Monthly Archives: May 2017


Are You Methylating Properly?

The methylation pathways in the body is critical to good health. There are various functions of methylation within the body:

  • detoxification of carcinogens and other toxins
  • repair damage DNA
  • the formation of new cells
  • the manufacture of certain hormones

One of the indicators that the body is not methylating properly is a high homocysteine serum level.

Methylation is the transfer of a methyl group, which is what happened with carbon attached to three atoms of hydrogen, from one molecule to another.

Methylation is composed of two components:

1. Methyl donors-methyl donors are compounds that supply the methyl groups needed for methylation.

2. Methylating factors-methylating factors are nutrients that assist with the methylation process by providing enzymes that detach the methyl groups from the methyl donors and reattach them to other molecules.

Methyl donors consists of the following:

  • Methionine
  • Choline
  • Trimethylglycine (TMG)
  • Dimethylglycine (DMG)
  • S-Adenosyl methionine (SAMe)

Methylating factors consist of the following:

  • Vitamin B12
    • Three active forms:
      • Methylcobalamin
      • Hydroxocobalamin
      • Adenosylcobalamin
      • Never consume Cynocobalamin
  • Vitamin B6  (as P-5-P (Pyridoxal 5-Phosphate))
  • Folate
    • Two active forms:
      • L-5-MTHF as (6S)-5-methyltetrahydrofolate
      • L-5-FTHF  (5-formyltetrahydrofolate) as folinic acid calcium salt) (folinic acid)
  • Zinc

When the body is deficient in both methyl donors or methylating factors detoxification and repair functions of the body are compromised.

Methylation is the enzymatically-catalyzed process of adding a methyl group to proteins, DNA and RNA. This process is involved in RNA metabolism and the regulation of gene expression and protein function. While it does not change the sequence of the genome, methylation determines which genes are expressed and are responsible for changes in gene expression.

In general, methylation is a normal process that occurs in humans. DNA methylation has been found to play an important role in embryonic development, genomic imprinting, X-chromosome inactivation in females and cases where individuals possess two X-chromosomes, and chromosome stability.

Studies have found that embryos lacking the enzyme that catalyzes the transfer of a methyl group to DNA die during the differentiation stage. The methylation of histones, proteins involved in the packaging and ordering of DNA into structural units, regulates processes such as gene transcription and DNA repair.

Given the importance of methylation, errors in the process can result in devastating genetic disorders and human diseases. For instance, a loss of methylation results in the genomic instability present in the tumor cells of an individual with cancer.

On the other hand, if methylation is present in cells that are normally unmethylated and cause the process of transcribing DNA into RNA to be silenced, tumors can develop that in turn can lead to cancer (i.e., colon cancer).

Aside from cancer, errors in DNA methylation are also responsible for:

  • Immunodeficiency-centromeric instability-facial anomalies syndrome (ICF syndrome)
  • Prader-Willi syndrome
  • Angelman’s syndrome
  • Beckwith-Wiedemann syndrome 


You can ask your doctor to test your Methylation Pathway in order to determine the effectiveness of the functions and levels of its various biochemical pathways and to determine if there are any single nucleotide polymorphisms (SNPSs) in the Methylation Pathway.

Two labs that can test the Methylation Pathway:

Doctor’s Data, Inc.

Methylation Profile; plasma

    Sample Report of Methylation Profile; plasma

DNA Methylation Blood Spot

Identification of SNPs that influence health and disease risk may improve clinical success and allow patients to optimize health and wellness.

    Sample Report of DNA Methylation Blood Spot

Health Diagnostics and Research Institute

The Methylation Pathway

Cover photo credit: Dr. Amy Yasko

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

Freezing Broccoli Sprouts Increases Sulforaphane Yield

Three-day old broccoli sprouts are concentrated sources of glucoraphanin, which is the precursor to sulforaphane.  Fresh broccoli sprouts contain 10 to 100 times more glucoraphanin by weight than mature broccoli plants. 1  Fresh broccoli sprouts can contain at least 73 mg of glucoraphanin (also called sulforaphane glucosinolate) per 1-oz serving.

A study from 2015 published in the journal RSC Advances by researchers from the College of Food Science and Technology, Nanjing Agricultural University, Nanjing, People’s Republic of China and the College of Food Science and Engineering, Qingdao Agricultural University, Qingdao, People’s Republic of China, investigated whether freezing broccoli sprouts would have an effect on glucoraphanin and ascorbic acid content, myrosinase activity, sulforaphane and sulforaphane nitrile formation.  2

The researchers froze broccoli sprouts at −20 °C (DF-20), −40 °C (DF-40) and −80 °C (DF-80) or stored at −20 °C (LN-20), −40 °C (LN-40) and −80 °C (LN-80) after being frozen in liquid nitrogen for 5 min or always frozen in liquid nitrogen (LN).

The results showed the following:

  • glucoraphanin content was not significantly affected by freezing
  • myrosinase activity was enhanced
  • sulforaphane yield  was increased by 1.54–2.11 fold
  • sulforaphane nitrile formation decreased
  • ascorbic acid content was decreased

By freezing fresh broccoli sprouts, sulforaphane can be increased by on average 1.825 times its original value when fresh and not frozen. 

Eating frozen broccoli sprouts may not be very appetizing.  Instead it is recommended to use the frozen broccoli sprouts in a smoothie.  Make sure you use the broccoli sprouts straight from the freezer and do not allow them to thaw.  

Inhibiting the Fibrillogenesis of Alpha-synuclein and Amyloid-beta by Natural Substances


A group of neurodegenerative disorders characterized by fibrillary aggregates of alpha-synuclein protein in the cytoplasm of selective populations of neurons and glia is called Synucleinopathies or alpha-Synucleinopathies. 

Synucleinopathies include:

  • Parkinson’s disease (PD)
  • Dementia with Lewy bodies (DLB)
  • Pure autonomic failure (PAF)
  • Multiple system atrophy (MSA)

These neurological disorders are characterized by a chronic and progressive decline in the following bodily functions:

  • autonomic
  • behavioral
  • cognitive
  • motor skills

Alpha-synuclein protein

Synucleinopathies are caused by the abnormal accumulation of aggregates of alpha-synuclein protein in:

  • glial cells
  • nerve fibers
  • neurons

Alpha-synuclein is a protein that is abundant in the human brain and is predominantly expressed in the:

  • cerebellum
  • hippocampus
  • neocortex
  • substantia nigra
  • thalamus

It is also found in smaller amounts in the heart, muscles, and other tissues. 

Figure 1.  This a rendering of the Alpha-synuclein protein, based the PDB file of 1XQ8 using Rasmol.  (Source:  Hantanplan)

In the brain, alpha-synuclein is found primarily at the end of the neurons in specialized structures called the presynaptic terminal. The presynaptic terminal is a specialized area within the axon of the presynaptic cell that contains neurotransmitters enclosed in small membrane-bound spheres called synaptic vesicles.  The release of neurotransmitters from the presynaptic terminal relays signals between neurons.  Dysfunctional presynaptic terminals due to aggregation of alpha-synuclein can compromise normal brain function.

Lewy bodies

When alpha-synuclein aggregates, it forms insoluble fibrils in pathological conditions characterized by Lewy bodies.  Alpha-synuclein is the primary structural component of Lewy body fibrils, even though Lewy bodies may also contain:

  • alpha B crystallin
  • neurofilament protein
  • tau protein
  • ubiquitin

Lewy neurites are abnormal neurites in diseased neurons, containing granular material and abnormal alpha-synuclein filaments similar to those found in Lewy bodies.

Figure 2.  Microscope photograph of a Lewy body  (Source:  By Dr. Andreas Becker upload here Penarc – Own work, CC BY-SA 3.0)

Inhibiting the Fibrillogenesis of alpha-synuclein and amyloid-beta by Natural Substances

Researchers have focused on finding ways to inhibit the fibrillogenesis of alpha-synuclein in order to halt the formation of pathological conditions characterized by Lewy bodies.

Beginning in 2008, then in 2010 and 2011, researchers have been able to identify two natural substances that not only inhibits the fibrillogenesis of alpha-synuclein, but also at the same time inhibits amyloid-beta fibrillogenesis, the major cause of vascular dementia and Alzheimer’s disease.

These two natural substances include:

  • (-)-epigallocatechin gallate  (EGCG)  
  • theaflavins  

(-)-epigallocatechin gallate (EGCG) is found in high content in the dried leaves of white tea (4245 mg per 100 g), green tea (7380 mg per 100 g) and, in smaller quantities, black tea.  Smaller trace amounts can be found in apple skin, plums, onions, hazelnuts, and pecans.

Theaflavins are formed from the condensation of flavan-3-ols in tea leaves during the enzymatic oxidation of black tea.

In 2008, researchers demonstrated the redirection of amyloid fibril formation through the action of a small molecule, resulting in off-pathway, highly stable oligomers.

The polyphenol (-)-epigallocatechin gallate efficiently inhibits the fibrillogenesis of both alpha-synuclein and amyloid-beta by directly binding to the natively unfolded polypeptides and preventing their conversion into toxic, on-pathway aggregation intermediates. Instead of beta-sheet-rich amyloid, the formation of unstructured, nontoxic alpha-synuclein and amyloid-beta oligomers of a new type is promoted, suggesting a generic effect on aggregation pathways in neurodegenerative diseases.  1

Researchers in 2010 reconfirmed the fact that the polyphenol (-)-epi-gallocatechine gallate (EGCG) inhibits alpha-synuclein and amyloid-beta fibrillogenesis.  2  They showed that EGCG has the ability to convert large, mature alpha-synuclein and amyloid-beta fibrils into smaller, amorphous protein aggregates that are nontoxic to mammalian cells.

Finally, in 2011, researchers showed that theaflavins (TF1, TF2a, TF2b, and TF3), the main polyphenolic components found in fermented black tea, are potent inhibitors of amyloid-beta and alpha-synuclein fibrillogenesis.  3  Theaflavins stimulate the assembly of amyloid-beta and alpha-synuclein into nontoxic, spherical aggregates that are incompetent in seeding amyloid formation and remodel amyloid-beta fibrils into nontoxic aggregates.

Their conclusion suggested that theaflavins might be used to remove toxic amyloid deposits.

These three studies confirm the fact that adding green tea, white tea and/or black tea to your diet in order to obtain both EGCG and theaflavins may be a promising therapy to prevent Synucleinopathies, Dementia and Alzheimer’s disease.   

Cover photo credit: SUNY Oneonta

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.