Foods
Mung Bean Coat Extract1 2 vitexin, isovitexin
Herbs
Green Tea4 5 6 7
Angelica sinensis (Dong Quai)8
Lipids
Glycyrrhizin (Licorce)9


Resources:

Life Extension Cytokine Suppress with EGCG


 

Astaxanthin and Other Natural Substances Increase the Activity of the FOXO3 Longevity Gene

The gene FOXO3a codes for a human protein called Forkhead box O3, also known as FOXO3.

FOXO3 belongs to the family of transcription factors which are characterized by a distinct fork head DNA-binding domain. There are three other FoxO family members in humans:

  • FOXO1
  • FOXO4
  • FOXO6

Protein FOXO3 PDB 2K86.png

Structure of protein FOXO3. Based on PyMOL rendering of PDB 2K86  (Source: Pleiotrope – Own work, Public Domain, https://commons.wikimedia.org/w/index.php?curid=15989699)

This important protein has many vital functions in the human body and is primarily associated with human longevity, which is why it is often referred to as the “longevity gene”.  1  2 

Among the many functions and roles that this protein plays in the human body, the most important have been identified:

  • functions as a trigger for apoptosis through upregulation of genes necessary for cell death  3
  • upregulates antioxidants such as catalase and MnSOD  4
  • suppresses tumorgenesis in cancer  5
  • functions in DNA repair mechanisms  6  7
  • promotes resistance to oxidative stress  8

These important functions of the FOXO3 protein will only happen when the FOXO3 gene is activated and increased to encode the protein. 

Researchers have identified certain natural substances that activate and increase the FOXO3 gene:  These natural substances include:

  • Astaxanthin 9
  • Baicalein (from the Scutellaria baicalensis root or Baikal skullcap)  10
  • Butyrate (as Calcium Magnesium Butyrate) 11
  • R-Lipoic Acid 12
  • Selenium 13
  • Vitamin D  14

A Closer Look at Astaxanthin

Astaxanthin is a keto-carotenoid which belongs to a larger class of chemical compounds known as terpenes.  Astaxanthin is usually classified as a xanthophyll.

Astaxanthin can be found in:

  • microalgae
  • yeast
  • salmon
  • trout
  • krill
  • shrimp
  • crayfish
  • crustaceans
  • feathers of some birds (e.g., flamingos)

A recent study published in 2017 and co-authored by the The University of Hawaii John A. Burns School of Medicine (“JABSOM”) and Cardax, Inc. (“Cardax”), a Honolulu based life sciences company, demonstrated that the Astaxanthin compound (CDX-085 (developed by Cardax)) is able to switch on the FOX03 ‘longevity gene’ in mice.  15

Researchers of the study stated that all humans have the FOXO3 gene, which protects against aging in humans, but about one in three persons carry a version of the FOXO3 gene that is associated with longevity. By activating the FOXO3 gene common in all humans, researchers stated that they can make it act like the “longevity” version. This important study has shown that Astaxanthin “activates” the FOXO3 gene.

The study used mice which were fed either normal food or food containing a low or high dose of the Astaxanthin compound CDX-085 provided by Cardax. They witnessed a significant increase in the activation of the FOXO3 gene in the heart tissue of those mice that were fed the higher amount of the Astaxanthin compound.  In fact, they found a nearly 90% increase in the activation of the FOXO3 gene in the mice fed the higher dose of the Astaxanthin compound CDX-085. 

The researchers concluded that their hope is that these findings will lead to a highly effective anti-aging therapy that extends the lifespan of human beings.