Bill Faloon on what's delaying regenerative medicine in 2023.pptx

Marriott Hotel
West Palm Beach, Florida
William Faloon
February 9th 2023
What’s Delaying
Regenerative Medicine?

Unparalleled Track Record
of Biomedical Innovation
First Established 1977

World’s Largest Longevity Organization
https://www.lifeextension.com/about/life-extension-story/history

age-reversal.net
This presentation and info
about aging research available at:

“FDA is responsible for advancing the public health by
helping to speed innovations that make medical
products more effective, safer, and more affordable…”1
1. https://www.fda.gov/about-fda/what-we-do
FDA Headquarters, Rockville, Maryland

What FDA says:
“FDA is responsible for
advancing the public
health by helping to speed
innovations that make
medical products more
effective, safer, and more
affordable…”1
“FDA is responsible for
impairing the public
health by delaying
innovations that make
medical products less
effective, less safe, and less
affordable…”2
What FDA does:
= Needless Deaths
2. FDA Holocaust Museum- 1994-2022

"We stand on the cusp of a revolution in
health care. Advances in molecular medicine
will allow us to develop powerful new
treatments that can cure or even prevent
diseases like Alzheimer's and cancer."1
"What's missing," according to Dr. von Eschenbach:
1.https://www.lifeextension.com/magazine/2012/12/former-fda-commissioner-admits-risk
Former FDA commissioner
Andrew von Eschenbach, M.D.:

FDA Commissioner Margaret
Hamburg’s sworn testimony:
1.https://www.lifeextension.com/magazine/2012/12/former-fda-commissioner-admits-risk
Margaret Hamburg M.D.

https://www.cato.org/commentary/rethinking-fda
“If the FDA delays a good drug, the cost is less obvious
because most of those affected are not aware their illness
could have been treated more effectively. A great deal
of evidence supports this perspective and estimates huge
life‐saving benefits would be derived from greater speed.”
August 24th, 2022
“Scientists have shown aging process
can be safely and effectively
“Rethinking the FDA”

January 6, 2023
“The reversal of aging could hinge on one huge decision.”
“If the FDA classifies aging as a disease,
drug companies can take a new
approach to curing death.”
https://www.popularmechanics.com/science/health/a42419017/anti-aging-drugs-fda-approval/
“Humans Can Start Living Longer
—Once the FDA Does This”
“Scientists are already targeting proteins
in cells to keep them from degenerating.”
“TheWHOsupportsthegrowingtrendofcallingagingadisease.”

| Jan. 11, 2023
“FDA Increasingly Halting Human Trials…”
Clinical holds by FDA can stifle progress:
2017-2020: 557 clinical holds*
2002-2021: 664 clinical holds
2021-2022: 747 clinical holds
“FDA is also saying that's probably part of the reason it's having to
press pause on more trials because the technology is just so new.”
*average each year

Our Controversial Contention
It may be possible…
To Reverse Aging in Humans Today
www.age-reversal.net

Feb 23 /March 2, 2015
TIME describes
the prospect of
delayed aging.
Early Media
Report Year 2015

https://www.pressreader.com/usa/popular-science/20180505/281672550562011
“Bill Faloon has pursued immortality for
decades. Now he’s got lots of company.
What does science have to say?”
“The FOREVER Man” May 5, 2018

https://www.newscientist.com/article/mg23931920-600-how-a-positive-mind-really-can-create-a-healthier-body/
“He stirred controversy with his plans to bring back the woolly mammoth. But first
he’s working on editing sperm – and trying out his aging reversal techniques on dogs.”
“George Church: The maverick
geneticist now wants to reverse aging”
August 25th, 2018

April 27, 2019
https://www.newscientist.com/issue/3227/

According to Juvenescence’s Greg Bailey
“We won’t be aging as fast or
poorly as our parents”
“I think the world is going to be shocked”
Juvenescence has now raised $165 million
to fund longevity projects with the goal of
extending human lifespans to 150 years.
“Science fiction has become science”
‘Extraordinary’ Breakthroughs In Anti-Aging
Research ‘Will Happen Faster Than People Think’
https://www.forbes.com/sites/robinseatonjefferson/2019/08/26/how-extraordinary-breakthroughs-in-anti-aging-research-will-happen-faster-than-people-think

https://www.technologyreview.com/magazine/2019/09 September
2019
“Later this year, at a conference
of longevity enthusiasts called
RAADfest, to be held in Las
Vegas, Faloon plans to take the
strategy one step further with
what he has been calling the
“Perpetual Clinical Trial.”
“OLD AGE IS OVER!”

“Reversal of epigenetic aging and immunosenescent trends in humans.” Aging Cell; Sept 2019
Human Age Reversal Demonstrated in 2019
1) Human growth hormone
2) DHEA
3) Metformin
Study conducted by Dr. Greg Fahy in collaboration
with researchers from Stanford University and
UCLA used individualized doses of:
Study subjects also provided with daily
vitamin D3 and zinc.

https:// www.dailymail.co.uk/health/article-7435427/
Oct.22,2019
Turning Back Time!
“Aging is REVERSED in men using a
cocktail of growth hormones and
diabetes drugs in study that saw test
group shed 2.5 biological years.”

 Once-faltering paws gripped objects
with renewed strength.
 Hearts and livers of rats regained
youthful vitality.
 Fuzzy memories sharpened.
 Biological age had been cut in half.
“It was as if someone had turned back time.”
April 30, 2022
“GrowingYounger:RadicalInsights IntoAgingCouldHelpUsReverse It”
April 30,2022|https://www.newscientist.com/issue/3384/

June 7
2022
https://www.technologyreview.com/2022/06/07/1053132/saudi-arabia-slow-aging-metformin/
The oil kingdom fears that its population is aging at an accelerated rate and hopes
to test drugs to reverse the problem. First up might be the diabetes drug metformin.
Saudi Arabia Plans To Spend $1 Billion A
Year Discovering Treatments To Slow Aging
of its oil wealth supportingbasic research on the biology of aging and
findingwaysto extend the number of years people live in good health
$1 BILLION A YEAR
has started a not-for-profit organization
called the Hevolution Foundation that plans to spend up to
“
”

 The field of geroscience aims to find ways to delay onset of age-related diseases.
 Geroscience experts met virtually at a symposium of the New York Academy of Sciences.
 Advances made in understanding the mechanisms underlying biological aging.
“The presentations focused on identifying biomarkers
of aging and the search for interventions to prevent and
treat age-related diseases.”
https://www.medscape.com/viewarticle/985809
“FDA does not recognize aging as an indication for drug approval…”
December19th,2022

https://www.nationalgeographic.com/magazine/article/aging-cure-longevity-science-technology-feature/
Dec. 28, 2022

“A Drug to Treat Aging May Not Be a Pipe Dream”
“By the end of 2023, it’s likely that one of these
ideas will be shown to work in humans.” www.wired.com/story/drugs-aging-medicine-biotech/
►“In 2023, early success of these treatments
could kickstart the greatest revolution in
medicine since the discovery of antibiotics.”
►“Senolytics aren’t the only contenders…but
the success of a drug targeting an aspect of
aging in clinical trials will allow us to consider
this loftier goal in the not-too-distant future.”
Jan. 1st, 2023
New approaches to the biology of senescence can make lives longer and healthier.

The start-ups seeking a cure for old age
 Eric Verdin, chief executive of the Buck Institute, “scientists
have completely changed how they think about ageing”
“Tech billionaires are funding research
to help us live longer and healthier lives”
“Thestart-ups seeking acureforoldage”
January 2, 2023 https://www.ft.com/content/649b0446-698c-4363-82ad-0be5b5faa68f
 Nir Barzilai, Institute for Aging Research at Albert Einstein College of Medicine “the world
is on the cusp…of finding transformational drugs that prevent the effects of ageing…”
 Mehmood Khan, chief executive of Hevolution Foundation (Saudi Arabia),
“its vision is to “extend healthy lifespan for the benefit of all humanity”

March 7, 2022
Scientists
Reverse Aging in Mice

March 11, 2022
“Anti-Aging Breakthrough:
https://scitechdaily.com/anti-aging-breakthrough-cellular-rejuvenation-therapy-safely-reverses-the-aging-process-in-mice/
Cellular rejuvenation therapy safely reverses signs of
aging in mice. Credit: Salk Institute
Cellular Rejuvenation
Therapy Safely Reverses
the Aging Process in Mice”

March 9, 2022
“Newresearchbythe
SalkInstitutehasshown
cellularrejuvenation
therapysafelyreverses
signsofaginginmice.”
https://www.drugtargetreview.com/news/101826/scientists-have-shown-ageing-process-can-be-safely-and-effectively-reversed-in-mice/
“Scientists have shown aging process can
be safely and effectively reversed in mice”

https://www.dailymail.co.uk/sciencetech/article-10589031/Scientists-REVERSE-ageing-mice-using-cellular-rejuvenation-technique.html
• Experts injected mice with molecules called the Yamanaka transcription factors
• Treatment period of seven to 10 months was effective for restoring youthfulness
• The 'safe' treatment could one day help humans wind back their biological clock

March 7, 2022
https://www.salk.edu/news-release/cellular-rejuvenation-therapy-safely-reverses-signs-of-aging-in-mice/
Mar. 7, 2022
“Scientistssafelyandeffectivelyreversetheagingprocessinmiddle-aged
andelderlymicebypartiallyresettingtheircellstomoreyouthfulstates.”

• Partial cell reprogramming in live (in vivo) mice
• OSKM (“Yamanaka”) transcription factors used
• Longeradministrationdemonstrateduniquebenefits
• No toxicity or increase in cancer detected
Partial Cell Reprogramming Safe
https://www.nature.com/articles/s43587-022-00183-2

Transcription factors can enable old cells to be
reprogrammed into embryonic cells capable of
developing into all tissues of the body.
Transcription factors are proteins that help turn
specific genes "on" or "off" by binding to DNA.
Groups of transcription factors can turn
a gene on/off in specific parts of the body.
Transcription factors that are
repressors decrease transcription.
Transcription factors that are activators
boost a gene’s transcription.

The Nobel Prize in Physiology or Medicine 2012
These transcription factors are called:
“Yamanaka Factors”
Four specific genes encode transcription
factors that can convert somatic cells
into pluripotent stem cells that can
propagate indefinitely.
nobelprize.org/prizes/medicine/2012/yamanaka

https://hms.harvard.edu/news/loss-epigenetic-information-can-drive-aging-restoration-can-reverse
“Study in mice implicates changes to
way DNA is organized, regulated rather
than changes to genetic code itself”
“Loss of Epigenetic Information Can
Drive Aging, Restoration Can Reverse It”
Jan.12th,2023
1
“the extensive experiments led the team to conclude that “by manipulating
the epigenome, aging can be driven forwards and backwards”

Jan 12, 2023
https://www.cnn.com/2023/01/12/health/reversing-aging-scn-wellness/index.html
“Old Mice Grow Young Again…
Can People Do The Same?”
 Harvard researchers show aging may
be caused by changes in epigenetic
markers.
 Damaged DNA caused marked
acceleration in epigenetic age of mice.
 Researchers may have induced
aging by damaging DNA in mice.

“Scientists Have Reached a Key Milestone
in Learning How to Reverse Aging”
Jan. 12th, 2023
 Researchers then used
pluripotency factors “OSK” to
reversesomeofthisapparentaging.
 Age-related dysfunction might
be reversible by modifying
epigenetic status.
 Results suggest that aging might
be controlled by epigenetics.
https://time.com/6246864/reverse-aging-scientists-discover-milestone/

• Long-termcell reprogrammingresults in “younger”skin age.
• Skin cells divide more rapidly.
• Lower inflammation and reduced senescent-associated
secretory phenotypes in treated animals.
• No data collected on lifespan, exercise, memory, or muscle.
Cell Rejuvenation in Live Mice
https://www.nature.com/articles/s43587-022-00183-2

- January 9th, 2023
technologyreview.com/2023/01/09/1066488/biotech-says-mice-live-longer-after-genetic-reprogramming/
This Biotech Startup Says Mice Live
Longer After Genetic Reprogramming
“A small biotech company claims it has used a
technology called reprogramming to rejuvenate old
mice and extend their lives, a result suggesting that
one day older people could have their biological clocks
turned backwithaninjection—literally becomingyounger.”

Scientists at Rejuvenate Bio recently tested
epigenetic reprogramming in elderly mice
Jan. 5th, 2023
They gave 124-week-old mice gene
therapy with three Yamanaka factors: OSK
They reported that remaining lifespan
was more than doubled with treatment
Reference: https://www.biorxiv.org/content/10.1101/2023.01.04.522507v1 *Study has not yet been peer reviewed as of 1/24/2023.
Frailty was also reduced in treated mice

Jan. 5th, 2023
Yamanaka factors production capacity
induced in vivo in normal aged mice.
Expression of Yamanaka factors controlled
by oral doxycycline administration.
Human equivalent doubling of remaining
lifespan started in late life might enable:
Reference: https://www.biorxiv.org/content/10.1101/2023.01.04.522507v1
A 70-year-old with a life expectancy of
15 years to have it extended to 31 years.

Jan.5th,2023
Old mice injected with the Yamanaka factor encoded virus.
Adeno-associated virus encoded with three Yamanaka factors (OSK)
(Doxycycline used as Yamanaka factor promoter.)
Doxycycline in drinking water (one week on and one
week off) controllably promotes Yamanaka factors.
The start-ups seeking a cure for old age
RESULTS
► Reversal of epigenetic aging markers
► Restored youthful functions
► Extension of remaining lifespan by 109%
Reference: https://www.biorxiv.org/content/10.1101/2023.01.04.522507v1 *Study has not yet been peer reviewed as of 1/24/2023.

After large animal research, next step may be testing old people.
►Researchers can order Yamanaka factor-encoded
viral vectors from certified biologics suppliers.
What may be studied next….
►Inject into old dogs and old primates.
►Test differing doxycycline dosing schedules to turn
on Yamanaka factors and measure effects on aging.
Jan. 5th, 2023

> 2006: cell reprogramming demonstrates cellular rejuvenation.
> 2011: Rejuvenation induced in very old human cells (in vitro)
> 2022: 100% of Human Genome sequenced.
> 2022: Aging partially reversed in live mice (SALK)
> 2022: Research underway to rejuvenate old humans.
https://pubmed.ncbi.nlm.nih.gov/33627519
Cellular Reprogramming
--> Rewriting the Rules of Biology | https://pubmed.ncbi.nlm.nih.gov/33627519
> 2023: Aging partially reversed in live mice (Harvard + bioRxiv)

September 02, 2022 | https://doi.org/10.1111/acel.13696
September 2nd, 2022

“Umbilical cord plasma concentrate has beneficial effects on
DNA methylation GrimAge and human clinical biomarkers”
Human Study
• Each injection equivalent to 100 mL
umbilical cord plasma infusion.
September 02, 2022 | https://doi.org/10.1111/acel.13696
• 18 human participants average age 74 years.
• Safety-efficacy evaluated with blood tests +
GrimAge® epigenetic clock.
• Weekly injection of umbilical cord plasma
concentrate into muscle for 10 weeks.
(Fourumbilicalcordsusedtoproduceeachweeklyinjection.)

• GrimAge®: -0.78yearsyounger(predictorofdeathrisk)
• 30% of 90 biomarkers changed
beneficially, zero negatively
• No significant side effects
• Kidney function: 7% improvement
measured by eGFR (+ 5)
• Phenotypic Age Score biomarkers such as RDW
and MCV improved, reducing predicted age
September 2nd, 2022 https://onlinelibrary.wiley.com/doi/10.1111/acel.13696

Scientists have identified synergistic cellular pathways for
longevity that amplify lifespan fivefold in C. elegans, a
nematode worm used as a model in aging research.
“The increase in lifespan would be the
equivalent of a human living for 400 or 500
years, according to one of the scientists.”
Jianfeng Lan, Jarod A. Rollins, Xiao Zang, Di Wu, Lina Zou, Zi Wang, Chang Ye, Zixing Wu, Pankaj Kapahi, Aric N. Rogers, Di
Chen. Translational Regulation of Non-autonomous Mitochondrial Stress Response Promotes Longevity. Cell Reports, 2019;
28 (4): 1050 DOI: 10.1016/j.celrep.2019.06.078
“Pathways that extend lifespan
By 500 percent identified” Jan 8, 2020

https://www.webmd.com/healthy-aging/story/is-there-a-cure-for-aging
“Fueled in part by a billion
dollars of investor money, they
are attempting to reverse-
engineer your molecular
biological clock.
Their goal?
To eliminate not merely diseases
that kill people, but to prevent
death itself.”
Feb 20, 2021
Is There a Cure for Aging?

Dec. 30, 2020
https://fortune.com/2020/12/30/anti-aging-research-health-care-spending-biden/
Mainstream Recognition of
The Need to Reverse Human Aging
“Age is the biggest risk factor for cancer,
cardiovasculardisease,andneurodegeneration.
Withouttreatmentsto slowor reverseaspects
of biologicalaging,anagingpopulationmeans
we areinfor ahealthcarecosttsunami.
With such treatments, Americans would
experiencemorehealthy,productiveyearsoflife.”

“…why not launch an
Operation Warp Speed
for biological aging?”
CONCLUSION
https://fortune.com/2020/12/30/anti-aging-research-health-care-spending-biden/
December 30, 2020

Bridging the Longevity Gap
Urgent Need to Reform Clinical Trial Regulations

o 1497: Citrus shown to cure scurvy
o 1747: James Lind proves citrus cures scurvy
o 1870: Flawed study discredits “citrus cure”
o 1911: Dr. Robert Scott loses crew to scurvy
o 1932: Vitamin C proven to cure scurvy
Thousands of Deaths After Scurvy Cure Discovered

Delays
Caused Needless Deaths
From Bacterial Infections
•Antibiotic properties of penicillin discovered:1928
•Alexander Fleming’s findings published: 1929
•Penicillin not widely available until 1946
Millions of preventable deaths!
Alexander Fleming

Penicillin Availability
1928 1946
HumanAge Reversal
?
2015

Daily Deaths of Americans > age 64:
https://www.cdc.gov/nchs/fastats/older-american-health.htm
6,800 Human Lives Lost

The subcutaneous administering of 9 million international
units a day of the drug interleukin-2 to pancreatic cancer
patients three days before surgery induced the following
benefits compared to placebo patients administered saline:
Interleukin-2 versus Placebo
In Pancreatic CancerTreatment
Two-Year Survival
Three-Year Survival
Postoperative
Complications
Interleukin-2 Group Control (Saline) Group
33% 1o%
22% O%
33% 8O%

Survival of Prostate Cancer
Patients with Poor Prognosis:
Not Supplemented with melatonin:
5.34 Years
Supplemented with 3 mg of melatonin:
12.8 Years
Seven years increased survival in
melatonin-treated patients after
conventional treatment failure.

Dozens of companies selling Fisetin for years…
But does it have “senolytic” properties in humans?

 Professor James Kirkland at Mayo Clinic spearheading studies of fisetin.
 Dr. Kirkland describes clinical trial where FDA made him complete a 450 page-
detailed Investigational New Drug application.
 This had to be submitted to the FDA for approval to do a human study using fisetin.
 FDAthen mandates Kirkland doanimal and pharmacology studies before “allowing” aclinical trial.
 Fisetin has been ingested by people in various fruits and vegetables. It’s also been
used for years as a dietary supplement. It took 2.5 years for human study begin.
Example of FDA Delay of Clinical Trial on Fisetin
Bureaucratic barriers impede rapid testing
compounds that may slow/reverse aging processes.
Available at: https://www.youtube.com/watch?v=yqjuWdWtJF8. Accessed August 9, 2022.

Store Shelves Today are Packed with Dietary Supplements

 FDA seeks to classify most dietary
supplements as prescription drugs.
 Pharma spends huge amounts lobbying
Congress.
 One Senator stands in FDA’s way.
 Vitamin consumers inundate Congress
with protests.
Near certain victory for FDA fails
as Congress votes down anti-
supplement legislation.
August 15, 1974

 In early 1970’s FDA tried to re-classify many
food supplements into prescription drugs.
 Pharma heavily lobbied to gain exclusive
access to sell supplements.
 The Proxmire Amendment made it so
that food supplements could not be classified
as drugs, making their sale possible without a
prescription from a doctor.
 The Proxmire Amendment and others he
spearheaded became section 411 of
the Federal Food, Drug, and Cosmetic Act.
One Senator Saved Consumer Open Access to Dietary Supplements
1974-1976 Legislative Period
Senator William Proxmire
en.wikipedia.org/wiki/The_Proxmire_Amendment

GNC Indicted for Promotion of Primrose Oil
Nov. 15th, 1984
https://www.nytimes.com/1984/11/15/us/health-food-company-is-indicted-on-promotion-of-oil-of-primrose.html
Reason: FDA says no studies support safety/efficacy of primrose oil.
Investigation: Criminal investigation initiated in 1980.
FDA threat: GNC executives threatened with 5-year jail sentence.
Outcome: GNC corporation & two executives plead guilty.
GNC stops promoting primrose oil.

https://pubmed.ncbi.nlm.nih.gov/?term=oil%20of%20evening%20primrose
Dec .31st , 2022
HundredsofPublished Scientific StudiesSupportBenefits ofPrimroseOil

• Atopic dermatitis
• Inflammatory disorders
• Peripheral neuropathy
• Autoimmune conditions
• Renal function
• Rheumatoid arthritis
• Post menopausal symptoms
• Reduced cardiovascular risk factors
Potential Benefits of Evening Primrose Oil
References on following 36 slides of published scientific abstracts

Prostaglandins Leukot Med. 1982 Jun;8(6):641-5.
Protection against ethanol-induced embryonic damage
by administering gamma-linolenic and linoleic acids
P K Varma, T V Persaud
PMID: 6287501
Abstract
Many reports have now confirmed the teratogenic potential of alcohol in humans and in laboratory
animals. A characteristic pattern of congenital anomalies is present in infants born to mothers suffering
from chronic alcoholism. The pathogenesis of this condition is unclear. Chronic consumption of ethanol
causes a depletion of essential fatty acids, partly by blocking gamma-linolenic acid formation and partly by
depleting dihomogammalinolenic acid. Whether this action of ethanol on essential fatty acid and
prostaglandin metabolism may account for its teratogenic potential was investigated in the rat. Treatment
of pregnant rats with ethanol and evening primrose oil (efamol), a rich source of gammalinolenic acid, led
to a significant reduction in the embryopathic activity of ethanol.
https://pubmed.ncbi.nlm.nih.gov/6287501/

Rheumatol Int. 1984;4(4):165-7.
Primary Sjögren's syndrome treated with
Efamol/Efavit. A double-blind cross-over investigation
R Manthorpe, S Hagen Petersen, J U Prause
PMID: 6385206 DOI: 10.1007/BF00541208
Abstract
Thirty-six patients with primary Sjögren's syndrome participated in a randomised double-
blind, cross-over, 3-week, study to compare the effect of Efamol (1500 mg X 2) with that of
placebo. Efamol contains 9% of the prostaglandin-E1 precursor gamma-linolenic acid,
which is presumed to occur in reduced levels in Sjögren's syndrome. Efamol treatment
improved the Schirmer-I-test (P less than 0.03) while values of break-up time,-van
Bijsterveld score, corneasensitivity, tear-lysozyme and nuclear chromatin in conjunctival
epithelial cells did not reach the statistical 0.05 level.

Atopic dermatitis and essential fatty
acids: a biochemical basis for atopy?
S Wright
PMID: 3890448 DOI: 10.2340/00015555114143145
Abstract
The effects of dietary supplementation with evening primrose oil (Efamol) in 99 patients with atopic dermatitis
were investigated in a double blind, controlled crossover study. Simultaneously, plasma phospholipid essential
fatty acid status was determined in 50 of these patients before and after treatment. In a separate study,
lymphocyte subsets and mitogen responses were investigated in 15 atopic patients before and after treatment.
The conclusion is that evening primrose oil improves atopic dermatitis; an abnormality of the enzyme delta-6-
desaturase is proposed to explain the biochemical findings. Finally, it is concluded that the therapeutic effect of
evening primrose oil is unlikely to be mediated through a primarily immunological mechanism.
Atopic dermatitis and essential fatty acids:
a biochemical basis for atopy?
Clinical Trial Acta Derm Venereol Suppl (Stockh). 1985;114:143-5.

Beneficial effects of polyunsaturated fatty
acids in partially nephrectomized rats
Prostaglandins. 1986 Aug;32(2):211-9.
U O Barcelli, J Miyata, Y Ito, L Gallon, P Laskarzewski, M Weiss, R Hitzemann, V E Pollak
PMID: 3797690 DOI: 10.1016/0090-6980(86)90126-7
Abstract
Evening primrose oil, safflower oil, and salmon oil, all with high polyunsaturated fatty acid
content, were fed to partially nephrectomized rats; the effects were compared to those of
feeding beef tallow. All three oils had favorable effects on progression of renal failure, salmon
oil on kidney histology as well. The changes induced in platelet production of thromboxane A2,
and in the renal production of various eicosanoids may explain the protective role of these oils.

A Dib 1 , J P Carreau
PMID: 2821872 DOI: 10.1159/000177285
Abstract
The effects of dietary gamma-linolenic acid supplementation in the form of evening
primrose oil were examined in pregnant zinc-deficient rats and subsequently in their
newborn pups. This supplementation was beneficial, since it reduced pup mortality,
increased mean litter size and maintained appetite throughout two thirds of the
gestation period. Consequently, gamma-linolenic acid seems to correct some of the
biological effects of zinc deficiency. It is suggested that evening primrose oil could be
used in cases of zinc deficiency caused by metabolic disturbances.
Effects of gamma-linolenic acid supplementation
on pregnant rats fed a zinc-deficient diet
Ann Nutr Metab. 1987;31(5):312-9.

A double-blind trial of essential fatty acid
supplementation in patients with tardive dyskinesia
Psychiatry Res. 1989 Mar;27(3):313-23.
K S Vaddadi 1 , P Courtney, C J Gilleard, M S Manku, D F Horrobin
PMID: 2565585 DOI: 10.1016/0165-1781(89)90146-7
Abstract
This study reports the results of a trial of essential fatty acid (EFA) supplementation in psychiatric patients
(predominantly schizophrenics) with movement disorders. Evidence of EFA deficiency in these patients was observed.
The antidyskinetic effect of EFA supplementation was marginally significant but not clinically important. However,
active treatment produced highly significant improvements in total psychopathology scores and schizophrenia subscale
scores, and a significant improvement in memory.
Methods
Subjects and Drugs. We undertook a controlled trial of EFA supplementation in the form of Efamol capsules, each
capsule containing 72% linoleic acid and 9% y-linolenic acid, in psychiatric patients with established movement
disorders who had been exposed to neuroleptics over a long period of time…

[Action of evening primrose oil on cardiovascular
risk factors in insulin-dependent diabetics]
Clin Ter. 1989 Jun 15;129(5):381-8.
[Article in Italian]
R Uccella, A Contini, M Sartorio
PMID: 2548804
Abstract
In an open study, the authors compared two groups of insulin-dependent diabetics
matched for age and metabolic control, one of which was given a linoleic-gamma-linolenic
acid mixture (3 g daily), the other served as control. The effect, attributed to gamma-
linolenic acid only, was evaluated as explained in the text and is shown in the table. At the
end of two months no change was found in the control group while favorable changes of
HDL-cholesterol and platelet adhesiveness were observed in the experimental group.

Essential fatty acid treatment--effects on nerve conduction,
polyol pathway and axonal transport in streptozotocin diabetic rats
Diabetologia. 1989 Sep;32(9):655-9.doi: 10.1007/BF00274252
D R Tomlinson 1 , J P Robinson, A M Compton, P Keen
PMID: 2477293 DOI: 10.1007/BF00274252
Abstract:
This study was designed to examine the effect of dietary supplementation with essential fatty acids (evening
primrose oil--5% weight: weight added to the diet) on acute neurophysiological and neurochemical defects in
streptozotocin-diabetic rats. Diabetic rats, which were not given evening primrose oil, showed highly significant
elevations of nerve sorbitol and fructose combined with a depletion of nerve myo-inositol. In those animals there
was also a 40% reduction (p less than 0.02) in the accumulation of axonally transported substance P-like
immunoreactivity proximal to a 12 h sciatic nerve ligature together with reduced motor nerve conduction velocity
(13% [p less than 0.001] and 20% [p less than 0.001] in two separate experiments). Treatment of other diabetic
rats with evening primrose oil prevented completely the development of the motor nerve conduction velocity
deficit without affecting sorbitol, fructose or myo-inositol levels or the deficit in axonal transport of substance P. In
a second experiment, treatment of diabetic rats with evening primrose oil was associated with significant
attenuation of the conduction velocity deficit, but not complete prevention.

G A Jamal 1 , H Carmichael
PMID: 2159860 DOI: 10.1111/j.1464-5491.1990.tb01397.x
Abstract
Twenty-two patients with distal diabetic polyneuropathy confirmed both clinically and by objective nerve function
studies, completed a double-blind, placebo-controlled study to assess the effect of dietary supplementation with
gamma-linolenic acid on their neuropathy. Patients received either 360 mg gamma-linolenic acid (12 patients) or
indistinguishable placebo capsules (10 patients) for 6 months. All patients were assessed at the beginning and end of
the study period by neuropathy symptom and sign scoring, motor and sensory nerve conduction studies, and
thermal threshold measurements. When compared with the placebo group, patients on gamma-linolenic acid
showed statistically significant improvement in neuropathy symptom scores (p less than 0.001), median nerve motor
conduction velocity (p less than 0.01) and compound muscle action potential amplitude (p less than 0.01), peroneal
nerve motor conduction velocity (p less than 0.05) and compound muscle action potential amplitude (p less than
0.05), median (p less than 0.01) and sural (p less than 0.001) sensory nerve action potential amplitude and ankle
heat threshold (p less than 0.001) and cold threshold (p less than 0.01) values. gamma-Linolenic acid therapy might
have a useful role in the prevention and treatment of distal diabetic polyneuropathy.
The effect of gamma-linolenic acid on human diabetic
peripheral neuropathy: a double-blind placebo-controlled trial
Diabet Med. 1990 May;7(4):319-23.

N S Gardiner 1 , J R Duncan
PMID: 1650000 DOI: 10.1016/0952-3278(91)90149-y
Abstract
This study examined the effects of linoleic acid (LA) and gamma-linolenic acid (GLA) on BL6 melanoma
growth in cell culture and of safflower oil (SFO) which contains LA and evening primrose oil (EPO) which
contains GLA, on melanoma growth when grown in mice. The delta-6-desaturase activity of the melanoma
cells in the two systems was also examined and an attempt made to relate the activity of the enzyme to the
effects of GLA on cell and tumour growth. LA and GLA were found to be equipotent in inhibiting growth of
the in vitro cultured BL6 cells which were found to contain an appreciable level of delta-6-desaturase
activity. EPO was however found to be a more potent promoter of in vivo melanoma growth in mice than
SFO. Melanomas grown in mice were found to lack delta-6-desaturase activity suggesting that the EPO diet,
by providing GLA, was able to compensate for the loss of enzyme activity in the melanomas. The possibility
that melanomas in mice have a requirement for GLA for growth while in in vitro cultured cells excess GLA
inhibits the growth of the cells through an increase in lipid peroxidation is discussed.
Possible involvement of delta-6-desaturase in control of
melanoma growth by gamma-linolenic acid
Prostaglandins Leukot Essent Fatty Acids. 1991 Mar;42(3):149-53.

P L Biagi 1 , A Bordoni, S Hrelia, M Celadon, D F Horrobin
PMID: 1674661 DOI: 10.1016/0005-2760(91)90041-f
Abstract
We have recently demonstrated that in rats the process of delta 6-desaturation of linoleic and alpha-linolenic acids slows with aging. One
method of counteracting the effect of slowed desaturation of linoleic acid would be to provide the 6-desaturated metabolite, gamma-
linolenic acid (18:3(n-6) GLA) directly. We have here investigated the 6-desaturation of both linoleic and alpha-linolenic acids in liver
microsomes of young and old rats given GLA in the form of evening primrose oil (EPO) (B diet) in comparison to animals given soy bean oil
alone (A diet), monitoring also the fatty acid composition of liver microsomes and relating this to the microviscosity of the membranes. In
young rats the different experimental diets did not produce any difference in delta 6-desaturase (D6D) activity on either substrate suggesting
that, when D6D activity is at or near its peak, the variations in diet tested are unable to influence it. In the old animals the rate of 6-
desaturation of linoleic and particularly of alpha-linolenic acid was significantly greater in the B diet fed animals than in the A diet fed. The
effects of the diets on the fatty acid composition of liver microsomes were consistent with the findings with regard to 6-desaturation.
Administration of GLA partially corrected the abnormalities of n-6 essential fatty acid (EFA) metabolism by raising the concentration of
20:4(n-6) and other 6-desaturated EFAs. Furthermore, the GLA rich diet also increased the levels of dihomo-gamma-linolenic acid and of 6-
desaturated n-3 EFAs in the liver microsomes. The microviscosity of microsomal membranes as indicated by DPH polarization was correlated
with the unsaturation index of the same membranes. There was a very strong correlation between the two. In both young and old rats the B
diet reduced the microviscosity and increased the unsaturation index. However, the effect was much greater in the old animals.
Gamma-linolenic acid dietary supplementation can reverse the
aginginfluenceonratlivermicrosomedelta6-desaturaseactivity.
Biochim Biophys Acta. 1991 May 8;1083(2):187-92.

A Cant 1 , J Shay, D F Horrobin
PMID: 1668100 DOI: 10.3177/jnsv.37.573
Abstract
Total fat content and therefore total energy content and the content of essential fatty acids (EFAs) in milk
are known to decline with prolonged breast feeding. In a placebo-controlled study a variety of evening
primrose oil (Efamol) rich in linoleic and gamma-linolenic acids, or a matching placebo were given to 39
women for a period of 8 months starting between the 2nd and 6th months of lactation. Total fat and EFA
contents of the milk declined in the placebo group but rose in the primrose oil supplemented group. A
surprisingly high proportion of the supplemented dietary fatty acids could be accounted for by appearance
in the milk. The milk composition can be readily manipulated by changing the fatty acid composition of the
maternal diet.
The effect of maternal supplementation with linoleic and
gamma-linolenic acids on the fat composition and content
of human milk: a placebo-controlled trial
J Nutr Sci Vitaminol (Tokyo). 1991 Dec;37(6):573-9.

B B Oon 1 , D Muggleston, A Warley
PMID: 1543584 DOI: 10.1113/expphysiol.1992.sp003572
Abstract
Blood glucose, circulating lymphocyte numbers, and the percentage of T- and B-lymphocytes were
measured in diabetic and non-diabetic rats which had been fed on control diets, or diets which
included oil of evening primrose or coconut oil. In diabetic animals fed on the control or coconut oil
diet the number of circulating lymphocytes decreased; this was caused by a decrease in both T- and
B-lymphocytes. The decreases in lymphocyte numbers was less in the diabetic animals fed on the
diet enriched in evening primrose oil. In these animals the decrease in T-lymphocytes was less and
the percentage of B-lymphocytes was increased. It is suggested that the diet enriched in evening
primrose oil exerts its protective effect by providing gamma-linolenic acid which is necessary for
biosynthesis of prostaglandin E1.
A diet enriched in essential fatty acids protects
against the loss of lymphocytes which occurs in rats
suffering from streptozotocin-induced diabetes
Exp Physiol. 1992 Jan;77(1):185-90.

G Ramesh 1 , U N Das, R Koratkar, M Padma, P S Sagar
PMID: 1330107
Abstract
An earlier study showed that essential fatty acids and their metabolites can kill tumor cells in
vitro. This tumoricidal action can be correlated to an increase in generation of free radicals in
the tumor cells. Evening primrose oil (EPO) is a rich source of linoleic acid and gamma-linolenic
acid. We report that EPO can kill tumor cells both in vitro and in vivo. This tumoricidal action
of EPO was associated with a threefold increase in superoxide generation. One of the factors
that is capable of interfering with the cytotoxic action of fatty acids appears to be the protein
content of the medium. Fatty acids can bind to protein and thus prevent their cytotoxic action.
Effect of essential fatty acids on tumor cells
Nutrition. Sep-Oct 1992;8(5):343-7.

D F Horrobin 1Affiliations
PMID: 8380930 DOI: 10.1016/0952-3278(93)90016-p
Abstract
Gamma-linolenic acid (GLA) has recently been found to be beneficial in the management of
breast pain and of diabetic neuropathy. GLA is a precursor of unsaturated fatty acids which
are important in membrane structures, as second messengers in their own right and as
precursors of eicosanoids. While the mechanisms of GLA action are likely to be complex,
non-eicosanoid effects are probably of substantial importance. These effects include
modification of membrane fluidity and of the functions of lipid-associated receptors and
changes in the inositol cycle.
The effects of gamma-linolenic acid on breast pain and
diabetic neuropathy: possible non-eicosanoid mechanisms
Prostaglandins Leukot Essent Fatty Acids. 1993 Jan;48(1):101-4.

P C Calder 1Affiliations
PMID: 8298526
Abstract
1. Lymphocytes play an important role in cell-mediated immunity and have been implicated in inflammatory and autoimmune
diseases. 2. Unsaturated fatty acids, including oleic, linoleic, alpha-linolenic, arachidonic, eicosapentaenoic and
docosahexaenoic acids, inhibit mitogen-stimulated lymphocyte proliferation in vitro. The inhibition of proliferation is
dependent upon the concentration of fatty acid, the time during culture of fatty acid addition, the duration of exposure of the
cells to the fatty acid and the chain length and degree of unsaturation of the fatty acid. 3. Unsaturated fatty acids suppress
production of the immunoregulatory cytokine interleukin-2 by lymphocytes in vitro. 4. Triacylglycerols containing unsaturated
fatty acids inhibit lymphocyte proliferation and natural killer cell activity in vitro. 5. Feeding weanling rats diets containing olive
oil, evening primrose oil or fish oil results in suppression of lymphocyte proliferation. 6. Preliminary studies indicated that
supplementation of the diet of healthy humans with fish oil-containing capsules suppresses lymphocyte proliferation and
interleukin-2 production. 7. These effects, along with inhibitory effects upon the functions of other cells involved in the
immune response, in particular monocytes and macrophages, indicate that certain unsaturated fatty acid-containing oils
(particularly evening primrose oil and fish oil) may be of benefit in the treatment of inflammatory and autoimmune diseases.
The effects of fatty acids on lymphocyte functions
Braz J Med Biol Res. 1993 Sep;26(9):901-17.

[Influence of evening primrose oil on blood pressure
and the pressor response to angiotensin II in
pregnant and non-pregnant rabbits]
Ginekol Pol. 1994 Mar;65(3):111-4.
[Article in Polish]
M Zieliński 1 , L Wojnarski, Z Celewicz, A Cretti
PMID: 8001843
Abstract
Evening primrose oil was given through a intragastric catheter in dose of 50 mg/kg day for 10 days to pregnant (8
animals) and nonpregnant (8 animals) rabbits. Control groups contained 8 pregnant and 8 nonpregnant animals.
In the acute experiment we estimated directly (intraarterially) basal blood pressure and pressor response to
angiotensin II (A II). The systolic and diastolic response to A II was significantly lower in pregnant rabbits which
received evening primrose oil compared to control group. No significant effect was found in the nonpregnant
groups. Basal (before A II) systolic and diastolic blood pressure did not differ between the treated and untreated
subject in each group.

The effect of gamma-linolenic acid on clinical status, red cell
fatty acid composition and membrane microviscosity in infants
with atopic dermatitis
Drugs Exp Clin Res. 1994;20(2):77-84.
P L Biagi 1 , A Bordoni, S Hrelia, M Celadon, G P Ricci, V Cannella, A Patrizi, F Specchia, M Masi
PMID: 7924900
Abstract
A double blind placebo-controlled study of two doses of gamma-linolenic acid, provided by evening primrose oil (EPO, Epogam, Searle,
U.K.), in children with atopic dermatitis was performed: 1) to examine the effect of gamma-linolenic acid administration on the clinical
status of children with atopic dermatitis and abnormalities of IgE-mediated immune responses compared to those without such IgE
abnormalities; 2) to investigate the effect of gamma-linolenic acid on red cell fatty acid composition and 3) to assess whether
treatment with gamma-linolenic acid induced changes in red cell membrane microviscosity. A significant improvement in the overall
severity of the clinical condition was seen in children treated with gamma-linolenic acid, independent of whether the children had
manifestations of IgE-mediated allergy. Furthermore, gamma-linolenic acid treatment increased the percentage content of n-6 fatty
acids in erythrocyte cell membrane; this increase was more marked in the membranes of children treated with high doses of EPO. In
the high dose group a significant increase in dihomogamma-linolenic acid (DGLA) occurred. This may be of particular relevance because
of the potential importance of DGLA as a precursor of antiinflammatory prostanoids. Red cell membrane microviscosity did not change
in any group after treatment with EPO, even in high doses, despite a significant increase in the proportion of long chain
polyunsaturated fatty acids.

Effects of anti-oxidant treatment on sciatic nerve dysfunction in
streptozotocin-diabetic rats; comparison with essential fatty acids
Diabetologia. 1995 Feb;38(2):129-34.
C Karasu 1 , M Dewhurst, E J Stevens, D R Tomlinson
PMID: 7713308 DOI: 10.1007/BF00400086
Abstract
In Study 1, the effects of treatment of streptozotocin-diabetic rats with the antioxidants, probucol or vitamin E were compared.
Untreated diabetic rats showed a reduction of 45% (p < 0.01) in nerve laser Doppler flux, which was used as an index of nerve
blood flow. In diabetic rats treated with either probucol or vitamin E nerve Doppler flux was reduced by only 13 or 16%,
respectively (p < 0.01 for either compared to untreated diabetic rats). A second study examined the effects of treatment with
evening primrose oil either alone or in combination with probucol. Reduced nerve Doppler flux was reproduced in untreated
diabetic rats (47%; p < 0.01). In parallel diabetic groups, nerve Doppler flux was reduced by only 14% with evening primrose oil
alone and by 8% with evening primrose oil plus probucol (both p < 0.01 vs untreated diabetic rats). Both treatments were also
associated with marked attenuation of motor and sensory nerve conduction velocity deficits. Measurements on plasma from
rats showed normalisation of triglyceride levels by probucol treatment without an effect on those of cholesterol in Study 1. In
Study 2, the converse was true for evening primrose oil treatment, whilst the combined treatment lowered both plasma
triglycerides and cholesterol. This work indicates similar effects of antioxidants and evening primrose oil against reduced nerve
Doppler flux and conduction velocity in diabetic rats, with dissimilar actions on plasma triglycerides and cholesterol.

Comparison of the effects of ascorbyl gamma-linolenic acid and gamma-
linolenic acid in the correction of neurovascular deficits in diabetic rats
Diabetologia. 1996 Sep;39(9):1047-54.
N E Cameron 1 , M A Cotter
PMID: 8877288 DOI: 10.1007/BF00400653
Abstract
Essential fatty acid metabolism is impaired by diabetes mellitus and gamma-linolenic acid rich treatments such as evening
primrose oil correct deficits in nerve conduction and endoneurial blood flow in diabetic rats. Other mechanistically unrelated
treatments, such as antioxidants and aldose reductase inhibitors have a similar effect and there may be positive interactions with
multiple treatments. Our aim was to compare the efficacy of a novel essential fatty acid derivative, ascorbyl gamma-linolenic acid,
with that of gamma-linolenic acid in correcting diabetic neurovascular deficits. Eight weeks of diabetes caused 20.4 and 48.2%
reductions in sciatic motor conduction velocity and nutritive endoneurial blood flow, respectively. Treatment was given for the last
2 weeks with gamma-linolenic acid (100 mg.kg-1.day-1) either in pure form or as ascorbyl gamma-linolenic acid, an equivalent
dose of ascorbate (21 mg.kg-1.day-1) or jointly with ascorbate and gamma-linolenic acid. Conduction velocity was corrected by
39.8, 87.4, 13.2 and 66.8% with gamma-linolenic acid, ascorbyl gamma-linolenic acid, ascorbate and gamma-linolenic acid plus
ascorbate, respectively. Corresponding ameliorations of the nutritive blood flow deficit were 44.0, 87.4, 87.4, 13.2 and 65.7%. For
the gamma-linolenic acid plus ascorbate combinatin, and especially for ascorbyl gamma-linolenic acid, the magnitude of
correction for conduction velocity and blood flow was greater than expected for simple addition of ascorbate and gamma-
linolenic acid, indicating a synergistic interaction. Thus, with an efficacy 40 times that of evening primrose oil in rats, ascorbyl
gamma-linolenic acid may be a suitable candidate for clinical trials of diabetic neuropathy.

Effects of dietary supplementation with arachidonic acid rich oils on
nerve conduction and blood flow in streptozotocin-diabetic rats
Prostaglandins Leukot Essent Fatty Acids. 1997 May;56(5):337-43.
M A Cotter 1 , N E Cameron
PMID: 9175169 DOI: 10.1016/s0952-3278(97)90581-0
Abstract
Diabetes mellitus is associated with defective essential fatty acid desaturation. In experimental models this contributes to
characteristic reductions in peripheral nerve conduction velocity (NCV) and blood flow, which may be corrected by dietary
supplementation with gamma-linolenic acid (GLA) rich oils to bypass the delta-6 desaturation deficit. There is debate about
the mechanism of this improvement, including whether it depends on synthesis of series 1 prostanoids derived from di-homo
GLA or series 2 prostanoids from arachidonic acid (ARA). The aim was to assess the efficacy of two ARA-rich (approximately
39% content) oils in correcting neurovascular dysfunction in streptozotocin-induced diabetic rats. After 6 weeks of untreated
diabetes, rats were treated for a further 2 weeks with 1% dietary oil supplements before assessment of sciatic motor NCV
and endoneurial blood flow. NCV was 19% reduced in diabetic rats and this was largely (approximately 86%) corrected by
both oil treatments. A 48% deficit in endoneurial nutritive blood flow with diabetes was approximately 70% reversed by the
two oils, vascular conductance being in the non-diabetic range. Thus, nerve conduction and perfusion deficits in diabetic rats
are corrected by ARA-rich oil treatment. The magnitudes of these changes were similar to expectations based on previous
studies of GLA-rich oils, therefore it is likely that the neurovascular effect of increased synthesis of series 2 prostanoids makes
a major contribution to the beneficial action of n-6 essential fatty acids in experimental diabetic neuropathy.

Differential effects of dietary Oenothera, Zizyphus mistol,
and corn oils, and essential fatty acid deficiency on the
progression of a murine mammary gland adenocarcinoma
Nutrition. 1999 Mar;15(3):208-12.
S E Muñoz 1 , M Piegari, C A Guzmán, A R Eynard
PMID: 10198915 DOI: 10.1016/s0899-9007(98)00181-6
Abstract
The modulating effect of dietary enrichment in mistol seed oil (MO) containing 25% of alpha-linolenic acid (ALA), evening
primrose oil (EPO) enriched in gamma-linolenic acid (GLA) and corn oil (CO) as sources of omega-6 and omega-9 fatty acids on
the growth parameters of one transplantable mammary tumor were compared. Mice fed on different lipid formulae were
inoculated with a mammary gland adenocarcinoma and different growth development tumor parameters were recorded.
Results showed that corn oil feeding slowed down most of the tumor growth parameters, as did the EPO diet. MO also
showed antitumor activity. Olein feeding, which induces an essential fatty acid deficiency (EFAD), increased the incidence and
the multiplicity of metastases when compared with the controls. It may be concluded that a diet enriched in omega-6 fatty
acids did not behave as a tumor promoter in this mammary gland tumor model. The antitumor activities of EPO and MO are
corroborated in present experiments, suggesting that both oils may be of value in nutritional approaches of mammary gland
tumor therapies. In addition, present data add further experimental proof about the proposed protumorigenic proneness
induced by the EFAD state.

Cytokine levels affected by gamma-linolenic acid
Prostaglandins Leukot Essent Fatty Acids. 1998 Oct;59(4):273-7.
J Dirks 1 , C H van Aswegen, D J du Plessis
PMID: 9849654 DOI: 10.1016/s0952-3278(98)90141-7
Abstract
This study was undertaken to assess whether gamma-linolenic acid (GLA) in the form of evening
primrose oil (EPO) could affect rat serum cytokines, interferon-gamma (IFN-gamma), monocyte
chemotactic protein-1 (MCP-1) and tumour necrosis factor-alpha (TNF-alpha). The following
diets were administered: control, glucan, Freund's adjuvant and glucan plus Freund's adjuvant
with and without GLA. In the presence of GLA, the IFN-gamma and MCP-1 levels were
significantly decreased in contrast to the control group of TNF-alpha, which was significantly
stimulated. On account of interaction between diets and GLA, the remaining diet groups of TNF-
alpha were either not affected or were inhibited in the presence of GLA. The observations
indicate that GLA may modulate the level of serum IFN-gamma, MCP-1 and TNF-alpha, which
may be a worthwhile line of treatment in certain human diseases.

Gamma-linolenic acid provides additional protection against
ventricular fibrillation in aged rats fed linoleic acid rich diets
Prostaglandins Leukot Essent Fatty Acids. 2000 Feb;62(2):129-34.
J S Charnock
PMID: 10780878 DOI: 10.1054/plef.1999.0132
Abstract
Ligation of the coronary artery in rats produces severe ventricular fibrillation (VF) and malignant cardiac
arrhythmia. Mortality increases with the age of the animal. Diets rich in saturated fatty acids (SF) but low in
linoleic acid (LA) increase, but diets high in LA and low in SF decrease the severity of VF and mortality in older
animals. The effects of an LA enriched diet can be blocked by inhibition of cyclooxygenase suggesting that
conversion of LA to eicosanoids is central to the development of VF. Conversion of LA to gamma-linolenic acid
(GLA) via delta-6 desaturase is the first step in the process. The activity of delta-6 desaturase declines with age.
Thus inclusion of GLA in the diet of older animals may provide an additional benefit over LA alone. Dietary
supplements of evening primrose oil (EPO) to one year old rats reduced ischaemic VF more than a supplement
of sunflower seed oil (SSO) without GLA. Substitution of borage oil (more GLA than EPO but less LA than either
EPO or SSO) was without additional benefit.

The effect of gamma-linolenic acid on plasma and membrane
lipids and renal prostaglandin synthesis in older subjects
Bratisl Lek Listy. 2002;103(3):101-7.
A Hornych 1 , S Oravec, F Girault, B Forette, D F Horrobin
PMID: 12190041
Abstract
Senescence is associated with a decreased activity of enzyme delta-6 desaturase, which converts linoleic acid to
gamma-linolenic acid. This enzymatic defect may alter the composition of plasma and membrane lipids, and
influences the biosynthesis of renal prostaglandins. Exogenous supplementation of GLA during 3 months increases
the plasma level of dihomo-gamma-linolenic acid (p < 0.002), and to a smaller degree, the level in erythrocyte
membrane lipids. This treatment was associated with a beneficial reduction of cardiovascular risk factors (arterial
hypertension, total cholesterol, apolipoprotein B, HDL-cholesterol, apolipoprotein A-I) and the renal function has
become stable reached. Epogam treatment also increased the biosynthesis of renal prostaglandins, especially that
of prostaglandin E2, which has a vasodilatory effect on vessel walls and reduces the elevated blood pressure.
Conclusion: Dietary supplementation of essential fatty acids such as gamma-linolenic acid to old subjects has
beneficial effect on their health condition. (Tab. 6, Fig. 5, Ref. 37.)

Botanicals and dietary supplements in diabetic peripheral neuropathy
J Am Board Fam Pract . Jan-Feb 2003;16(1):47-57.doi: 10.3122/jabfm.16.1.47.
PMID: 12583650 DOI: 10.3122/jabfm.16.1.47
Kathleen M Halat 1 , Cathi E Dennehy
Abstract
Background: Many persons use botanicals and dietary supplements for chronic conditions that do not respond to
traditional Western medications. Tricyclic antidepressants, a common treatment option for diabetic neuropathy, can
have many side effects and are a poor choice in certain populations (eg, the elderly). As such, patients might turn to
botanicals and dietary supplements, not realizing that these products are not well regulated.
Methods: This article reviews botanicals and dietary supplements that have been involved in randomized controlled
trials (RCTs) for diabetic neuropathy. We searched MEDLINE for English-language literature dating from 1966 to April
2001 using the following subject headings: (1) diabetes and botanical, herb, and supplement, (2) neuropathy and
botanical, herb, and supplement, and (3) diabetic neuropathy and botanical, herb, and supplement.
Results: Our search found agents that might improve symptoms of neuropathy (eg, evening primrose oil, alpha-lipoic
acid, capsaicin) without affecting glucose control. Botanicals and dietary supplements involved in only one RCT or
associated with little clinical benefit were reviewed in brief.
Conclusions: Evening primrose oil, alpha-lipoic acid, and capsaicin have received the greatest attention for their use in
diabetic neuropathy, but further studies are needed to confirm their efficacy. Patients using these products need to be
informed of potential drug interactions and side effects.

Effects of different dietary oils on inflammatory mediator generation
and fatty acid composition in rat neutrophils
Metabolism. 2004 Jan;53(1):59-65.
R de La Puerta Vázquez 1 , E Martínez-Domínguez, J Sánchez Perona, V Ruiz-Gutiérrez
PMID: 14681843 DOI: 10.1016/j.metabol.2003.08.010
Abstract
Virgin olive oil (VOO) compared with fish oil (FO) and evening primrose oil (PO) on the ability of stimulated leukocytes to produce
inflammatory mediators was investigated in rats. Weaned Wistar rats were fed a basal diet (BD) (2% by weight of corn oil) or diets
containing 15% by weight of VOO, PO, or FO. After 8 weeks, glycogen-elicited peritoneal polymorphonuclear leukocytes, mainly
neutrophils, were isolated. The calcium-ionophore stimulated neutrophils (2.5 x 10(6) cells/mL) obtained from rats fed the different
oils produced a higher release of lysosomal enzymes (beta-glucuronidase, lysozyme, and myeloperoxidase [MPO]) compared with
those fed BD. The production of reactive oxygen species (ROS) in response to the stimulant, 12-O-tetradecanoyl-phorbol-13-
acetate (TPA), by neutrophils from the VOO group (15.44 nmol of O(2)(-) and 6.56 nmol of H(2)O(2)) was similar to the BD group
(12.01 nmol O(2)(-) and 8.49 nmol H(2)O(2)) and significantly lower than the PO (20.90 nmol O(2)(-) and 10.84 nmol H(2)O(2)) and
FO (20.93 nmol O(2)(-) and 12.79 nmol H(2)O(2)) groups. The cyclooxygenase-derived eicosanoid production was reduced by the
lipid enrichment of the diets. Whereas the generation of prostaglandin E(2) (PGE(2)) was significantly decreased in VOO (5.40
ng/mL), PO (4.95 ng/mL), and FO (1.44 ng/mL) groups compared with BD (8.19 ng/mL), thromboxane B(2) (TXB(2)) reduction was
especially significant in neutrophils from the FO diet group (14.67 ng/mL compared with 26.69 ng/mL from BD). These
experimental data suggest that FO and PO, as well as VOO, could be considered a valuable strategy in preventing the generation of
some inflammatory mediators.

Prevention and partial reversal of diabetes-induced changes in enteric
nerves of the rat ileum by combined treatment with alpha-lipoic acid
and evening primrose oil
Auton Neurosci. 2004 Mar 31;111(1):57-65.
Hannah R Shotton 1 , Steven Broadbent, Jill Lincoln
PMID: 15109939 DOI: 10.1016/j.autneu.2004.02.004
Abstract
Treatment with alpha-lipoic acid (LA) or evening primrose oil (EPO), individually, fails to prevent diabetes-induced changes in enteric
nerves. Since synergy between these treatments has been reported, the aim was to investigate the effectiveness of combined LA/EPO
treatment. LA and EPO were administered in the diet (approximately 80 and 200 mg/kg/day, respectively) to control and diabetic
(induced by streptozotocin, 65 mg/kg, i.p.) rats. For prevention, treatment started after 1 week and lasted 7 weeks. For reversal,
treatment lasted 4 weeks and was initiated after 8 weeks. Nerves supplying the ileum containing vasoactive intestinal polypeptide
(VIP), calcitonin gene-related peptide (CGRP) and noradrenaline (NA) were examined immunohistochemically or biochemically.
Diabetes caused a significant increase in VIP-containing cell bodies (p<0.001), decrease in NA content (p<0.01) and loss of CGRP-
immunoreactivity. LA/EPO treatment totally prevented diabetes-induced changes in VIP (p<0.001) and CGRP and partially reversed
(p<0.05) these changes once they had been allowed to develop. In contrast, treatment had no effect on diabetes-induced changes in
NA-containing nerves. Therefore, LA and EPO are only effective at treating diabetes-induced changes in some enteric nerves when
administered in combination. However, diabetes-induced changes in NA-containing nerves are resistant to treatment.

A 5-month open study with long-chain polyunsaturated
fatty acids in dyslexia
J Med Food. 2007 Dec;10(4):662-6.
Lars Lindmark 1 , Peter Clough
PMID: 18158838 DOI: 10.1089/jmf.2006.399
Abstract
This open pilot study investigated effects of a docosahexaenoic acid (DHA)-rich supplement on learning ability in a group of 20
dyslexic children in Sweden. Children formally diagnosed as dyslexic took eight capsules per day of a long-chain
polyunsaturated fatty acid (LC-PUFA) supplement containing high-DHA fish oil and evening primrose oil. Subjective
assessments by the children and their parents were completed at baseline and 6, 12, and 20 weeks after supplementation.
Quantitative evaluation by word-chain test was completed before and after 4 months of supplementation to measure word
decoding (speed of reading) and letter decoding (motoric-perceptual speed). Subjective parent and child assessments showed
increasing numbers of positive responders over time in reading speed, general schoolwork, and overall perceived benefit.
Significant improvements were observed in reading speed and motor-perceptual velocity. Thirteen of 17 children had a
significant improvement on the word-chain test (P < .04). Reading speed improved by 60% from 1.76 +/- 0.29 before the study
to 2.82 +/- 0.36 after supplementation (P < .01 by Wilcoxon sign test). Motoric-perceptual velocity improved by 23% from a
stanine value of 3.76 +/- 0.42 to 4.65 +/- 0.66 after supplementation (P < .05 by Wilcoxon sign test). Thus LC-PUFA
supplementation for 5 months provides positive and clear beneficial effect on variables usually impaired by dyslexia.

Oral omega-6 essential fatty acid treatment in
contact lens associated dry eye
Cont Lens Anterior Eye. 2008 Jun;31(3):141-6; quiz 170. Epub 2008 Mar 4.
Karolien H Kokke 1 , Judith A Morris, John G Lawrenson
PMID: 18313350 DOI: 10.1016/j.clae.2007.12.001
Abstract
Purpose: Symptoms of dry eye are commonly reported in contact lens wearers and are a frequent cause of non-tolerance. The purpose
of the present study is to evaluate the effects of oral treatment with particular omega-6 fatty acids in the form of evening primrose oil
(EPO) on subjective symptoms, ocular surface signs and tear film characteristic in patients with contact lens associated dry eye.
Methods: The study design was randomised, double-masked and placebo controlled. 76 female soft contact lens wearers were treated
for 6 months with either EPO or placebo (olive oil). Subjects underwent three examinations (baseline, 3 and 6 months). At each
examination subjects were given a questionnaire relating to lens comfort and dry eye symptoms and underwent a series of tests of
tear film characteristics (tear meniscus height, break-up time), meibomian gland function (lipid layer thickness and quality) and ocular
surface parameters (hyperaemia and staining).
Results: The EPO group showed a significant improvement in the specific symptom of 'dryness' at 3 and 6 months (p<0.01) and also a
significant improvement in overall lens comfort at 6 months (p<0.01). Tear meniscus height was increased in the EPO group at 6
months relative to baseline (p<0.01), although all other objective signs were unchanged.
Conclusion: This study provides evidence for a beneficial effect of particular orally administered omega-6 fatty acids in alleviating dry
eye symptoms and improving overall lens comfort in patients suffering from contact lens associated dry eye.

Femicomfort in the treatment of premenstrual syndromes:
a double-blind, randomized and placebo-controlled trial
Iran J Psychiatry. Spring 2010;5(2):47-50.
Ladan Kashani 1 , Nafiseh Saedi, Shahin Akhondzadeh
PMID: 22952490 PMCID: PMC3430493
Abstract
Objective: Premenstrual syndromes (PMS) affecting 20-40% of women of reproductive age. The aim of this double blind and placebo
controlled trial was to investigate whether femicofort a supplement contains Vitamin B6, Vitamin E and evening primrose oil could
relieve symptoms of PMS.
Method: This was a randomized and double blind clinical trial. The trial was conducted between November 2009 and April March 2010.
Women aged 20 to 45 years with regular menstrual cycles and experience of PMS symptoms (According to the current diagnostic
criteria proposed by the American College of Obstetrics and Gynecology) for at least 6 months were eligible for the study. Patients were
randomized to receive femicomfort or placebo in a 1: 1 ratio using a computer-generated code. The assignments were kept in sealed,
opaque envelopes until the point of analysis of data. In this double-blind, patients were randomly assigned to receive capsule of
femicomfort (Group A) or capsule placebo for two menstrual cycles (cycles 3 and 4). The primary outcome measure was the Daily
Symptom Report, a checklist of 17 premenstrual symptoms rated from 0 to 4 according to their severity throughout the menstrual
cycle. Secondary outcome measure was Hamilton Depression Rating Scale (17-item).
Results: Femicomfort at this dose was found to be effective in relieving symptoms of PMS. The difference between the femicomfort and
placebo in the frequency of side effects was not significant.
Conclusion: The results of this study indicate the efficacy of femicomfort in the treatment of PMS.

Herbal therapy for treating rheumatoid arthritis
Cochrane Database Syst Rev. 2011 Feb 16;(2):CD002948.
Melainie Cameron 1 , Joel J Gagnier, Sigrun Chrubasik
PMID: 21328257 DOI: 10.1002/14651858.CD002948.pub2
Abstract
Background: Herbal medicine interventions have been identified as having potential benefit in the treatment of rheumatoid arthritis (RA).
Objectives: To update an existing systematic (Cochrane) review of herbal therapies in RA.
Main results: Twelve new studies were added to the update, a total of 22 studies were included. Evidence from seven studies indicate potential
benefits of gamma linolenic acid (GLA) from evening primrose oil, borage seed oil, or blackcurrent seed oil, in terms of reduced pain intensity
(mean difference (MD) -32.83 points, 95% confidence interval (CI) -56.25 to -9.42,100 point pain scale); improved disability (MD -15.75% 95% CI -
27.06 to -4.44%); and an increase in adverse events (GLA 20% versus placebo 3%), that was not statistically different (relative risk 4.24, 95% CI
0.78 to 22.99). Three studies compared Tripterygium wilfordii (thunder god vine) to placebo and one to sulfasalazine and indicated
improvements in some outcomes, but data could not be pooled due to differing interventions, comparisons and outcomes. One study reported
serious side effects with oral Tripterygium wilfordii Hook F. In the follow-up studies, all side effects were mild to moderate and resolved after the
intervention ceased. Two studies compared Phytodolor(®) N to placebo but poor reporting limited data extraction. The remaining studies each
considered differing herbal interventions.
Authors' conclusions: Several herbal interventions are inadequately justified by single studies or non-comparable studies in the treatment of
rheumatoid arthritis. There is moderate evidence that oils containing GLA (evening primrose, borage, or blackcurrant seed oil) afford some benefit
in relieving symptoms for RA, while evidence for Phytodolor® N is less convincing. Tripterygium wilfordii products may reduce some RA symptoms,
however, oral use may be associated with several side effects. Many trials of herbal therapies are hampered by research design flaws and
inadequate reporting. Further investigation of each herbal therapy is warranted, particularly via well designed, fully powered, confirmatory clinical
trials that use American College of Rheumatology improvement criteria to measure outcomes and report results according to CONSORT guidelines.

Abstract
Background: Atopic dermatitis (AD) is related to a deficiency of delta-6-desaturase, an enzyme responsible for converting linoleic
acid to gamma-linolenic acid (GLA). Evening primrose oil (EPO) as a source of GLA has been of interest in the management of AD.
Methods: FiftymildADpatientswithanEczema Area Severity Index(EASI) score of10orlesswere enrolledandrandomly dividedinto two
groups. Thefirstgroup received anovalunmarked capsulecontaining450 mgofEPO(40 mgofGLA)percapsule,whileplacebo capsules
identicalinappearanceandcontaining450 mgofsoybean oilwere giventotheother group.Treatment continuedforaperiod offour months.
EASIscores, transepidermal waterloss(TEWL), andskinhydration were evaluatedinalltheADpatientsatthebaseline,andinmonths1,2,3,
and4ofthestudy.
Results: At the end of month 4, the patients of the EPO group showed a significant improvement in the EASI score
(p=0.040), whereas the patients of the placebo group did not. There was a significant difference in the EASI score
between the EPO and placebo groups (p=0.010). Although not statistically significant, the TEWL and skin hydration also
slightly improved in the EPO patients group.
Conclusion: We suggest that EPO is a safe and effective medicine for Korean patients with mild AD.
Effect of Evening Primrose Oil on Korean Patients with Mild Atopic
Dermatitis: A Randomized, Double-Blinded, Placebo-Controlled
Clinical Study
Ann Dermatol. 2018 Aug;30(4):409-416.

Abstract
Objective: The purpose of this study was to determine the efficacy and safety of evening primrose oil on women's psychological
symptoms during menopause.
Methods: A double-blinded randomized placebo-controlled trial carried out from September 2018 to February 2019 in Bandar Abbas, Iran. Eligible
women randomly received either 1,000 mg of evening primrose oil capsules daily or matching placebo for 8 weeks. The Main outcome measures were
psychological symptoms based on the psychological subscale of the Menopause Rating Scale. Independent samples t test was used for intergroup
comparisons and paired samples t test for pre- and post-treatment comparisons. P ≤ 0.05 was considered statistically significant.
Results: The 8-week treatment was completed by 189 women. The mean baseline psychological score did not differ among the two groups.
After intervention, the psychological score, however, differed significantly among groups (P < 0.01). To distinguish the effect of evening
primrose oil, we compared the reduction in the psychological score in each group. Regarding mean differences of the psychological score in
both groups, there was a prominent alleviation in the intervention group mean difference: -3.44 (95% confidence interval of difference: -4.01
to -1.20) (P < 0.01). In addition, only one patient reported gastric upset in the intervention group.
Conclusions: This study could provide evidence regarding the potential benefits of evening primrose oil for the psychological
symptoms of postmenopausal women. Longer trials are necessary to make more reliable decisions about the use of evening primrose
oil and its safety in clinical practice.
Impact of evening primrose oil consumption on psychological
symptoms of postmenopausal women: a randomized double-
blinded placebo-controlled clinical trial
Menopause 2020 Feb;27(2):194-198.

Abstract
Background: Saturated fatty acid esters may cause mastalgia via hypersensitivity of breast epithelium to
circulating hormones. Evening primrose oil (EPO) may restore the saturated/unsaturated fatty acid balance and
decrease sensitivity to steroidal hormones or prolactin. Conflicting results exist regarding EPO treatment for
mastalgia. The aim of this study was to determine the effectiveness of EPO and factors affecting its efficacy in
treatment of mastalgia.
Results: The therapeutic efficacy of EPO on mastalgia was significantly higher than with paracetamol (p < 0.001).
Factors significantly affecting the efficacy of EPO treatment were hormone replacement therapy (HRT), IUD-with-
levonorgestrel, iron deficiency, overt hypothyroidism, and Hashimoto thyroiditis (p < 0.01). Replacement of iron
or thyroid hormone efficiently treated mastalgia in patients that did not respond to EPO treatment. Side effects
(allergy, anxiety, blurred vision, constipation, and nausea) were rare and not statistically significant (p = 0.88).
Conclusion: EPO can be used in the treatment of mastalgia without significant side effects. HRT, IUD-with-
levonorgestrel, iron deficiency, overt hypothyroidism, and Hashimoto thyroiditis significantly affect the efficacy
of EPO on mastalgia.
Clinical Factors Affecting the Therapeutic
Efficacy of Evening Primrose Oil on Mastalgia
Ann Surg Oncol. 2020 Nov;27(12):4844-4852.

Abstract
The mammalian target of rapamycin (mTOR) signaling plays a critical role in lipid synthesis and immune responses. The T regulatory cells
(Treg) as suppressor of T cells, are a subset of T cells that modulate the immune system, maintain tolerance, and prevent autoimmune
diseases.. The interleukin (IL) -10 derived from the Treg and T helper (Th) 2 is an anti-inflammatory cytokine in multiple sclerosis (MS) and
experimental autoimmune encephalomyelitis (EAE). Due to the exclusive roles of rapamycin (RAPA) in mTOR inhibition, we evaluated the
regulatory effect of the hemp seed oil/evening primrose oil (HSO/EPO) supplement in comparison with RAPA in EAE. EAE was induced by
using myelin oligodendrocyte glycoprotein peptide and complete freund's adjuvant (CFA) in C57BL/6 mice, total mRNA was extracted from
local lymph nodes and real-time polymerase chain reaction was used to evaluate the expression level of the rapamycin-insensitive
companion of mTOR complex 2 (RICTOR) and IL-10 genes. The expression of IL-10 and RICTOR genes were significantly increased in
HSO/EPO group. In contrast with RAPA groups, histological findings have shown that the HSO/EPO treated group remarkably reduced cell
infiltration and promoted remyelination. The EPO/HSO has beneficial effects on the repair of myelin, which was confirmed by
immunological and histological findings.
Regulatoryeffectsofhempseed/evening primroseoilsupplementincomparison
withrapamycinontheexpression ofthemammaliantargetofrapamycin-complex
2 and interleukin-10 genes in experimental autoimmune encephalomyelitis
Res Pharm Sci. 2019 Feb;14(1):36-45.

Abstract
T helper (Th)-17 mediate inflammation in both peripheral tissues and the central nervous system. Signal transducer and activator
of transcription factor3 (STAT3) is required for Th-cell pathogenicity and its activation in the brain has been demonstrated during
the acute phase of experimental autoimmune encephalomyelitis (EAE) through the mammalian target of rapamycin (mTOR)
signaling. Rapamycin (RAPA), an inhibitor of mTOR, can drive Forkhead box P3 (FOXP3+) induction as a regulatory factor. The aim of
this study was to determine the effects of hemp seed/evening primrose oils (HSO/EPO) supplement on the expression of FOXP3+,
STAT3, and interleukin (IL)-17 genes in EAE lymph nodes. EAE was induced by myelin oligodendrocyte glycoprotein peptide in mice,
and then the mice were assigned to three treatment groups compared to two control groups (EAE and naive). The histological
findings of the spinal cord were evaluated. To determine the expression of FOXP3+, STAT3, and IL-17 genes in the lymphocytes, qRT-
PCR was used. Our results showed that EAE severity was reduced in HSO/EPO mice by reducing the expression of STAT3 and IL-17
genes and increasing the expression of FOXP3+ gene, which was confirmed by slight inflammation in the spinal cord. Histological
findings showed a significant improvement in the HSO/EPO group. Our findings suggest that the HSO/EPO treatment can be used
to ameliorate the demyelination of spinal cord, which was confirmed by immunological and histological findings.
Hemp seed/evening primrose oil affects expression of STAT3, IL-
17, and FOXP3 + in experimental autoimmune encephalomyelitis
Res Pharm Sci. 2019 Mar 8;14(2):146-154.

Vs.
FDA
Dietary
Supplement
Consumers

Stock Photo Reenactment of FDA Raid

FDA RAIDS AGAINST SUPPLEMENTS MAKERS
Raid: Traco Labs, Inc. - November, 1988
Address: 205 S Main St. Seymour, IL 61875
Reason: FDA claimed that black currant oil was an unsafe food additive.
Outcome: FDA seized two drums of black currant oil as well as a large quantity of the capsulized product.
On Jan. 28, 1993, the U.S. Court of Appeals ruled against FDA. The judge said that FDA's definition of food
additive is too broad that even water added to food would be considered a food additive.
Raid: Life Extension® - Feb 26, 1987
Address: PO Box 229120, Hollywood, FL 33022
Reason: FDA alleged LEF was selling unapproved drugs (vitamins in U.S.) and drugs from overseas
companies.
Outcome: FDA seized $500,000 worth of vitamins, computers, files, newsletters, personal belongings.
Phones were ripped out of the walls and employees terrorized. The foundation's leaders, Saul Kent and
William Faloon, were indicted on 28 criminal counts with maximum prison time of 84 years in November
1991.

Raid: Highland Labs - Fall, 1990
Address: Box 199 Mt. Angel, OR 97362
Reason: FDA claimed that product literature was being shipped with products to customers. FDA said this made
COQ10 an unapproved drug.
Outcome: After spending $250,000 in legal fees, defendant was forced to plead guilty to selling unapproved new
drugs. Six months house arrest. $5,000 fine.
Raid: Natures Way - June 30, 1992
Address: 1375 N. Mountain Springs Parkway, Springville, Utah 84663
Reason: The FDA seized a quantity of evening primrose oil, both encapsulated and in bulk, from this large
manufacturer during a routine inspection. They also seized a truckload of primrose oil on the road. The FDA
claimed it was an unapproved food additive.
Outcome: Nature's Way filed a lawsuit to get their product back, but was forced to remove the vitamin E from it
because the FDA said that Vitamin E has not been approved as a food additive for evening primrose oil.

Raid: Solid Gold Pet Foods - Sept., 1989
Address: 1483 N. Cuyamaca, El Cajon, CA 92020
Reason: FDA had been harassing McGill over labels on her holistic pet food products. In March 1990, an FDA
agent seized products from her store without a search warrant and shut down her store. On July 12, 1990, after
being indicted, she chose a jury trial. Upon appearing for her trial, she was clapped into leg irons, put into a
Maximum Security Federal Prison for 179 days, and fined $10,000. While incarcerated she suffered a near fatal
stroke.
Outcome: McGill sued the Department of Justice and won a victory on Feb. 20, 1992. She expects to file a
$25,000,000 lawsuit against the FDA.
Raid: H.A. Lyons mailing Service - Oct. 16, 1990
Address: Driven out of business. Formerly in Phoenix, AZ
Reason: Mailing literature on behalf of vitamin companies with no advance warning. Five armed agents backed by
an armed policeman raided this home-based business run by a young woman.
Outcome: The owner convinced the agents not to seize her checkbook and cash. They did seize all her business
records and literature. No charges were filed.

Raid: Nutricology, Inc. - May 9, 1991
Address: 400 Preda Ave. San Leandro, CA 94577
Reason: FDA raided Nutricology, seized their bank accounts and shut them down for 2 days, charging them
with wire fraud, mail fraud, selling unapproved drugs, unsafe food additives, and misbranded drugs. Twelve
armed agents conducted an exhaustive search of the company's offices and warehouse.
Outcome: On May 23, 1991 Federal Judge D. Lowell Jensen denied the FDA's request for a Preliminary
Injunction. On Sep. 10, 1991, the FDA appealed to the 9th Circuit Court of Appeals but was again denied. On
Sep. 23, 1993, Judge Jensen denied the FDA's motion for summary judgement and granted Nutricology's
motion to eliminate the wire and mail fraud charges.
Raid: Scientific Botanicals - Fall 1991
Address: 8003 Roosevelt Ave. NE 98115
Phone: (206) 527-5521
Reason: Alleged labeling violations. FDA seized herbal extract products and literature sent to physicians. FDA
forced the company to stop using its patented trade names lest they "mislead the consumer."
Outcome: FDA slowly released all seized products, forcing the company to comply with all demands under
threat of being shut down. Company refuses to talk about their case for fear of reprisal.

Raid: Ye Seekers - June 1992
Address: 1221 Blalock, Houston, TX 77055
Reason: In Feb. 1992, Texas health authorities acting under the direction of the FDA seized 50 products from
several health food stores in Texas including Ye Seekers. In June 1992, they seized more than 250 products
including aloe vera, zinc, flax seed oil, herb teas, vitamin C and coenzyme Q-10.
Outcome: Although more than 410 products were seized, the stores haven't filed suit for fear of reprisals.
Raid: Kirwin Whitnah - May 12, 1993
Address: Driven out of business. Formerly in Middletown, CA
Reason: Whitnah was promoting the sale of deprenyl. The FDA considered this "selling an unapproved drug."
His house raided at gun point when he wasn't home, terrorizing a woman staying at the house. They found no
deprenyl. They seized his computer, business records, mailing list, literature, and $4,500 in money orders.
Outcome: No charges were filed, but Whitnah was driven out of business.

Raid: International Nutrition Inc - Jun 24 1993 and Aug. 3, 1993
Address: PO Box 1644 Santa Theresa, NM 88008
Reason: FDA seized $1,000,000 worth of vitamin raw materials and products formulated by Dr. Hans Nieper of
Germany. Also seized were computers and business records.
Outcome: International Nutrition Inc owner agreed to shut down entire business in exchange for no criminal
prosecution.
Raid: Zerbo's Health Food Store - May 1993
Address: 34164 Plymouth Rd., Livonia, MI 48150
Reason: Alleged distribution by 78-year-old Mr. Zerbo of GH-3 to special customers. Armed U.S. Marshalls and
FDA agents cleaned off shelves of coenzyme Q-10, selenium, carnitine, and GH-3. Mr. Zerbo and his daughter
Claire, who manages the store, were indicted on charges of "illegal drug trafficking.“
Outcome: Claire Zerbo wanted to fight her indictment, but chose not to do so because the FDA threatened her
aging, 78-year-old father who has Parkinson's Disease with 7 years in prison. Because of her fear that her father
would die in prison, they both pleaded guilty. Claire will likely receive 3 months probation. Her father is unlikely to
go to prison for more than 4 months.

Raid: Thorne Research - Dec. 12, 1991
Address: 901 Triangle Dr. Sand Point, Idaho 83864
Reason: FDA claimed that vitamin products sold by company were "unapproved drugs." FDA agent and three U.S.
Marshalls seized the company's entire stock of $20,000 worth of products and 11,000 pieces of literature intended
for physicians.
Outcome: Thorne initially notified District Court that it would fight but gave up as the expiration date on the seized
products was approaching and it became too expensive to continue.
Raid: Tahoma Clinic, Dr. Jonathan Wright - May 6, 1992
Address: 24030 132nd Ave. S.E., Kent, WA 98042
Reason: FDA stormed into Wright's clinic with armed sheriffs terrorizing employees and seizing vitamins and other
natural therapies, allergy screening equipment, computers, bank records, and medical records.
Outcome: In Oct. 1992, Wright filed suit in district court charging unlawful search and seizure and demanded his
property back. In response, the FDA convened a Federal Grand Jury and subpoenaed Wright's clinic records.

FDA Advocates that HIV
Patients Use Dietary Supplements
“There is widespread agreement that nutrition
intervention should begin as soon as a diagnosis is
made. Once people realize they are HIV positive,
they should take steps to improve nutrition…
Healthful eating principles, including
importance of certain nutrients and use
of vitamin and mineral supplements.”

April 2015
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4382132/
Meta-Analysis Shows Dietary Supplements Slow HIV Progression
“…micronutrient supplementation substantially and significantly reduces the
risk of HIV disease progression by 38% in adults not on anti-viral therapy.”
“adding the mineral selenium improved the outcome
significantly” (disease progression reduced by 64%).
“addition of zinc to a micronutrient supplement reduced mortality (by 71%)”
“The annual cost per patient of micronutrient supplement
reported ranged from about $12 to $40/year.”

Harsh Penalty for
Challenging
Government Authority

FDA indicted me in November 1991
Sought prison term of >80 Years

Dr. Robert Hayling
Florida civil rights leader
 Jailed for 6 months for asking to be served at a Woolworth's lunch counter.
 Offered plea deals in exchange for promise of no future protests.
 Released after appeals by Martin Luther King, Jackie Robinson, others
http://bigstory.ap.org/article/caec64fd3f9e4731bb9c4bdd801c0879/dr-robert-hayling-florida-civil-rights-leader-dies-86
In 1964 Dr. Hayling imprisoned for defying authority:

Lots of Free Publicity Courtesy of FDA Trying to incarcerate Bill Faloon

Life Extension recommended
metformin 28 years ago…
the FDA went berserk!
March 1995

Type II diabetics taking metformin:
United Kingdom Diabetes Study
►32% reduced risk of diabetic complications
►42% reduced risk for diabetes-related death
►36% reduced all-cause mortality risk
Study results published January 1995
British Medical Journal; Jan 14, 1995;” United Kingdom Prospective Diabetes Study (UKPDS)

Lethal Delays in Approving Ribavirin
1972- Anti-viral effects of ribavirin discovered by ICN Pharma
1983- LifeExtension® recommends ribavirin to its members
1991- FDA brings criminal charges against LifeExtension® founders
1995- FDA brings criminal charges against ICN Pharm founder
1998- FDA approves ribavirin as lifesaving anti-viral therapy
Tragic Outcome:
60,000 hepatitis C victims die waiting
for ribavirin to be approved.
https://www.lifeextension.com/magazine/1998/9/wws

Dietary Supplement Health and Education Act of 1994
Sen. Orrin Hatch (R-Utah) Sen. Tom Harkin (D-Iowa)
These two Senators Saved Our Supplements:
(Prevented FDA from banning/censoring dietary supplements)
+

FDA Surrenders in 1996
This was the first time the FDA has been
forced to give up on a criminal prosecution.
https://www.lifeextension.com/magazine/1996/9/freedom
By February 1996, Federal Judge Daniel
Hurley dismissed all 56 criminal charges
against Saul Kent and William Faloon.
This victory goes beyond winning in court.
The FDA's defeat is a victory for everyone
who cherishes freedom in healthcare.

FDA Surrenders in 1996
https://www.lifeextension.com/magazine/1996/9/freedom

• Forced FDA to allow health claims
on dietary supplements.
• Forced FDA to accelerate approval of
life saving drugs.
• Stopped FDA from censoring off-label
drug information.
Life Extension Victories Against
FDA in Courts & Congress

 Life Extension was funding 18 research
projects aimed at slowing aging in 1987.
 On February 26, 1987, FDA raided Life
Extension and seized 4,000 copies of
newsletter describing the research.
 Four years later FDA ordered by a
Federal Judge to return seized
newsletters, dietary supplements, and
pay Life Extension’s attorneys fees.
 All anti-aging research torpedoed
because of FDA’s actions.
FDA Destroys Anti-Aging Research in 1987

 England approves metformin:1957
 FDA approves metformin: 1994
 37-year delay caused millions of
American deaths.
 66 years later most people don’t
know metformin is anti-aging drug.
Regulatory Barriers Must be Abolished!
Deadly Delays…Urgent Need for Reform

Study Results Found on March 21st 2017
Journal of the American Medical Association
JAMA. Published online March 21, 2017. doi:10.1001/jama.2016.17844
Metformin studied in pre-diabetic patients. Compared
to placebo 850 mg of metformin two times a day:
Reduced type II diabetes risk 31%
In patients under age 60: metformin reduced diabetic risk by 58%.
“Metformin can cause weight loss…”
Quote:

Catastrophic Loss of Life
A 2019 study tabulated reductions in cardiovascular mortality in
type II diabetics using metformin.1
Life Extension® calculated how many cardiovascular deaths may
have occurred in response to metformin’s 37-year delay.
This exceeds the death toll of all wars America has ever fought.
1. Association of Treatment With Metformin vs Sulfonylurea With Major Adverse Cardiovascular
Events Among Patients With Diabetes and Reduced Kidney Function. JAMA. 2019 September 19:1-11.
Almost 4 million American diabetics may have died because of
the delay in this one drug (metformin) becoming available.

Decades of
research reveal
demonstrate
disease-fighting
impact of
metformin.

Sept. 2017
Metformin Demonstrates Therapeutic
Effects Against Colon Cancer
Am J Med Sci. 2017 Sep;354(3):246-251. doi: 10.1016/j.amjms.2017.05.006. Epub 2017 May 19.
Metformin Has Positive Therapeutic Effects in Colon Cancer and Lung Cancer.
Colon Cancer Metformin Patients Non-Metformin Patients
Recurrences 4% 19%
Metastases 23% 46%
5-Year Survival 57% 37%
Deaths 48% 76%
(Metformin boosts AMPK activity and indirectly inhibits mTOR)
Conclusion: “Metformin therapy is associated with significantly better prognosis in patients with colon cancer”
Caveat: Some diabetics in control group treated with insulin or sulfonylurea drugs that promote tumor cell propagation.
Diabetics on metformin showed these benefits compared to diabetics not prescribed metformin:

Diabetics taking metformin
have lower cancer rates
Metformin Prevents Cancer
MD Anderson Cancer Center
found risk of pancreatic
cancer was 62% lower in
diabetics using metformin.
Li D, Yeung SC, Hassan MM, Konopleva M, Abbruzzese JL. Antidiabetic therapies
affect risk of pancreatic cancer. Gastroenterology. 2009 Aug;137(2):482-8.

https://www.webmd.com/healthy-aging/story/is-there-a-cure-for-aging
February 20, 2021
“If the results are what
they think they will be, the
whole world could go on
metformin and extend life
for everybody.”
- Nir Barzilai, lead researcher on
“Targeting Aging with Metformin”
Clinical Trial

Metformin Clinical Trial Announced in 2015.
As of ____2023:
No known recruiting
for metformin anti-
aging clinical trial.
The study is not listed on ClinicalTrials.gov. The Federal
regulations demand that any FDA study conducted within
the U.S. must be registered on Clinical Trials.gov prior to
commencing-____ 2023.

Risk of Delaying Clinical Trials
Chronic Diseases May Preclude Systemic Regeneration

https://www.science.org/content/article/fda-s-own-documents-reveal-agency-s-lax-slow-and-secretive-oversight-clinical-research
FDA Clinical Trial Malfeasance Exposed Oct 1, 2020

https://www.science.org/content/article/fda-and-nih-let-clinical-trial-sponsors-keep-results-secret-and-break-law
January 13, 2020

https://www.bmj.com/content/379/bmj.o2628
“The FDA is “endangering public health” by not being candid about
violations that are uncovered during clinical trial site inspections”
“The lack of full transparency and data sharing does not allow
physicians and other medical scientists to confirm the data
independently and make comprehensive risk-benefit assessments…”
“The FDA has a long history of failing adequately to oversee clinical trial sites.
A report in 2007 by the Department of Health and Human Services’ Office of
the Inspector General found the FDA audited less than 1% of the nation’s
clinical trial sites between 2000 and 2005 and was highly critical of the agency
because it did not have a database of operational clinical trial sites.”
BritishMedicalJournalcitesHistoricFDAFailures
November 16, 2022
BritishMedicalJournal

Spring/Summer 1985
“Scientists have shown aging process
can be safely and effectively
“Ironic (FDA) effect…”
“This perturbation of the regulatory process will not be
corrected until the agencies are relieved of the necessity
of making judgments they are not equipped to make.”
“The ironic effect is that consumers are denied access to drugs
that could benefit them on alleged grounds of public health.”
https://www.cato.org/sites/cato.org/files/serials/files/cato-journal/1985/5/cj5n1-10.pdf

Experimental Human Age Reversal Interventions
Urgent Need to Rapidly Accelerate Clinical Trials

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Petition FDA-Congress to
Amend Clinical Trial Constraints
age-reversal.net/FDA

Life Extension front-1977
Long Life Magazine - 1978
 Life Extension® incorporated in
Pompano Beach, Florida in 1977.
 Life Extension® did not attract
first supporter until 1980.
 World’s largest anti-aging group…
500,000 supporters (2023).

1980-1986: Anti-Aging News
1986-1994: Life Extension Report
1994-2023:Life Extension Magazine
43 Consecutive Years
of Monthly Publication
(> 400,000 copies mailed each month)

1906-2023 = 117 Years of Needless Deaths

March 2002
Life Extension Magazine-March 2002

Marriott Hotel
West Palm Beach, FL
What’s Delaying
Regenerative Medicine?
William Faloon
February 9th 2023

Regulatory Tyranny:
FDA versus Humanity
William Faloon
Marriott Hotel
West Palm Beach, Florida
February 9th 2023

Bill Faloon on what's delaying regenerative medicine in 2023.pptx

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