from the patent
https://patents.google.com/patent/US9474776
where even Randy is mention ...
Honey contains several substances that activate nutrient sensing,
metabolic, detoxification and immune processes in the European honey bee *Apis
mellifera*, plus other chemicals useful to honey bee health. The enzymes
are found on the pollen walls of flowers and enter the honey by sticking to
the bees' legs. Ingestion of tree resins, balsams and tree saps via
incorporation into propolis or bee glue is also known to reduce bee
susceptibility to both insecticides and microbial pathogens and up-regulate
the transcription of the detoxification genes. Honey substitutes or pollen
patties, which don't contain these chemicals, may therefore contribute to
colony collapse disorder. See Mao, Wenfru, Schuler, Mary A. and Berenbaum,
May R., Honey constituents up-regulate detoxification and immunity genes in
the western honey bee *Apis mellifera, Proceedings of the National Academy
of Sciences of the United States, *110(22), 8842-8846 (2013). Mao et al.
found that constituents in honey derived from pollen and tree exudates,
including p-coumaric acid (=4-hydroxycinnamic acid), pinocembrin,
pinobanksin and pinobanksin 5-methyl ether, are strong inducers of
cytochrome P450 genes detoxification genes via a number of CYP6 and CYP9
family members. Massively parallel RNA sequencing and RNA-seq analysis
revealed that p-coumaric acid specifically up-regulates all classes of
detoxification genes as well as select genes for antimicrobial peptides
required for defense against pesticides and pathogens.
Those species of honey bees that nest in tree cavities use propolis to seal
cracks in the hive, as do bees in domestic hives, although feral honey bees
coat the entire inner surface of their nesting cavity, whereas domesticated
honey bees lay down comparatively little resin in beekeeping hives. The
coating of propolis has been demonstrated to inhibit AFB (Antúnez 2008),
fungi, and wax moth; Spivak has demonstrated that propolis from some
regions is effective against *Varroa*, and is investigating its effect on
viruses. Of great interest is the finding (Simone 2009) that the abundance
of propolis appears to decrease the necessary investment in immune function
of bees—thus, the bee colony, by self-medicating with antimicrobial
chemicals from plants, incurs less of a metabolic cost in fighting
pathogens. Oliver, Sick Bees—Part 3: The Bee Immune System, American Bee
Journal, October 2010.
...
The inventor now hypothesizes that the *Fomitopsis *colonization of the
wood from bear foraging and the entry wound site (see above) would lead to
the production of enzymes (laccases, lignin peroxidases, cellulases),
ergosterols and other sterols, mycoflavonoids and especially arrays of
nutritious complex polysaccharides that would not only soften the wood,
provide water, nutrition, and emit fragrances, all of which would attract
bees, while the extracellular exudates being secreted by the mycelium would
be rich in p-coumaric acids and coumarins and the glycosides of
unsubstituted and substituted benzoic, cinnamic and coumaric acids, all
stimulating the up-regulation of innate cytochrome p450 genes and enzymes
and also providing antiviral and antibacterial agents, all expressed during
the decomposition of the infected tree. A complex fungal tree nectar is
exuded, one that provides physiological benefits and boosts the innate
immunity of bees via numerous pathways as the trees decompose. In some
instances, bees nest within these logs or in the ground beneath them,
benefitting from long-term contact. The bees can then incorporate these
beneficial agents into their honey, propolis and combs so to as to protect
the brood, the queen and ultimately the colony.
....
Extracts of *Fomitopsis pinicola, Fomes fomentarius, Inonotus obliquus
Ganoderma resinaceum *(*Ganoderma lucidum *var. *resinaceum*) and
*Schizophyllum
commune *have now been found to be effective in reducing the viral burden
of honey bees and extending the life or worker bees. “As an entomologist
with 39 years of experience studying bees, I am unaware of any reports of
materials that extend the life of worker bees more than this.”—Dr. Walter
“Steve Sheppard, Chair, Department of Entomology, Washington State
University, Pullman, Wash. (personal communication). The inventor now
anticipates, as a consequence of this invention, that other woodland
polypore mushrooms, for instance the birch polypore, *Piptoporus betulinus*,
and numerous other woodland species will have greater and lesser antiviral
and longevity enhancing effects on bee health when the extracts of the pure
cultured mycelium are grown and diluted to within an optimal range, and
presented as food, in the feed water, into honey, pollen patties, propolis,
or even incorporated into the wood frames used to construct bee hives or
incorporated into sticky strips applied to bee hives. The predominant viral
species of concern are Deformed Wing Virus, Sacbrood virus, Israeli Acute
Paralysis Virus and the Black Queen Cell Virus, each one of which may
exacerbate the activity of other viruses, and pathogens, as immunity fails
from the deleterious cumulative effect from these and other multiple
stressors.
...
In essence, the inventor has devised a novel nutraceutical which is rich is
a wide array of coumarins, phenols and polyphenols; and anti-viral,
anti-fungal, anti-bacterial and anti-protozoal agents, and a wide diversity
of specialized metabolites such as antioxidants and antimutagens, which are
generated as a result of mycelium digesting grains or wood and are
attractive to bees and supportive of their host defense against stressors
and diseases. The extracts of mushrooms used medicinally for human health
have an unexpected benefit for bee health, including lowering antiviral
counts and extending bee lifespans. Indeed, the fungal contribution to
propolis and honey, as well as to pollen, augments the immune systems of
bees, and by extension to people, on specific, fundamental, complex levels.
The inventor notes extracts of mycelium grown on grain inoculated wood are
expected to contain more polyphenols, coumarins and compounds that
up-regulate detoxification and immunity genes in the bees, as opposed to
extracts of mycelium grown via liquid fermentation.
...
As bees are limited in the number and variety of enzymes needed to denature
natural and anthropogenic toxins, these toxins impair their baseline
immunity, making them more susceptible to pathogens from numerous
vectors—from *Varroa *mites, *Nosema *and microsporidia fungi, Phorid
flies, and the viruses and bacteria they carry. By increasing the bees'
ability to degrade these toxins by up-regulation of more cytochrome P450
genes, GST genes and/or CCE genes, the bees' immune state is improved to
better resist these assaults and other stress factors. Moreover, by
providing bees with a blend of fungal extracts that specifically limit the
severity of assaults from Phorid flies, *Varroa *mites, *Nosema *fungi and
viruses, bee colony health can be fortified for the long-term health of the
brood, the workers, the queen and her drones. These fungal components are
naturally incorporated into the honey and propolis, thus imparting an
advantage to developing generations. Ultimately, not only are bees are
protected, but honey production is expected to increase, and the quality of
the honey better supports downstream generational health and survivability.
...
P-coumaric acid, found in both grains and lignin, is a monomer of
sporopollenin, the principal constituent of pollen cell walls and propolis,
the resinous compounds gathered and processed by bees to line wax cells.
P-coumaric acid is essential for increasing laccase in wood rotting fungi,
a cellulase enzyme that breaks down lignin in wood, creating derivative
compounds palatable to insects as food, as well as creating habitats (bees
can take up residence in tunnels bored by mycophagous beetles). As fungi
rot wood, breaking down lignin, they also weep water, rich in these
p-coumaric and nutraceutical compounds beneficial to bees. The more
p-coumaric acid, the more laccases expressed by the mycelium, the more the
wood rots, the more fungal polysaccharides (sugars) and ultimately the more
these compounds will be in the fungal exudates that the bees seek and from
which they benefit. That wood rotting fungi produce p-coumaric acids and
coumarins that can be bio-converted into p-coumaric acids is yet another
advantage of this invention.
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