>> GOOD MORNING.
I'M DR. SHILPY DIXIT WITH THE
NATIONAL HEART, LUNG AND BLOOD
INSTITUTE AT THE NIH.
ON BEHALF OF THE NHLBI OBESITY
WORKING GROUP I'M EXCITED TO
SERVE AS MODERATOR FOR THE
12th OBESITY, NUTRITION AND
PHYSICAL ACTIVITY SEMINAR.
PAST PRESENTATIONS HIGHLIGHTED A
VARIETY OF TOPICS SUCH AS
TECHNOLOGY ASSISTED INTERVENTION
FOR WEIGHT MANAGEMENT, FOOD
INSECURITY AND COVID-19, ROLE OF
TEACHING KITCHENS IN ADDRESSING
NUTRITION DISPARITIES, AND MANY
OTHERS.
TODAY'S PRESENTATION IS ENTITLED
INTERMITTENT FASTING AND
CIRCADIAN CLOCK, DOES WHEN YOU
EAT AFFECT YOUR HEALTH?
BEFORE WE START, I WANT TO
REVIEW A FEW HOUSEKEEPING ITEMS.
THROUGHOUT THE PRESENTATION AND
DURING THE MODERATED Q&A, PLEASE
SEND ANY QUESTIONS TO THE E-MAIL
ADDRESS LISTED ON THE SLIDES,
ONPA@MAIL.NIH.GOV, OR CLICK THE
LIVE FEEDBACK AT THE BOTTOM OF
THE VIDEOCAST SCREEN TO SUBMIT A
QUESTION OR COMMENT.
THE INFORMATION PRESENTED IN
THIS SEMINAR IS MEANT TO
HIGHLIGHT RESEARCH THAT SUPPORTS
THIS TYPE OF INTERVENTION.
PLEASE SPEAK TO YOUR HEALTH CARE
PROFESSIONAL BEFORE BEGINNING
DIETARY INTERVENTION, ESPECIALLY
IF HYPOGLYCEMIA IS A CONCERN AS
WITH DIABETES.
TO BEGIN, LET ME INTRODUCE OUR
SPEAKER.
DR. COURTNEY PETERSON IS
ASSOCIATE PROFESSOR NUTRITION
SCIENCE UNIVERSITY OF ALABAMA
BIRMINGHAM, CONDUCTED THE FIRST
CONTROLLED FEEDING TRIAL OF
INTERMITTENT FASTING IN HUMANS
AND FIRST TO TEST EARLY TIME
RESTRICTED EATING IN HUMANS.
CURRENTLY IS LEAD INVESTIGATOR
OF ACCEPT CLINICAL TRIALS ON
TIME RESTRICTED EATING INCLUDING
TWO OF THE LARGEST.
HER RESEARCH IS FEATURED IN MORE
THAN 50 MEDIA OUTLETS INCLUDING
NBC NIGHTLY NEWS, "NEW YORK
TIMES," WASHINGTON POST, WALL
STREET JOURNAL, GOOD MORNING
AMERICA, AND THE BBC.
WE'RE THRILLED TO HAVE HER
PRESENT TODAY ON THIS
INTERESTING TOPIC.
WELCOME, DR. PETERSON.
>> THANK YOU FOR HAVING ME.
I'M GOING TO TALK ABOUT WHAT WE
KNOW ABOUT INTERMITTENT FASTING
AND CIRCADIAN CLOCK AND TRY TO
ANSWER THE QUESTION, DOES WHEN
YOU EAT AFFECT YOUR HEALTH.
BACK GROUND, MY TRAINING, MY
ORIGINAL TRAINING WAS
ACTUALLY -- I RECEIVED A Ph.D.
IN THEORETICAL PHYSICS AND
SWITCHED FIELDS TO STUDY
NUTRITION AND METABOLISM.
I'LL START THE FIRST HALF OF THE
TALK TELLING THE STORY OF THE
FIELD OF INTERMITTENT FASTING
FROM A METABOLIC ANGLE AND
TRANSITION TALKING ABOUT IT MORE
FROM A BIOLOGICAL ANGLE, TO
PRESENT NEW CONTENT THAT YOU
HAVEN'T SEEN BEFORE.
I HAVE NO DISCLOSURES.
ARE LET'S START AT GROUND ZERO.
SO, INTERMITTENT FASTING IS ANY
SORT OF MEAL TIMING INTERVENTION
OR APPROACH THAT ALTERNATES
PERIODS OF EATING AND EXTENDED
FASTING.
HISTORICALLY THERE'S NO ONE
SINGLE DEFINITION THAT EVERYONE
AGREED TO A MINIMUM NUMBER OF
HOURS FOR SOMETHING TO
CONSTITUTE INTERMITTENT FASTING.
I SERVE ON INTERNATIONAL
CONSENSUS COMMITTEE TRYING TO
HARMONIZE DEFINITIONS OF
INTERMITTENT FASTING, CONVERGING
TOWARDS A 14-HOUR OR LONGER
DEFINITION IN THE HUMAN SPECIES.
I LIKE THIS DEFINITION FOR TWO
REASONS.
ONE, IF YOU LOOK AT DATA FROM
NHANES, ONE OF THE LARGEST
ASSESSMENTS IN THE U.S., IF YOU
LOOK AT THE MEDIAN FASTING AND
EATING DURATION EACH DAY, THE
MEDIAN AMERICAN IS CURRENTLY
EATING OVER A 12-HOUR PERIOD
EACH DAY.
SO FASTING FOR 12 HOURS A DAY.
SECOND, IF YOU LOOK AT DATA ON
SUBSTRATE OXIDATION AS A
FUNCTION OF THE NUMBER OF HOURS
SOMEONE'S BEEN FASTING, WE
REALLY DON'T SEE A BIG
UPREGULATION IN FATTY ACID
OXIDASE OR GLUCONEOGENESIS UNTIL
14 TO 20 HOURS OF FASTING.
SO I THINK THE 14-HOUR
DEFINITION IN THE HUMAN SPECIES
IS A VERY GOOD ONE.
I'LL USE THIS DEFINITION
THROUGHOUT MY TALK TODAY.
THE FIRST RESEARCH WE HAD ON
INTERMITTENT FASTING DATES BACK
TO THE 1940s, FIRST DATA THAT
ENTER MITT -- INTERMITTENT
FASTING EXTENDS THE LIFESPAN,
UNTIL THE MODERN SEMINAR STUDY
ON INTERMITTENT FASTING, WITH AN
ENTERTAINING BACK STORY.
BACK AROUND THE TURN OF THE
CENTURY, MARK MATTSON, ONE OF
THE LARGEST RESEARCHERS IN THE
FIELD OF INTERMITTENT FASTING,
AND HIS POSTDOC WERE HAVING A
DEBATE ON WHETHER THE BENEFICIAL
EFFECTS OF CALORIE RESTRICTION
WERE DUE TO THE REDUCTION IN
CALORIES OR WHETHER IT WAS DUE
TO THE EXTENSION OF THE DAILY
FASTING PERIOD.
A LOT OF MOVED ALSO OF CALORIE
RESTRICTION, RODENT MODELS,
RODENTS EAT IN A SHORTER TIME
PERIOD SO A LONGER FASTING
PERIOD.
TO RESOLVE, THEY CONDUCTED THE
FOLLOWING STUDY.
IN THIS STUDY THEY TOOK RODENTS,
FIRST GROUP CONTROL GROUP,
SECOND WAS CALORIE RESTRICTED,
ATE 35% LESS THAN CALORIE NEEDS,
THE THIRD GROUP PRACTICED
INTERMITTENT FASTING BY DOING
ALTERNATE-DAY FASTING WHERE
EVERY OTHER DAY THEY HAD A
COMPLETE 24-HOUR WATER ONLY
FAST.
THE FOURTH WAS PAIR FED, GIVEN
AS MUCH FOOD BUT CUT CALORIES
THE SAME AMOUNT EVERY DAY.
WHAT THEY FOUND IN THE STUDY
THAT WAS SO REMARKABLE IS THE
INTERMITTENT FASTING GROUP HAD
LOWER GLUCOSE LEVEL, NEURONS
BETTER ABLE TO WITHSTAND
CYTOTOXIC INJURY.
EVEN RELATIVE TO THE PAIR-FED
GROUP THAT EIGHTH THE SAME
NUMBER OF CALORIES.
THIS WAS SOME OF THE FIRST
EVIDENCE THAT IT HAS BENEFITS
INDEPENDENT OF CALORIE
RESTRICTION.
THERE'S BEEN A HUGE FLURRY OF
RESEARCH, SOME FROM THE
METABOLIC AND AGING COMMUNITIES,
OTHERS FROM CHRONOBIOLOGY.
WHAT'S REMARKABLE IS CONSENSUS
IN ANIMAL MODELS IS QUITE GOOD,
WITH A WIDE RANGE OF BENEFITS.
THERE ARE A LOT OF VERY
DIFFERENT SORT OF EFFECTS IN THE
BODY.
THESE INCLUDE THINGS LIKE WEIGHT
LOSS, REDUCTION IN INSULIN LEVEL
RESPECT, AND/OR IGF1 SIGNALING,
INCREASES IN METABOLIC
FLEXIBILITY, THE ABILITY TO
SWITCH BETWEEN BURNING
CARBOHYDRATES VERSUS FAT FOR
FUEL.
INCREASES IN AUTOPHAGY, CHANGES
OR ALTERATIONS IN
NUTRIENT-SENSING PATHWAYS
USUALLY ASSOCIATED WITH
INCREASED LONGEVITY SUCH AS
mTOR, INCREASES IN ANTIOXIDANT
CAPACITY, REDUCTION IN REACTIVE
OXYGEN SPECIES PRODUCTION,
IMPROVEMENT IN MITOCHONDRIAL
FUNCTION, ALTERATIONS IN
NEUROTROPHIC FACTORS SUCH AS
BBNF, HORMESIS AND STRESS
RESISTANCE, FASTING NATRIURESIS,
THERE'S DATA SUGGESTING
PROLONGED FASTING ACTUALLY
ALLOWS THE BODY TO EXCRETE MORE
SODIUM WHICH IN TURN LOWERS
BLOOD PRESSURE.
AND SOME FORMS OF INTERMITTENT
FASTING THOUGH NOT ALL
APPRECIABLY INCREASE KETONE
LEVELS, AND MORE RECENTLY WE
FOUND INTERMITTENT FASTING SEEMS
TO BE QUITE IMPORTANT ON A
MOLECULAR LEVEL FOR MAINTAINING
A STRONG CIRCADIAN RHYTHM.
I HAVE THE INCREDIBLE CHALLENGE
OF SUMMARIZING A HUGE BODY OF
RESEARCH, I COULD CITE 200
STUDIES BUT I ONLY HAVE 40
MINUTES, I'LL DO MY BEST TO GIVE
YOU A TOUR OF THE LITERATURE BT
ASK ME QUESTIONS ON ANYTHING AT
THE END OF THE TALK.
BEFORE WE MOVE TO HUMAN RESEARCH
I WANT TO MENTION WE HAVE THREE
REALLY IMPORTANT SEMINAL STUDIES
ON INTERMITTENT FASTING AND
LIFESPAN IN THE LAST FIVE YEARS.
THOSE REFERENCES ARE PROVIDED AT
THE BOTTOM.
THE FIRST OF THESE WAS A STUDY
OUT OF A LAB IN 2018, ABLE TO
SHOW AT LEAST 40% OF THE
LIFE-EXTENDING BENEFITS OF
CALORIE RESTRICTION ARE IN FACT
NOT DUE TO REDUCTION IN CALORIES
BUT INSTEAD DUE TO INCREASE IN
DAILY FASTING PERIOD.
SO, A LOT OF THE -- AT LEAST A
FAIR A BENEFIT WE THOUGHT WERE
DUE TO CALORIE RESTRICTION WERE
DUE TO INTERMITTENT FASTING.
A STUDY PUBLISHED LAST YEAR IN
"SCIENCE," DONE IN RODENTS,
TRYING TO FIGURE OUT -- TEASING
APART EFFECTS OF CALORIE
RESTRICTION VERSUS INTERMITTENT
FASTING ON LIFESPAN.
IN THIS PARTICULAR STUDY THEY
ENED UP FINDING INTERMITTENT
FASTING INCREASED MORE THAN
CALORIE RESTRICTION.
THEY RANDOMIZED RODENTS TO 1 OF
6 GROUPS, ONE IN GRAY, THE
SECOND JUST DID CALORIE
RESTRICTION, SHOWN IN PURPLE.
THE THIRD AND FOURTH GROUPS WERE
GROUPS THAT DID THE SAME CALORIE
RESTRICTION BUT RESTRICTED THEIR
FOOD INTAKE DURING THE
BIOLOGICAL NIGHT SO LISTED AS
THE DAY BUT DURING THE NORMAL
PERIOD THAT RODENTS SHOULD BE
SLEEPING.
AND THE FOURTH PAIR OF GROUPS
DID CALORIE RESTRICTION BUT THEY
ATE DURING THE NORMAL FEEDING
TIME.
THE REALLY INTERESTING THING IS
RELATIVE TO THE CONTROL GROUP,
CALORIE RESTRICTION INCREASED
LIFESPAN BY 10%.
BUT IF YOU ADDITIONALLY ADDED A
LONGER FASTING PERIOD AT THE
WRONG TIME OF THE DAY, YOU GOT A
20% INCREASE IN LIFESPAN.
BUT IF YOU ALSO MOVE THAT
FASTING PERIOD TO THE RIGHT TIME
OF DAY, SO MEANING AT NIGHT, YOU
GOT A 35% INCREASE IN LIFESPAN.
THE NET PUNCHLINE IS PROLONGED
DAILY FASTING WAS MORE EHE CAN
IFIVE FOR INCREASING LIFESPAN
THAN C.R.
AND WHAT WAS REALLY IMPORTANT
ABOUT THIS STUDY PUBLISHED IN
"SCIENCE," EFFECTS WERE
INDEPENDENT OF BODY WEIGHT,
MEANING THERE WAS NO EVIDENCE OF
IMPROVEMENT IN CARDIOMETABOLIC
HEALTH BUT WE STILL HAD PROFOUND
EFFECTS ON LIFESPAN EXTENSION.
THIS LAST STUDY DONE IN FRUIT
FLIES ESTABLISHED THAT THE MAIN
MECHANISM FOR LIFESPAN EXTENSION
WAS INCREASED IN AUTOPHAGY AT
NIGHTTIME AND DEMONSTRATED WITH
BOTH OVEREXPRESSION MODELS AS
WELL AS KNOCKDOWN MODELS OF
AUTOPHAGY GENES.
THE BIG PICTURE QUESTION IS DO
THESE RESULTS TRANSLATE FROM
ANIMALS INTO HUMANS?
THERE'S SEVERAL REASONS FOR US
TO THINK THE TRANSLATION RESULTS
MAY NOT BE AUTOMATIC SO FOR
INSTANCE, RODENTS ARE NOCTURNAL,
THEY HAVE MULTIPLE SLEEP
EPISODES PER DAY, AND FASTING
FOR 12 HOURS IN A RODENT COULD
BE EQUIVALENT TO A COUPLE DAYS
IN HUMANS.
THIS LEADS TO THREE QUESTIONS
THAT WE AS A FIELD NEED TO
ANSWER.
FIRST IS DOES INTERMITTENT
FASTING WORK IN HUMANS?
THIS IS A QUESTION OF EFFICACY.
SECOND, CAN PEOPLE STICK WITH IT
IN THE LONG TERM, HOW
SUSTAINABLE IS IT?
THE THIRD IS ARE THE EFFECTS
SOLELY DUE TO WEIGHT LOSS?
ONE CRITIQUE I OFTEN AREA, ONE
HYPOTHESIS, INTERMITTENT FASTING
IS JUST ANOTHER FANCY WAY TO
LOSE WEIGHT WHICH MAY BE TRUE,
CERTAINLY FOR CERTAIN TYPES OF
INTERMITTENT FASTING BUT THIS
BEGS THE QUESTION OF MECHANISMS,
WHAT ARE THE UNDERLYING
MECHANISMS?
EVEN IF WE DO FIND SEVERAL TIMES
OF INTERMITTENT FASTING ARE NO
BETTER THAN CALORIE RESTRICTION,
I DON'T THINK THAT'S A LOSS
BECAUSE WHAT'S QUITE INTERESTING
IS INTERMITTENT FASTING, YOU
TYPICALLY ARE SUBSTITUTING
COUNTING TIME INSTEAD OF
COUNTING CALORIES SO INSTEAD OF
MAKING PEOPLE COUNT CALORIES
THEY HAVE TO START AND STOP AT A
CERTAIN TIME OF DAY.
THERE IS PRELIMINARY EVIDENCE
SLOWING PEOPLE HAVE HIGHER LEVEL
OF SATISFACTION.
EVEN IF IT'S NO BETTER THAN
STANDARD CALORIE COUNTING THERE
MAY BE BEHAVIORAL ADVANTAGES TO
INTERMITTENT FASTING.
SO THERE'S SEVERAL TIMES OF
INTERMITTENT FASTING, AND I LIKE
TO GROUP THEM IN THREE
CATEGORIES TO MAKE SENSE OF THE
FIELD AS A WHOLE.
FIRST APPROACH, PERIODIC
FASTING, NOT EVERYONE USES THAT
TERM THE SAME WAY.
BUT THESE ARE APPROACHES WHERE
YOU FAST FOR AT LEAST 24 HOURS
AT A TIME, WATER-ONLY FASTING.
SOME NUMBER OF TIMES PER WEEK,
OR PER MONTH.
EXAMPLE WOULD BE WATER-ONLY
FASTING, ONE DAY A WEEK, OR
ALTERNATE-DAY FASTING, EVERY
OTHER DAY YOU HAVE A COMPLETE
WATER-ONLY FAST.
THE SECOND TYPE OF APPROACH IS
MODIFIED FASTING APPROACHES, YOU
MIGHT ALSO CALL THEM YOUR
INTERMITTENT ENERGY RESTRICTION
APPROACHES, IER.
THESE ARE APPROACHES WHERE
INSTEAD OF HAVING A FULL 24-HOUR
WATER ONLY FAST YOU EAT A LOW
CALORIE DIET, YOUR MODIFIED
FAST.
TYPICALLY ON THOSE DAYS YOU'RE
EATING LESS THAN 800 CALORIES OR
EQUIVALENT OF ONE MEAL THAT DAY.
EXAMPLES INCLUDE ALTERNATE DAY
MODIFIED FASTING, EVERY OTHER
DAY YOU EAT TYPICALLY THE
EQUIVALENT OF ONE MEAL A DAY.
THE FIVE-TWO DIET, PICK TWO DAYS
A WEEK TO HAVE MODIFIED FAST.
FASTING MIMICKING DIET, WHERE
YOU PICK THREE TO FIVE DAYS IN A
ROW TO EAT A LOW CALORIE DIET.
REPEAT THAT SOME NUMBER OF TIMES
PER YEAR.
AND INTERMITTENT ENERGY
RESTRICTION, WHERE YOU TYPICALLY
WILL PICK A WEEK TO EAT A VERY
LOW CALORIE DIET, CYCLE THROUGH
PERIODS OF EATING AND ENERGY
BALANCE.
THE LAST CATEGORY ARE YOUR DAILY
INTERMITTENT FASTING APPROACHES
WHICH ARE NOW KNOWN AS
TIME-RESTRICTED EATING IN
HUMANS.
THESE ARE QUITE DIFFERENT FROM
THE OTHER TYPES OF APPROACHES.
THERE'S NOT A SPECIFIC CALORIE
TARGET YOU'RE TRYING TO MEET ON
EITHER YOUR FASTING OR MODIFIED
FASTING DAYS.
INSTEAD, WHAT YOU'RE TRYING TO
DO IS CONDENSE EATING TO A
SHORTER TIME PERIOD, EITHER BY
EATING BREAKFAST LATER AND/OR
DINNER EARLIER.
ONE OF THE FIRST MODERN STUDIES
OF INTERMITTENT FASTING IN
HUMANS WAS THIS STUDY DONE BY MY
POSTDOCTORAL MENTOR PUBLISHED IN
2005.
IN THIS APPROACH, THEY STUDIED
ALTERNATE DAY FASTING, THE MOST
COMMON FORM OF INTERMITTENT
FASTING STUDIED BACK THEN, ADF.
EVERY OTHER DAY WATER-ONLY FAST.
THEY TOOK 16 PEOPLE AND HAD THEM
TRY ALTERNATE-DAY FASTING.
WHAT THEY FOUND IS INDEED
ALTERNATE DAY FASTING INDUCED
WEIGHT LOSS, PEOPLE WEREN'T
COMPENSATING BY OVEREATING ON
NORMAL DAYS.
IF YOU READ DISCUSSION SESSIONS
HUNGER MARKEDLY INCREASED IN
PARTICIPANTS WITH NO SIGNS OF
ADAPTATION OVER TIME OR WITH
HUNGER LESSENING OVER TIME, SO
PARTICIPANTS WERE EXTREMELY
HANGRY IN THE STUDY, NOT
SUSTAINABLE IN HUMANS.
MOST PEOPLE STOPPED STUDYING
ALTERNATE DAY FASTING IN HUMANS.
I'LL SAY TWO RECENT STUDIES
CITED HERE, THE FIRST COMPARISON
OF ALTERNATE DAY FASTING TO
REGULAR CONTINUOUS ENERGY
RESTRICTION, WHICH YOU CAN THINK
OF AS CONVENTIONAL DAILY
DIETING.
AND RESULTS ON WHETHER ALTERNATE
DAY, RESULTS ARE MIXED.
THE SECOND APPROACH WELL STUDIED
IN HUMANS IS ALTERNATE DAY
MODIFIED FASTING, WHERE EVERY
OTHER DAY YOU HAVE -- YOU EAT 25
TO 35% OF YOUR DAILY CALORIC
NEEDS.
THIS APPROACH HAS BEEN MOST
STUDIED, INCLUDING IMPROVEMENT
IN CARDIOMETABOLIC HEALTH,
INCLUDING WEIGHT LOSS,
CHOLESTEROL LEVELS, FASTING
GLUCOSE LEVELS AND BLOOD
PRESSURE.
SHE ENDED UP DOING A LARGE SCALE
STUDY ON ALTERNATE DAY MODIFIED
FASTING.
IN THIS PARTICULAR STUDY
PUBLISHED IN 2017, SHE TOOK 100
PARTICIPANTS WITH OBESITY, AND
FOR ONE YEAR RANDOMIZED EITHER
TO A WEIGHT STABLE CHROME GROUP,
TO CONTINUOUS ENERGY
RESTRICTION, I'M GOING TO START
USING ABBREVIATION CER,
CONVENTIONAL DAILY DIETING
COUNTING CALORIES AND CUTTING
THEM BY THE SAME AMOUNT EVERY
DAY.
AND THEN ALTERNATE DAY MODIFIED
FASTING, WHERE EVERY OTHER DAY
YOU EAT A VERY LOW CALORIE DIET
THE CER AND ADMF GROUPS WERE
COUNSELED TO HAVE THE SAME NET
REDUCTION IN CALORIES OVER A
WEEK ON AVERAGE.
THE INTERESTING THING, THERE
WERE NO DIFFERENCES BETWEEN
CONTINUOUS ENERGY RESTRICTION
AND ALTERNATE DAY MOD NIGHT
FASTING AT ANY TIME POINT DURING
THE STUDY.
MOREOVER, THERE WERE NO
DIFFERENCES IN FASTING
CARDIOMETABOLIC ENDPOINTS,
VISCERAL FAT OR INFLAMMATORY
MARKERS.
TWO ARE EQUIVALENT, BUT THE
DROPOUT RATE WAS HIGHER FOR THE
ALTERNATE DAY MODIFIED GROUP
SUGGESTING ALTERNATE DAY MOD
NIGHT FASTING WAS LESS FEASIBLE
THAN TRADITIONAL CONTINUOUS
ENERGY RESTRICTION.
THERE WAS A COUPLE SILVER
LININGS.
THEY DID A SMALL NUMBER OF POST
HOC ANALYSES.
IN ONE, THEY LOOKED AT THE
EFFECTS ON VARIOUS GLYCEMIC
OUTCOMES IN INDIVIDUALS WITH
INSULIN RESISTANCE AT THE START.
IN THOSE WITH PROBLEMS IN BLOOD
SUGAR AT THE BEGINNING THEY
FOUND GREATER REDUCTION IN LEVEL
WITH ALTERNATE DAY MODIFIED
FASTING AND GREATER IMPROVEMENT
IN INSULIN RESISTANCE.
THERE MAY BE SOME BENEFITS THERE
FOR IMPROVING BLOOD SUGAR
CONTROL.
THIRD TYPE OF APPROACH I WANT TO
MENTION IS 5:2 DIET, A LESS
EXTREME FORM BECAUSE INSTEAD OF
HAVING MODIFIED FAST EVERY OTHER
DAY, YOU PICK TWO DAYS A WEEK TO
HAVE A MODIFIED FAST.
THOSE DAYS WITH BE CONSECUTIVE
OR NON-CONSECUTIVE.
AND MY READING OF LITERATURE
THERE TEND TO BE MORE POSITIVE
RESULTS FOR APPROACHES WHERE
THEY USE CONSECUTIVE -- WHERE
TWO DAYS ARE CONSECUTIVE, BUT
NONETHELESS WHEN I STARTED
GIVING THESE TALKS THERE WERE
ONLY FOUR STUDIES ON THE 5:2
DIET, WE'RE NOW UP TO 25
CLINICAL TRIALS ON THE 5:2 DIET.
THIS APPROACH IS POPULAR IN
EUROPE AND ENGLAND.
THE STUDY THAT PUT THE 5:2 DIET
ON THE MAP WAS THE 2013 TRIAL ,
THREE-MONTH STUDY OF 115 WOMEN
OVERWEIGHT WITH A HISTORY OF
BREAST CANCER, CER COMPARED TO
5:2 DIET, USING CONSECUTIVE
DAYS.
THEY FOUND THE 5:2 DIET WAS MORE
EFFECTIVE AT REDUCING BODY FAT
LEVELS, INSULIN LEVELS AND
INSULIN RESISTANCE THAN
CONTINUOUS ENERGY RESTRICTION,
SOME OF THE FIRST DATA IN HUMANS
INDICATING THAT INTERMITTENT
FASTING MAY BE MORE EFFECTIVE
THAN CONTINUOUS ENERGY
RESTRICTION FOR IMPROVING
CARDIOMETABOLIC HEALTH.
SINCE THEN, WE HAVE FINALLY COME
TO A PLACE WHERE WE HAVE FIVE
ONE-YEAR LONG RANDOMIZED
CONTROLLED TRIALS, IF YOU TRY TO
MAKE SENSE OF THE RESULTS THREE
OF THOSE STUDIES REPORT GREATER
WEIGHT LOSS AT SIX OR TWELVE
WEEKS, OR ALMOST STATISTICALLY
GREATER WEIGHT LOSS AT SIX OR
TWELVE WEEKS.
BUT NONE REPORT SUPERIOR WEIGHT
LOSS OUTCOMES AT THE ONE-YEAR
MARK.
ALL THREE OF THOSE STUDIES THAT
FOUND GREATER SHORT-TERM WEIGHT
LOSS WERE ABLE TO TRACE THE
EVAPORATION OF THOSE BENEFITS AT
THE ONE-YEAR MARK DUE TO
WEIGHTING ADHERENCE, SO IT'S AN
ADHERENCE PROBLEMS WITH THE 5:2
DIET.
OTHER INTERESTING FINDINGS FROM
THESE STUDIES IS ALL OF THESE
STUDIES, PRETTY CONSISTENTLY,
DID NOT FIND IMPROVEMENTS IN
FASTING CARDIOMETABOLIC RISK
FACTORS, BUT ONE AND ONLY THAT
LOOKED AT THE POSTPRANDIAL FOUND
IMPROVEMENT IN C PEPTIDE LEVELS,
INDICATOR OF INSULIN SECRETION
AND TRIGLYCERIDE LEVELS.
WE'RE ONLY SCRATCHING THE
SURFACE AND NEED MORE
POSTPRANDIAL MEASUREMENTS
TENDING TO AFFECT MARKERS AT THE
POSTPRANDIAL LEVEL, LEAVING MORE
ON THE TABLE.
THE FOURTH APPROACH IS
FASTING-MIMICKING DIET, FMD.
THIS IS A LOW-PROTEIN
PLANT-BASED DIET WHERE YOU EAT
700 TO 1100 CALORIES A DAY FOR
THREE TO FIVE DAYS AT A TIME.
YOU REPEAT A NUMBER OF TIMES PER
YEAR, NO MORE OFTEN THAN ONCE A
MONTH.
AND ONE OF THE FIRST LARGE SCALE
STUDIES IN HUMANS WAS THE
THREE-MONTH STUDY IN 100 HEALTHY
ADULTS.
THE CONTROL GROUP WAS
ESSENTIALLY A NO WEIGHT LOSS
CONTROL GROUP.
WHAT THAT FOUND FASTING
MINIMUMMING IMPROVED BROAD BODY
WEIGHT, BODY FAT, IGF1, BLOOD
PRESSURE, NO EFFECT ON GLUCOSE,
LIPIDS.
WE DON'T KNOW HOW IT COMPARES TO
CONTINUOUS ENERGY RESTRICTION
BUT IN THE SHORT TERM FIRST
THREE MONTHS PEOPLE LOSE WEIGHT,
NOT COMPENSATING WHEN THEY GO
OFF THE FASTING MIMICKING DIET.
THE FASTING MINIMUMMINGING DIET
HAS AN INTERESTING BACK STORY,
DEVELOPED BY A DOCTOR WHO HAS
DONE A IMPORTANT WORK ON FASTING
IN CANCER, PARTICULARLY IN
PRE-CLINICAL MODELS.
AND HE WAS INTERESTED IN
APPLYING FASTING IN CANCER
PATIENTS BUT FOUND A LOT OF
TIMES IT WAS HARD TO STICK WITH
THE PROGRAM, ONLY A QUARTER
ACTUALLY WERE WILLING TO TRY
WATER-ONLY FASTING FOR A COUPLE
DAYS AT A TIME.
HE WANTED TO DEVELOP AN
INTERVENTION TO RECAPITULATE A
LOT OF BENEFITS OF FASTING BUT
THAT WOULD BE MORE FEASIBLE TO
DO.
HE DEVELOPED A FASTING MIMICKING
DIET.
AND THE SORT OF THEORY BEHIND
THE FASTING MIMICKING DIET, JUST
FASTING IN GENERAL, IS THAT IT
CAN PROVIDE THE SORT OF DOUBLE
EDGED SWORD TO POTENTIALLY
TARGET OR IMPROVE CANCER
OUTCOMES.
IT'S CALLED THE DIFFERENTIAL
STRESS CESSATION OR RESISTANCE
THEORY, TERMS MEAN SOMETHING
SLIGHTLY DIFFERENT BUT I'LL DO
ENTRY LEVEL DISCUSSION.
THE CORE THEORY IF YOU FAST
NORMAL CELLS DECREASES GLUCOSE
AND NUTRIENTS AND IGF1, AS A
RESULT YOU GET THE CELLS -- THE
CELLS ENTER CELL-PROTECTIVE
MODE, GENERATE LESS OXIDATIVE
STRESS.
APPLY TOXIC INSULT SUCH AS
CHEMOTHERAPY OR RADIATION, SENSE
ARE IN A CELL PROTECTED MODE
SUSTAIN LESS DNA DAMAGE AND DIE
AT LOWER RATE.
CONVERSELY, IF YOU FAST CANCER
CELLS, SAME CONDITIONS, BECAUSE
THEY HAVE ONCOGENIC MUTATIONS
THEY CAN'T ACCESS THESE SAME
CELL PROTECTIVE MECHANISMS, AND
INSTEAD YOU SHIFT THEIR
SUBSTRATE METABOLISM.
YOU CREATE THIS ANTI-WARBURG
LIKE EFFECT AND GET HIGHER
PRODUCTION OF OXIDATIVE STRESS,
IF YOU APPLY CHEMOTHERAPY AND
RADIATION CELLS DIE AT HIGHER
RATE, MORE SELECTIVELY KILLING
CANCER CELLS, MORE SELECTIVELY
PROTECTING NORMAL CELLS AND JUST
STARTING TO SEE SOME FIRST
STUDIES, PRIMARILY ON FASTING
MIMICKING BUT OTHER FORMS OF
INTERMITTENT FASTING BEING
TESTED IN PATIENTS WITH CANCER.
A LOT OF WORK IS BEING DONE IN
ITALY.
HERE IS DATA, NOT A SLAM DUNK
BUT IT IS A STUDY IN 131
PATIENTS WITH HER2-NEGATIVE
STAGE 2 OR STAGE 3 BREAST
CANCER, UNDERPOWERED AND HAD TO
STOP THE TRIAL EARLY BUT
NONETHELESS DID FIND SOME
SUGGESTIVE EVIDENCE THAT THE
FASTING MIMICKING DIET IN THE
INTENTION-TO-TREAT ANALYSIS
IMPROVED RADIOLOGIC
INTERVENTION.
THE FIFTH APPROACH IS
TIME-RESTRICTED EATING,
TIME-RESTRICTED FEEDING, AS IT'S
KNOWN IN ANIMALS.
THESE HAVE MOST RAPIDLY BECOME
POPULAR AMONG THE GENERAL
POPULATION.
IN THESE APPROACH US TYPICALLY
EAT WITHIN A 10-HOUR PERIOD OR
LESS.
AND THE MOST COMMONLY STUDIED
FORM, IN THE LITERATURE, IS
KNOWN AS 16:8 DIET, FAST FOR 16
HOURS A DAY, EAT IN AN 8-HOUR
PERIOD.
WHAT'S SPECIAL ABOUT THESE TYPES
OF APPROACHES RELATIVES TO OTHER
FORMS OF INTERMITTENT FASTING,
THEY ARE FAR MORE CUSTOMIZABLE.
YOU CAN PRACTICE THEM WITH OR
WITHOUT CUTTING CALORIES.
YOU CAN ALSO PRACTICE THEM BY
EATING AT DIFFERENT TIMES OF THE
DAY.
FOR INSTANCE, YOU COULD IN
PRINCIPAL EAT EARLY IN THE DAY,
MOVING DINNER TO SUPER EARLY.
YOU COULD ALSO PRACTICE IT IN
THE MIDDLE OF THE DAY BY
SKIPPING BREAKFAST, OR LATE IN
THE DAY BY SKIPPING BREAKFAST
AND LUNCH.
AND WHAT'S QUITE INTERESTING
ABOUT THE WAY WE'VE STUDIED THIS
SO FAR IS OFTEN WE'VE
IMPLEMENTED INTERVENTIONS
WITHOUT INSTRUCTIONS ON HOW MUCH
TO EAT.
OR WHAT TO EAT.
THESE ARE REALLY RULES OF JUST
TIMENING.
SO IF YOU THINK ABOUT COUNSELING
PATIENTS ON WHAT TO EAT, HOW
MUCH TO EAT, WHEN TO EAT, WE'RE
ONLY LOOKING AT COUNSELING ON
THE WHEN TO EAT SO THE RULES ARE
SIMPLER TO FOLLOW.
THE STUDY THAT'S CREDITED WITH
PUTTING TIME-RESTRICTED EATING
ON THE MAP, THERE ARE OTHER
STUDIES PUBLISHED AROUND THE
SAME TIME, THIS REALLY IMPORTANT
STUDY OUT OF THE SALK INSTITUTE.
THEY COMPARED TIME RESTRICTED
EATING BY EATING OVER AN 8-HOUR
PERIOD VERSUS AD LIBITUM,
SCHEDULES AND HIGH FAT AND
NORMAL CHOW DIET.
ONE REASON IT WAS IMPACTFUL
MATCHED CALORIE INTAKE ACROSS
GROUPS.
TIME RESTRICTED EATING REDUCED
BODY WEIGHT GAIN ON NORMAL AND
HIGH CHOW DIET, IMPROVED GLUCOSE
TOLERANCE ON HIGH FAT, A HOST OF
CARDIOMETABOLIC ENDPOINTS.
THIS IS SOME OF THE FIRST DATA
WE REALLY HAVE SHOWING DAILY
INTERMITTENT FASTING HAS
BENEFITS INDEPENDENT AT LEAST OF
CALORIE INTAKE, EVEN THOUGH
THERE WERE BODY WEIGHT
DIFFERENCES HERE.
AND SINCE THEN THERE HAVE BEEN
MORE THAN 100 ANIMAL STUDIES ON
TIME-RESTRICTED EATING.
THE CONSENSUS IS QUITE GOOD.
I'D SAY IN 75% OR MORE OF THESE
STUDIES, TIME RESTRICTED EATING
REDUCES BODY WEIGHT AND/OR FOOD
INTAKE ESPECIALLY IN RODENT
MODELS OF OBESITY.
IT PREVENTS AND REVERSES TYPE 2
DIABETES, AT LEAST FROM
DIET-INDUCED OBESITY.
IT IMPROVES RANGE OF
CARDIOVASCULAR ENDPOINTS.
SLOWS PROGRESSION OF CANCER AS
WELL AS REDUCES INCIDENCE OF
CANCER.
ALSO SLOWS CERTAIN
NEURODEGENERATIVE CONDITIONS AND
EXTENDS LIFESPAN.
SOME OF THAT DATA FROM ONE OF
THOSE OTHER LIFESPAN STUDIES
THAT I WASN'T ABLE TO SHOW YOU
EARLIER, SHOWING TIME RESTRICTED
EATING EXTENDS LIFESPAN.
ANOTHER IMPORTANT ASPECT THAT
MAKES IT MORE RIPE FOR
TRANSLATION INTO HUMANS OR MORE
PROMISING FROM HEALTH PER
PERSPECTIVES, THE LONGER THE
FASTING PERIOD, THE GREATER THE
BENEFITS BUT THERE DOESN'T SEEM
TO BE A MAGIC THRESHOLD YOU HAVE
TO ACHIEVE PER SE.
IT ALLOWS MORE CUSTOMIZABILITY.
SECOND, TWO RODENT STUDIES FOUND
FOLLOWING TIME RESTRICTED EATING
FIVE DAYS A WEEK, GOING OFF IT
AND PARTYING ON THE WEEKENDS
STILL IMPROVES CARDIOMETABOLIC
HEALTH, NOT TO THE SAME DEGREE
BUT WE DON'T NECESSARILY HAVE TO
FOLLOW THIS SEVEN DAYS A WEEK,
HUMANS DON'T, TO GET SOME SORT
OF BENEFIT.
ONE OF THE FIRST STUDIES WE HAVE
SHOWING THAT TIME RESTRICTED
EATING INDUCED WEIGHT LOSS, THIS
TRIAL HAD PARTICIPANTS EAT OVER
AN 8-HOUR WINDOW FROM 10:00 A.M.
TO 6:00 P.M.
AND THEY DID THIS IN ADULTS WITH
OBESITY AND IMPAIRED TO WEIGHT
STABLE HISTORICAL CONTROLS.
WHAT THEY FOUND IS BY SIMPLY
GIVING PEOPLE TIMING RULES, NOT
WHAT TO EAT OR HOW MUCH, ON
AVERAGE PARTICIPANTS LOST ABOUT
2 1/2% OF THEIR BODY WEIGHT OVER
A 12-WEEK PERIOD.
AND ADHERENCE WAS QUITE GOOD.
SO IT AVERAGED BETWEEN 5 TO 6
DAYS A WEEK, AND WE SEE THIS
CONSISTENTLY ACROSS THE
LITERATURE WITH ONLY A FEW
EXCEPTIONS.
MOST STUDIES REPORTED ADHERENCE
BETWEEN FIVE AND SIX DAYS A
WEEK.
A SLIGHT DECLINE IN ADHERENCE
OVER TIME, MORE FEASIBLE THAN
OTHER FORMS OF INTERMITTENT
FASTING.
TODAY WE'RE UP TO MORE THAN 55
CLINICAL TRIALS ON TIME
RESTRICTED EATING IN HUMANS.
UNFORTUNATELY I WILL SAY MOST OF
THESE STUDIES ARE SMALL, SINGLE
ARM, OR THEY HAVE A WEAK CONTROL
GROUP.
SO QUALITY OF DATA REALLY ISN'T
THERE.
80% OF THE STUDIES FALL INTO
THIS CATEGORY WHERE THERE'S SOME
SORT OF, FOR LACK OF BETTER
WORD, FLAW IN SAMPLE SIZE TOO
SMALL, SINGLE ARM, WEAK CONTROL
GROUP.
WE HAVE FEW STUDIES WITH SAMPLE
SIZES OF MORE THAN 40 PEOPLE PER
GROUP.
THAT'S REALLY NOT ENOUGH
STATISTICAL POWER TO DETECT
IMPORTANT CARDIOMETABOLIC
BENEFITS.
NONETHELESS IF YOU TRY TO MAKE
SENSE OF LITERATURE MANY STUDIES
REPORT BENEFITS.
THESE INCLUDE THINGS LIKE
REDUCTION IN ENERGY INTAKE,
REDUCTIONS IN ADIPOSITY OR BODY
WEIGHT, IMPROVEMENT IN GLYCEMIC
CONTROL OR BLOOD PRESSURE, OR IN
QUALITY OF LIFE.
BUT THERE ARE A LOT OF
CONFLICTING RESULTS AND
PROTOCOLS ARE HIGHLY
HETEROGENEOUS, SOME PROTOCOLS,
FOR INSTANCE, HAVE PEOPLE REDUCE
EATING WINDOW BY ONE TO TWO
HOURS A DAY, OTHERS BY SIX HOURS
A DAY, A LOT OF HETEROGENEITY ON
IMPORTANT ASPECTS OF STUDY
DESIGN.
IF YOU STEP BACK TO MAKE A SENSE
OF ALL THE DATA ON TIME
RESTRICTED EATING AND ASK DOES
IT HELP WITH WEIGHT LOSS, HERE
IS THE ANSWER OR WHERE THE FIELD
IS RIGHT NOW, IN MY OPINION.
SO, A VERY NICE SYSTEMATIC
REVIEW CITED HERE TOOK A LOOK AT
ALL THE STUDIES THAT HAVE BEEN
PUBLISHED, AND FOUND HALF REPORT
A WEIGHT LOSS BENEFIT, AND THE
MEAN EFFECT IS ABOUT 3% OVER 6
TO 8 WEEKS, SO, AGAIN, DURATION
OF STUDY VARIES WIDELY.
THE LAST THREE META-ANALYSES ON
TIME RESTRICTED EATING CONCLUDE
EFFECT, IMPORTANT BECAUSE PRETTY
MUCH UNIVERSALLY ALL INITIAL
META-ANALYSES FOUND NO WEIGHT
LOSS BENEFIT BUT WE'RE GETTING
TO SAMPLE SIZE NOW, WE'RE
WE'RE NOT AT
A THOUSAND, I THINK 900 BASED ON
RECENT MET A ANALYSES, REPORTING
2%.
THEY LOOKED AT RANDOMIZED AND
NON-RANDOMIZED, 2% FOR STUDIES
WITH A GOOD CONTROL GROUP.
WE'RE STARTING TO SEE
META-ANALYSES REPORT BENEFITS IN
OTHER ASPECTS EVER
CARDIOMETABOLIC HEALTH SUCH AS
FASTING GLUCOSE.
MY LAB DID A STUDY, AGAIN
LOOKING AT WEIGHT LOSS IN
RESPONSE TO TIME RESTRICTED
EATING.
WE WERE ABLE TO DO WEIGHT LOSS
MODELING, RATHER THAN RELYING ON
FOOD RECORDS.
THIS WAS A STUDY WE DID IN 90
ADULTS WITH OBESITY.
THEY RANDOMIZED TO 8-HOUR EATING
WINDOW BETWEEN 7:00 A.M. AND
3:00 P.M., THIS IS AN EARLY TIME
RESTRICTED EATING INTERVENTION.
SO PATIENTS MOVED DINNER TO
SUPER EARLY IN THE DAY.
THIS IS A BIT EXTREME BUT JUST
TO DEMONSTRATE THE PRINCIPLE.
VERSUS EATING OVER 12 HOURS OR
LONGER.
WE FOUND THE GROUP THAT DID
EARLY TIME RESTRICTED EATING
LOST MORE WEIGHT AND WHEN WE DID
MODELING OF THESE WEIGHT LOSS
TRAJECTORIES WE FOUND THAT THE
CALORIE DEFICIT WAS EQUIVALENT
TO CUTTING CALORIES BY 214
CALORIES A DAY LOOKING AT ALL
PARTICIPANTS, INCLUDING PEOPLE
WHO DIDN'T STICK WITH THE
PROTOCOL.
EFFECT ROSE TO 350 CALORIES A
DAY IN THOSE WHO AT HEARD FIVE
DAYS A WEEK, EVERY WEEK OF THE
STUDY.
WE ALSO FOUND IMPROVEMENTS IN
MOOD AND DIASTOLIC BLOOD
PRESSURE.
ONE REALLY INTERESTING FINDING
RELATES TO SLEEP.
WE FOUND THAT EARLY TIME
RESTRICTED EATING TO OUR
SURPRISE, MOST OF THE PREVIOUS
LITERATURE WAS NULL, BUT IN THIS
STUDY WE FOUND EARLY TIME
RESTRICTED EATING SHORTENED
SLEEP DURATION BY 30 MINUTES
RELATIVE TO CONTROL GROUP.
FIRST WE THOUGHT THIS IS A
NEGATIVE EFFECT, MAYBE
PARTICIPANTS ARE HUNGRY AT
NIGHT, NOT FALLING ASLEEP, OR
MAYBE THEY HAVE TO GET UP
EARLIER TO PREP MEALS FOR THE
DAY.
BUT WE DIDN'T FIND ANY EVIDENCE
OF EITHER OF THOSE BAILED ON
CORRELATION ANALYSIS.
PARTICIPANTS REPORTED FEELING
MORE ENERGETIC, LESS FATIGUE
DESPITE SLEEPING LESS.
WE'VE PUT OUT HYPOTHESIS,
BECAUSE THERE'S A LONGER TIME TO
REST AND REPAIR, ON A VERY
SIMPLISTIC LEVEL, MAYBE THE NEED
FOR SLEEP IS LESS.
WE'RE FASCINATED BY THIS
QUESTION AND WOULD LOVE TO SEE
MORE STUDIES ON THIS TOPIC.
GOING BACK TO THE MAIN LINE OF
WEIGHT LOSS RESEARCH, WE'VE --
MY LAB HAS BEEN INTERESTED IN
UNDERSTANDING WHAT ARE THE
MECHANISMS UNDERLYING THIS
GREATER WEIGHT LOSS.
WE DID A REALLY NICE STUDY BACK
A FEW YEARS AGO TRYING TO
UNDERSTAND DO INTERMITTENT
FASTING INTERVENTIONS SUCH AS
TIME RESTRICTED EATING INDUCE
WEIGHT LOSS BY DECREASING
APPETITE OR BY INCREASING ENERGY
EXPENDITURE?
WE DID A STUDY IN 11 ADULTS WITH
OVERWEIGHT, AND RANDOMIZED THEM
TO EAT OVER 6-HOUR PERIOD FROM
8:00 A.M. TO 2:00 P.M., OR TO
EAT OVER A 12-HOUR PERIOD, A
CROSSOVER STUDY SO EACH PATIENT
DOES THEIR OWN CONTROL AND TRIED
BOTH EATING SCHEDULES.
AND ON THE FOURTH DAY OF THE
EATING SCHEDULE, WE PUT THEM IN
A RESPIRATORY CHAMBER AND
MEASURED HOW MANY CALORIES THEY
BURNED, WE FOUND NO DIFFERENCES
IN EXPENDITURE SO WE THINK THE
APPROACHES DO NOT SEEM TO
MATERIALLY AFFECT ENERGY
EXPENDITURE OR EFFECTS ARE
SMALL, POWERED TO DETECT
80-CALORIE A DAY DIFFERENCES BUT
DECREASED APPETITES AND WHEN WE
MEASURED SUBJECTIVE HUNGER OVER
THE DAY IT WAS MORE EVEN KEELED
OVER THE DAY, THE OP ISN'T OF
WHAT I WOULD HAVE EXPECTED.
I WOULD HAVE EXPECTED GREATER
SWINGS IN HUNGER BUT WE DIDN'T
SEE THAT.
MOREOVER WHEN WE LOOKED AT
APPETITE HORMONES, OBJECTIVE
MEASURE OF APPETITE, WE FOUND
DECREASES IN ACTIVE GHRELIN
LEVELS IN THE MORNING, INCREASES
IN PYY IN THE EVENING, AND
ALTERATIONS IN LEPTIN LEVELS.
OUTSIDE OF THE TOPIC OF OBESITY
OR ENERGY METABOLISM THERE'S
ALSO DATA SUGGESTING
TIME-RESTRICTED EATING AFFECTS
OTHER ASPECTS OF CARDIOMETABOLIC
HEALTH.
THIS IS FROM THE LARGEST STUDY
IN PATIENTS WITH TYPE 2
DIABETES, 12-WEEK TRIAL, 120
ADULTS OUT OF CHINA.
RANDOMIZED TO EAT OVER 10-HOUR
PERIOD STARTING AT 8:00 A.M.,
ENDING AT 6:00 P.M., OR NO
INSTRUCTIONS ON WHEN TO EAT.
WHAT THEY FOUND IS THAT TIME
RESTRICTED EATING IMPROVED
HEMOGLOBIN A1c, REDUCED
FASTING GLUCOSE AND REDUCED
INSULIN LEVELS, RESISTANCE,
LIPID LEVELS.
WE'RE STARTING TO SEE STUDIES ON
METABOLIC SYNDROME, PREDIABETES,
EVEN SOME CONDITIONS LIKE PCOS
AND M.S.
HERE'S DATA FROM ONE OF THOSE
STUDIES IN ADULTS WITH METABOLIC
SYNDROME.
THIS WAS ONE OF THE FIRST
STUDIES DURN IN PATIENTS WITH
METABOLIC SYNDROME.
AND THEY WERE INSTRUCTED TO
SELECT A 10-HOUR WINDOW DURING
THE DAY TO PRACTICE TIME
RESTRICTED EATING, AND THEY
FOUND TIME RESTRICTED EATING
REDUCED BODY WEIGHT, BODY FAT
WAIST CIRCUMFERENCE.
MY LAB WAS QUITE INTERESTED
SEVERAL YEARS AGO AND DESIGNED
TO DETERMINE TRE CAN IMPROVE
CARDIOMETABOLIC HEALTH.
THE FIRST SCHEDULE WAS 6-HOUR,
STARTING AT 8:00 A.M., ENDING
2:00 P.M.
SECOND WAS EATING OVER A 12-HOUR
PERIOD.
WE HAVE LARGE CHANGES IN FASTING
DURATION.
WE FOUND TIME RESTRICTED EATING
HAS BENEFITS INDEPENDENT OF
WEIGHT LOSS OR FOOD INTAKE
BECAUSE WE MATCHED FOOD INTAKE
ACROSS EATING SCHEDULES SO
PARTICIPANTS WERE FED ENERGY
BALANCE, DIDN'T GAIN OR LOSE
WEIGHT, EVERYTHING WAS PERFECTLY
MATCHED.
WE FOUND THAT INSULIN RESISTANCE
DURING ORAL GLUCOSE TOLERANCE
TEST IMPROVED, AND BETA CELL
RESPONSIVENESS, TO PRODUCE
INSULIN IN RESPONSE TO RISING
GLUCOSE LEVELS, LARGE IMROVMENTS
IN BLOOD PRESSURE, AS WELL AS
MODEST IMPROVEMENTS IN OXIDATIVE
STRESS LEVELS.
WE FOUND NO IMPROVEMENTS IN
LIPID LEVELS SO DON'T THINK OUR
LEADING THEORY RIGHT NOW IS ANY
IMPROVEMENT IN LIPID LEVELS ARE
DRIVEN BY WEIGHT LOSS, NO
IMPROVEMENT IN MAJOR
INFLAMMATORY MARKERS OR HEART
RATE.
SINCE THEN RESULTS HAVE BEEN
REPLICATED BY SEVEN OR
RANDOMIZED CONTROLLED TRIALS,
THERE ARE NOW EIGHT THAT
REPORTED BENEFITS INDEPENDENT OF
CALORIE RESTRICTION, CONSENSUS
IS EXCELLENT IN WELL CAREFULLY
DONE METABOLIC TYPE STUDIES.
HERE IS DATA FROM ANOTHER ONE,
TWO WEEKS TESTING EARLY TIME
RESTRICTED EATING.
THEY FOUND IMPROVEMENT IN OF
GLUCOSE UPTAKE AND BRANCH CHAIN
UPTAKE.
WE FOUND ONLY 4 DAYS OF EARLY
TIME RESTRICTED EATING ACTUALLY
LOWERED 24 HOUR GLUCOSE LEVELS
BY THE SOLID LINE.
WHAT'S SUPER INTERESTING, YOU
CAN SEE VERY BEAUTIFULLY
ILLUSTRATED, IF YOU ONLY
MEASURED FASTING GLUE FASTING U
WOULD MISS CHANGES AT
POSTPRANDIAL LEVELS.
FOOD INTAKE OR CALORIE INTAKE
ARE MATCHED, INSULIN
SENSITIVITY, BLOOD PRESSURE,
BODY FAT.
THERE HAVE BEEN PROMINENT NULL
STUDIES.
HERE IS DATA FROM ONE, PUBLISHED
IN JAMA INTERNAL MEDICINE, THREE
YEARS AGO.
THEY COMPARED TIME-RESTRICTED
EATING BY SKIPPING BREAKFAST,
EATING IN AN 8-HOUR PERIOD
BETWEEN 12 AND 8:00 P.M., VERSUS
THREE MEALS A DAY.
THE ROLE, THEY HAD TO EAT
BREAKFAST.
THEY WEREN'T ALLOWED TO EAT
THREE MEALS LATER IN THE DAY.
THEY FOUND IN 116 ADULTS OVER 12
WEEKS, ABSOLUTELY NO DIFFERENCES
IN BODY WEIGHT BETWEEN THE
GROUPS, MEASURED A VERY LARGE
LIST OF CARDIOMETABOLIC RISK
FACTORS AND COMPOSITION RISK
FACTORS, ALL NULL.
ONE INTERESTING THING,
PARTICIPANTS STARTED GOING TO
BET LATER AT NIGHT.
AT LEAST WITH THIS FORM OF TIME
RESTRICTED EATING THAT MAY BE
AFFECTING SLEEP PATTERNS, DOING
TIME-RESTRICTED EATING BY EATING
LATER IN THE DAY.
THERE'S DATA THAT LATE
TIME-RESTRICTED EATING WHICH
I'LL DEFINE, YOU COULD CALL THIS
MIDDAY OR MIDDLE OF THE DAY
TIME-RESTRICTED EATING BY
SKIPPING BREAKFAST, THIS IS
TIME-RESTRICTED BY SKIPPING
BREAKFAST AND LUNCH.
SO THE LATE RESTRICTED EATING,
DATA IS NULL OR NEGATIVE.
HERE IS FROM ONE, 8-WEEK
CROSSOVER STUDY, THEY COMPARED
TIME-RESTRICTED EATING BEFORE
THE TERM WAS INVENTED BUT
COMPARED EATING IN A 4-HOUR
PERIODS BETWEEN 5 AND 9:00 P.M.
VERSUS THREE MEETS A-- MEALS
ACROSS THE DAY EATING BREAKFAST.
THIS WORSENED POSTPRANDIAL
GLUCOSE LEVELS, EVIDENT AT THE
POSTPRANDIAL LEVEL, THEY FOUND
DELAYED INSULIN SECRETION,
HIGHER BLOOD PRESSURE, WORSE
POSTPRANDIAL LIPID LEVELS.
WE ALL HAVE AN INTERNAL
BIOLOGICAL CLOCK THIS SYSTEM
PRODUCES 24 HOUR RHYTHMS,
METABOLISM, PHYSIOLOGY,
BEHAVIOR.
YOUR GREATEST MUSCULAR STRENGTH
AND BEST COORDINATION ARE IN THE
AFTERNOON.
BODY REALLY STARTS TO PRODUCE
SLEEP HORMONE MELATONIN AT
NIGHT, GREATEST ALERTNESS IS IN
THE MORNING.
ACTUALLY TURNS OUT A NUMBER EVER
METABOLIC RHYTHMS SEEM TO FAVOR
THE MORNING OPTIMAL FOR
METABOLISM.
FOR INSTANCE, IN MOST PEOPLE
WITH EXCEPTION OF SHIFT WORKERS
AND THOSE WITH TYPE 2 DIABETES,
IT APPEARS BLOOD SUGAR CONTROL
IS BEST IN THE MORNING.
WE'VE KNOWN THIS FOR 50 YEARS
NOW, BUT WE DIDN'T KNOW ENOUGH
ABOUT THE CIRCADIAN TO KNOW WHAT
WAS DRIVING THEM.
IF YOU ADMINISTER ORAL GLUCOSE
TOLERANCE TEST IN THE MORNING,
AFTERNOON, EVENING, DESPITE
GIVING PEOPLE THE SAME AMOUNT OF
SUGAR TO CONSUME, LEVELS SPIKE
SIGNIFICANTLY HIGHER IN THE
MORNING AND AFTERNOON, NOT SMALL
EFFECTS, QUITE A HUGE EFFECT, A
40-POINT DIFFERENCE AT THE
TWO-HOUR MARK.
AND IT'S EQUIVALENT TO BASED ON
DEFINITIONS OF PREDIABETES BACK
WHEN TESTS WERE FIRST DEVELOPED,
EQUIVALENT TO BORDERLINE
PRE-DIABETIC IN AFTERNOON.
RHYTHMS SUGGEST MORNING IS
FAVORED, OPTIMAL FOR EATING.
THERMIC EFFECT OF FOOD, HOW MANY
CALORIES YOU BURN WHEN YOU
ABSORB AND DIGEST FOOD IS HIGHER
WHEN YOU EAT IN THE MORNING THAN
AFTERNOON.
MORE STUDIES REPORT INCREASE IN
THERMIC EFFECT OF FOOD IN THE
MORNING.
ALSO WE NOW HAVE THREE VERY
ELEGANT STUDIES DONE IN
METABOLIC CHAMBERS SHOWING WHEN
PEOPLE EAT EARLIER IN THE DAY
THEY ACTUALLY BURN MORE FAT, AND
THAT EXTRA FAT BURNING IS
ACTUALLY AT NIGHT.
WE HAVE NICE DATA REPLICATED
SHOWING GREATER FAT BURNING WITH
EATING EARLIER IN THE DAY.
THERE ARE ALSO SOME RHYTHMS IN
CARDIOVASCULAR ENDPOINTS, LESS
WELL STUDIED.
I SHOULD SAY A LOT LESS WELL
STUDIED IN THE LITERATURE.
FOR INSTANCE WE KNOW THERE'S A
SMALL CIRCADIAN IN BLOOD
PRESSURE, 3 TO 5%, I DON'T
REMEMBER AMPLITUDE.
ALSO WHAT'S QUITE INTERESTING IF
YOU LOOK AT PLASMA METABOLITES
15% HAVE CIRCADIAN RHYTHMS, ALSO
80% ARE LIPID SPECIES.
MOST LIPID SPECIES MID-MORNING
TO NOONTIME BUT UNLIKE GLYCEMIC
CONTROL WITH DISTINCT PHENOTYPES
WHERE THE MAJORITY OF PEOPLE
HAVE OPTIMAL CONTROL IN THE MID
TO LATE MORNINGS, LIPID RHYTHMS
ARE VARIABLE.
SOME APPEAR TO HAVE NO RHYTHM,
TIME OF DAY THEY PEAK IS
VARIABLE, DON'T REALLY
UNDERSTAND THAT YET.
WHEN YOU THINK ABOUT CIRCADIAN
SYSTEM TO UNDERSTAND HOW MEAL
TIMING MIGHT INTERACT WITH THE
CIRCADIAN SYSTEM, WE BREAK DOWN
THE CIRCADIAN SYSTEM IN TWO
PARTS.
ONE IS CENTRAL OR MASTER CLOCK,
LOCATED IN THE SUPER CHIASMATIC
NUCLEUS OF THE HYPER THALAMUS,
TIME ZONE, PHASE IS THE TERM,
ONE IMPORTANT FACTOR IS TIME OF
DAY YOU GET BRIGHT LIGHT
EXPOSURE.
CONVERSELY WE HAVE A NUMBER OF
CLOCKS LOCATED IN EVERY ORGAN
AND TISSUE IN THE BODY,
PERIPHERAL CLOCKS.
AND TIME ZONE IS SET BY FACTORS,
ONE OF THE MOST IMPORTANT
ESPECIALLY FOR HIGHLY METABOLIC
ORGANS SUCH AS LIVER AND
PANCREAS SET BY THE TIME OF DAY
THAT WE EAT.
SAID ANOTHER WAY, SIMPLIFYING
THIS A LITTLE BIT TO A FAULT, TO
GIVE A BIG PICTURE, IF WE HAVE
2:
TWOCLOCK SYSTEMS, IF YOU'RE
EATING OUT OF SYNC WITH BRIGHT
LIGHT EXPOSURE, THEY ARE IN
DIFFERENT TIME ZONES AND GIVE
CONFLICTING SYMBOLS WHETHER TO
REV UP OR REV DOWN, THIS IS ONE
FORM OF WHAT WE CALL CIRCADIAN
MISALIGNMENT, LEADS TO
DYSFUNCTION.
REALLY NICE ANALOGY FOR THIS
CLOCK SYSTEM HERE WHICH HAS BEEN
USED, I DON'T KNOW WHO TO GIVE
CREDIT TO FOR THIS ANALOGY, BUT
THINK OF THE CENTRAL CLOCK OF
CONDUCTOR OF ORCHESTRA, AND EACH
PERIPHERAL CLOCK IS A DIFFERENT
SECTION, IF YOU'RE TRYING TO
PLAY MUSIC, EVERYTHING IS
STARTING THEIR SECTION AT A
DIFFERENT POINT IN THE SCORE AND
SO YOU GET A CACOPHONY.
AND SOME OF THE FIRST REALLY
IMPORTANT DATA SHOWING CIRCADIAN
MISALIGNMENT WORSENS
CARDIOMETABOLIC HEALTH CAME FROM
FOLKS WHO DID THIS IMPORTANT
STUDY IN 2009, SHOWING IF YOU
TAKE HUMANS AND HAVE THEM EAT
ROUGHLY 12 HOURS OUT OF SYNC
WITH WHEN THEY HABITUALLY GET
BRIGHT LIGHT EXPOSURE, THAT THIS
CIRCADIAN MISALIGNMENT INCREASES
24 HOUR GLUCOSE LEVELS BY 6%, 24
HOUR INSULIN LEVELS BY 22%, SO
THIS KEEPS UP WITH THE THEME
BOTH IN INTERMITTENT FASTING AND
CIRCADIAN RESEARCH WHERE WE TEND
TO SEE MORE NEGATIVE CHANGES IN
INSULIN BEFORE WE SEE BIG
CHANGES IN GLUCOSE.
WE ALSO FIND NO WORSENING OF
MEAN ARTERIAL BLOOD PRESSURE, BY
3%, QUITE HUGE DECREASES IN
SLEEP EFFICIENCY BY 20%.
SO THEN YOU MIGHT HEAR THAT DATA
AND SAY GREAT, I WON'T EAT WHEN
IT'S DARK OUTSIDE OR LATER AT
NIGHT.
BUT THERE'S DATA ALSO SUGGESTING
THAT THE TIME OF DAY EVEN DURING
DAYLIGHT HOURS THAT YOU EAT
MATTERS.
IN ISRAEL THEY DID A HALF DOZEN
REALLY IMPORTANT STUDIES ON THIS
CONCEPT EATING BREAKFAST LIKE A
KING, LUNCH LIKE A PRINCE,
DINNER LIKE A PAUPER.
ONE OF THE MOST IMPORTANT FIRST
STUDIES IN 2013 IS THEY TOOK 93
WOMEN OVERWEIGHT, ENROLLED THEM
IN A 12 WEEK LONG TRIAL TO EAT A
LARGE BREAKFAST AND SMALL DINNER
OTHER SMALL BREAKFAST AND LARGE
DINNER.
COUNSELED TO EAT THE SAME NUMBER
OF CALORIES.
A LARGE BREAKFAST LOST MORE
WEIGHT OVER 12 WEEKS, AND THEY
WERE LESS HUNGRY THROUGHOUT THE
DAY.
I LIKE TO LOOK AT THIS FROM THE
FLIP SIDE.
FOR ME IT'S THE GROUP THAT'S
REALLY EATING LATE IN THE DAY
GETTING THE ONE/TWO PUNCH,
STRUGGLING TO LOSE WEIGHT BUT
DESPITE LOSING LESS WEIGHT THEY
ARE MORE HUNGRY THAN THE GROUP
THAT'S MORE SUCCESSFUL AT LOSING
WEIGHT.
THAT'S UNFORTUNATE.
AND THAT GROUP HAS DONE REALLY
IMPORTANT WORK TO SHOW SOME OF
THESE BENEFITS AGAIN ARE
INDEPENDENT OF FOOD OR CALORIE
INTAKE.
THEIR IS DATA FROM A ONE-WEEK
CROSSOVER CONTROLLED FEEDING
STUDY THEY DID.
THEY TRIED THE EXACT SAME ON TWO
EATING SCHEDULES.
AND THEY TOOK 18 ADULTS WITH
TYPE 2 DIABETES, EACH PATIENT
TRIED TWO EATING SCHEDULES.
AGAIN, REALLY FASCINATINGLY THEY
FOUND WHEN THEY MEASURED
GLUCOSE, LOWER LEVELS WITH A
LARGE BREAKFAST AND SMALL
DINNER.
AS WELL AS GREATER INSULIN
SECRETION.
TYPE 2 DIABETES, EXTRA SECRETION
IS A GOOD THING.
AFTER A SINGLE WEEK OF CHANGING
MEAL TIMES THEY WERE ABLE TO
IMPROVE INSULIN SECRETION,
ROUGHLY 15 TO 20% INCREASE AFTER
ONE WEEK OF CHANGING THE TIMING
OF MEALS, QUITE MATERIAL.
AND WE'RE STARTING TO SEE NOW
STUDIES ANSWERING THE QUESTION
OF WHETHER EARLY TIME RESTRICTED
EATING MAY BE MORE EFFICACIOUS,
SO WHETHER IT HAS -- IF YOU
STICK WITH THE PROGRAM
PERFECTLY, WHETHER IT HAS MORE
BENEFITS THAN TIME RESTRICTED
EATING BY SKIPPING BREAKFAST AND
EATING IN THE MIDDLE OF THE DAY.
AFTER SIX OR SEVEN STUDIES ON
THIS NOW, MODERATE SIZE STUDY
GIVES US BETTER CONFIDENCE IN
RESULTS, QUITE INTERESTING ALL
THREE OF THOSE MODERATE SIZE
STUDIES ARE THE ONES WITH LARGER
SAMPLE SIZE DO CONSISTENTLY
REPORT MORE CARDIOMETABOLIC
BENEFITS TO EARLY TIME RESTRICT
THE EATING, THEY JUST REPORT
MORE BENEFITS.
HERE IS A BEAUTIFUL GRAPHIC FROM
ONE WHERE THEY FOUND
STATISTICALLY SIMILAR WEIGHT
LOSS BUT GREATER IMPROVEMENT IN
BLOOD PRESSURE, GLYCEMIC
ENDPOINTS, LEPTIN, HUNGER.
WHERE DOING TIME RESTRICTED
EATING BY SKIPPING BRECK FAST
GOT IMPROVEMENT IN LEPTIN
LEVELS.
INTERMITTENT FASTING IMPROVES
HEALTH AND INCREASES LIFESPAN IN
ANIMALS.
IN OF IN HUMANS INTERVENTIONS
ARE HETEROGENEOUS.
WE NEED TO CONSIDER EACH TYPE
SEPARATELY IN TERMS OF ADHERENCE
AND BIOLOGICAL EFFECT.
ALSO DEMONSTRATED SOME POINT OF
INTERMITTENT FASTING ADHERENCE
IS A MAJOR CHALLENGE.
I DON'T SEE THOSE READILY
TRANSLATING INTO PUBLIC HEALTH
RECOMMENDATIONS SO THAT'S REALLY
IMPORTANT FOR US TO ACKNOWLEDGE.
THE THINK THE DATA IS CLEAR
INTERMITTENT FASTING INDUCES
WEIGHT LOSS AND IMPROVES
CARDIOMETABOLIC HEALTH.
THOUGH I ALSO THINK MOST OF THE
EVIDENCE SUGGESTS THAT FOR AT
LEAST MOST TYPES MAJORITY OF
BENEFITS, I DON'T THINK WE KNOW
ABOUT ALL BENEFITS LIKELY
DERIVED FROM ENERGY RESTRICTION,
THAT'S THE MOST IMPORTANT
MECHANISM AT LEAST FOR MANY OF
THESE TYPES OF INTERMITTENT
FASTING.
FOR TIME RESTRICTED EATING BASED
ON LAST THREE META-ANALYSES WE
CAN SAY TIME RESTRICTED EATING
APPEARS TO REDUCE BODY WEIGHT
MODERATELY COMPARED TO TYPICAL
PATTERNS AROUND TIME RESTRICT
THE EATING CAN HAVE BENEFITS
INDEPENDENT OF WEIGHT LOSS, WE
NEED MORE RESEARCH FOR THE
MULTI-MILLION DOLLAR QUESTION,
HOW MUCH OF THE EFFECTS OF THESE
INTERMITTENT FASTING ARE DUE TO
ENERGY RESTRICTION VERSUS TIME
OF DAY VERSUS EXTENDING FASTING.
WE MIGHT GO IN A DIFFERENT
PUBLIC HEALTH DIRECTION IF TIME
OF DAY IS MORE IMPORTANT.
WE NEED HIGHER QUALITY STUDIES
WITH LARGER SAMPLE SIZES.
WE HAVE MIXED RESULTS IN THE
FIELD.
PART IS BECAUSE LOTS OF PEOPLE
ARE DOING SMALL PILOT STUDIES
BUT WE NEED TO GET TO THE POINT
WE'RE DOING LARGER HIGHER
QUALITY STUDIES.
I'D LIKE TO THANK OUR SPONSORS
AND GRANT SUPPORT, ESPECIALLY
NIH, ALSO DEPARTMENT OF DEFENSE
OVER THE YEARS, AND TO THANK
EVERYONE IN MY LAB WHO MADE
THESE RESULTS POSSIBLE AND OUR
COLLABORATORS.
THANK YOU SO MUCH.
>> THANK YOU SO MUCH, DR.
PETERSON.
JUST SOME QUICK HOUSEKEEPING
NOTES BEFORE WE MOVE TO
QUESTIONS, MORE HOUSEKEEPING
NOTES.
I WANT TO HIGHLIGHT A FEW
RELATED OPPORTUNITIES.
FIRST, THE OFFICE OF NUTRITION
RESEARCH IF WE IS ADVANCE THE
SLIDES TO THIS NOTICE, NEXT
PLEASE.
ONE MORE.
IT MIGHT NOT BE IN THERE.
WELL, THE OFFICE OF NUTRITION
RESEARCH HAS RELEASED AN
INTERAGENCY REQUEST FOR
INFORMATION ON FOOD AS MEDICINE
RESEARCH.
SEARCH THIS NOTICE, NOT-OD-23 -
107, YOU'LL BE ABLE TO FIND THIS
REQUEST FOR INFORMATION AND
OFFER INPUT ON RESEARCH,
OPPORTUNITIES FOR COMMUNITY
ENGAGEMENT, AND OTHER ITEMS THAT
THE OFFICE OF NUTRITION RESEARCH
IS LOOKING FOR.
IF YOU FOUND THIS TOPIC
INTERESTING, AND WOULD LIKE TO
LEARN MORE, PLEASE REGISTER FOR
AN UPCOMING NHLBI ON NUTRITION
ON MAY 2 AND MAY 3 WHERE A
MULTI-DISCIPLINARY GROUP OF
INVESTIGATORS INCLUDING DR.
PETERSON WILL HIGHLIGHT EMERGING
RESEARCH LINKING CIRCADIAN CLOCK
TO NUTRITION-RELATED DISEASE
RISK, PATHOPHYSIOLOGY, AND
INTERVENTION.
YOU CAN REGISTER FOR THIS BY
SEARCHING NHLBI'S PUBLIC WEBSITE
UNDER EVENTS.
I'LL GET TO QUESTIONS NOW
BECAUSE WE HAD AMAZING QUESTIONS
COMING IN FROM OUR AUDIENCE
TODAY.
I'M GOING TO ROLL A FEW INTO
ONE.
THE DATA ON BREAKFAST TIMING AND
SKIPPING BREAKFAST WAS PRETTY
EXCITING.
BOTTOM LINE IS DON'T MISS
BREAKFAST.
BUT IT OPENS UP QUESTIONING TO A
LARGER TIMING-RELATED ISSUE.
SHOULD BREAKFAST -- SHOULD MEALS
IN GENERAL BUT SPECIFICALLY
BREAKFAST GIVEN ITS IMPORTANCE
BASED ON DATA, HAPPEN AT THE
SAME TIME?
WHAT WOULD BE THE OPTIMUM TIME
FOR BREAKFAST MEALS OR DAYTIME
MEALS?
AND SHOULD FASTING OR YOUR
TIME-RESTRICTED EATING TAKE
PLACE AT THE SAME TIME?
SHOULD THE ENERGY BALANCE THERE,
INTAKE BALANCE THERE, OCCUR AT
THE SAME TIMES EVERY DAY?
>> GREAT QUESTION.
I'LL TAKE THE BREAKFAST SKIPPING
QUESTION FIRST.
BREAKFAST SKIPPING QUESTION
TENDS TO BE MUCH MORE NUANCED
THAN IS OBVIOUS.
SO IT'S REALLY INTERESTING,
RESEARCH OUT OF JAPAN PEOPLE
TEND TO SKIP IN TWO WAYS, IN
JAPAN HALF OF PEOPLE SKIP
BREAKFAST AND EAT DINNER AT
NORMAL TIME, PRACTICING
TIME-RESTRICTED EATING
TECHNICALLY.
IF YOU DO THAT BUT SKIP
BREAKFAST DO YOU STILL GET
BENEFITS OF THE PROLONGED DAILY
FASTING PERIOD?
I DON'T THINK WE FULLY KNOW THE
ANSWER YET.
SHORT TERM STUDIES WE HAVE WHERE
PEOPLE SKIP BREAKFAST UP TO A
WEEK, DATA HAS SHOWN THAT AT
LEAST GLUCOSE LEVELS ARE BETTER
WITH EATING THREE MEALS A DAY IF
DINNER IS AT A FIXED TIME THAN
SKIPPING BREAKFAST BUT MAY NOT
GIVE TIME TO TO ADAPT, THERE CD
BE BENEFITS FOR SUSTAINED PERIOD
OF TIME.
THE OTHER HALF OF FOLKS WHO SKIP
BREAKFAST, EAT DINNER LATE, THE
DATA ARE CONSISTENT THAT IF YOU
SKIP BREAKFAST AND EAT DINNER
LATE THERE ARE NEGATIVE
CONSEQUENCES BUT IT'S THE FIRST
BREAKFAST SKIPPING PHENOTYPE
THAT WE HAVE A LOT OF QUESTIONS
ABOUT.
IT'S A QUESTION OF THE TRADEOFF
BETWEEN TIME OF DAY AND
PROLONGED FASTING PERIOD.
SECOND QUESTION, CONSISTENCY, SO
THE RESEARCH WE HAVE IN
PRE-CLINICAL MODELS AND HUMAN
STUDIES REALLY SEEMS TO INDICATE
THAT A CONSISTENT START AND END
TIME IS REALLY IMPORTANT FOR
TIME-RESTRICTED EATING, YOU
CAN'T START AT 8:00 A.M. ONE
DAY, 12:00 P.M. THE NEXT DAY.
IT'S A FORM OF CIRCADIAN
MISALIGNMENT OR SHIFT IS
FREQUENTLY SHIFTING THE TIMING
OF THOSE PERIPHERAL CLOCKS.
AND SO AT LEAST WE BELIEVE
CONSISTENCY OF MEAL TIMES IS
IMPORTANT.
THERE ARE AT LEAST TWO HUMAN
STUDIES THAT DIDN'T COME FROM A
CHRONOBIOLOGY COMMUNITY BUT WITH
VERY CLEVER STUDY DESIGNS SHOWED
WORSE CARDIOMETABOLIC OUTCOMES
WITH IRREGULAR MEAL TIMING.
>> VERY INTERESTING.
GOOD TO KEEP IN MIND.
NEXT QUESTION OR QUESTIONS
ROLLED INTO ONE FOR THE BENEFIT
OF TIME ARE ON DIFFERENT
POPULATIONS WITHIN THE LARGER
POPULATION GROUPS.
SPECIFICALLY, WHEN WE THINK
ABOUT LIFESTYLE INTERVENTIONS OR
BEHAVIORAL INTERVENTIONS TO
BETTER OUR HEALTH OUTCOMES WE
HAVE TO CONSIDER EFFECTIVE AGE
AND THINGS LIKE SHIFT WORK, FOR
EXAMPLE, OR WORK SCHEDULES, LIFE
SCHEDULES, HOW THAT MAY IMPACT
OUR CIRCADIAN RHYTHMS AND MORE
SOCIAL BEHAVIORS, LIKE MEAL
TIMING, RIGHT?
YES, EATING IS BIOLOGICAL.
BUT WE ALSO TEND TO COME
TOGETHER OVER FOOD.
SO, WITH REGARD TO THESE SPECIAL
POPULATIONS, SHIFT WORK
POPULATIONS, EFFECTS OR IMPACTS
ACROSS THE LIFESPAN, WHAT KIND
OF CONSIDERATIONS DO YOU SUGGEST
OR DOES THE DATA INDICATE?
>> YEAH, GREAT QUESTION ABOUT
AGE-RELATED EFFECTS.
I WOULD SAY WE DON'T HAVE ANY
GOOD DATA IN HUMANS WHO THIS
QUESTION.
THERE HAVE BEEN A COUPLE STUDIES
IN OLDER ADULTS, ONE OF THEM I
WAS A CO-INVESTIGATOR ON, WE DID
FIND MODEST IMPROVEMENTS IN
CARDIO RESPIRATORY FITNESS IN
OLDER ADULTS.
BUT THEIR CIRCADIAN RESULTS ARE
DAMPENED OR ATTENUATED, DOES
THAT SUGGEST MORE OR LESS
BENEFITS WITH VARIOUS MEAL TIME
APPROACHES?
NO IDEA.
ANECDOTALLY WE DON'T SEE STRONG
AGE-DEPENDENT EFFECTS, BUT AGAIN
OUR SAMPLE SIZES AREN'T WELL
POWERED TO ANSWER THAT QUESTION.
WE DON'T SEE OBVIOUS EFFECTS FOR
INSTANCE WHERE OLDER ADULTS GET
FEWER BENEFITS BUT WE DON'T HAVE
ANY IDEA.
THERE'S INTERESTING WORK IN
ANIMALS ABOUT AGE OF ONSET OF
INTERMITTENT FASTING AND IN
JUVENILES IT SENDS TO STUNT THE
ANIMALS.
THAT'S A CONCERN.
I DON'T RECOMMEND INTERMITTENT
FASTING IN ADOLESCENCE, THERE'S
SOME STUDIES THAT SHOW YOU NEED
TO INITIATE TIME RESTRICTED
EATING EARLY ENOUGH IN LIFE TO
REALLY GET THOSE BENEFITS.
>> INTERESTING.
OKAY.
ONE OF THE OTHER THINGS THAT
STOOD OUT TO MY, AND ALSO STOOD
OUT TO SOME OTHER PEOPLE, THIS
RELATIONSHIP BETWEEN MEAL TIMING
AND SLEEP.
ALSO TYING INTO THAT THIS THIRD
PILLAR OF HEALTH, PHYSICAL
ACTIVITY.
DIET, PHYSICAL ACTIVITY, AND
SLEEP ARE THESE PILLARS OF
HEALTH.
HOW DO THEY INFORM EACH OTHER
AND WHEN YOU'RE DESIGNING
EXPERIMENTS OR CLINICAL STUDIES,
IS PHYSICAL ACTIVITY TAKEN INTO
ACCOUNT ALONG WITH SLEEP
BEHAVIORS, TO SORT OF SUPPORT OR
REINFORCE, OR WHAT ARE YOU
SEEING IN THE LITERATURE AND
RESEARCH THESE DAYS?
>> GREAT QUESTION.
I'LL TACKLE EACH SEPARATELY.
FOR SLEEP, MOST OF THE STUDIES
ON INTERMITTENT FASTING AND
SLEEP HAVE FOUND ABSOLUTELY NO
EFFECT.
I DON'T WANT TO SAY WE'RE AN
OUTLIER, ANOTHER GROUP HAS BEEN
ABLE TO REPLICATE OUR FINDINGS
BUT HAVEN'T PUBLISHED, SHORTER
SLEEP DURATION BUT GREATER
ENERGY LEVELS, LESS FATIGUE WITH
EARLY TIME RESTRICTED EATING,
EARLY EATING MAY BE KIND OF A
DIFFERENT BEAST.
MOST STUDIES DON'T FIND LARGE
EFFECTS ON SLEEP.
FOR PHYSICAL ACTIVITY, AGAIN
MOST STUDIES ON INTERMITTENT
FASTING FIND NEITHER POSITIVE
NOR NEGATIVE EFFECTS ON PHYSICAL
ACTIVITY.
CHRISTA VERDE AS LOOKED AT
TIMING OF PHYSICAL ACTIVITY AND
INTERACTION WITH FASTING.
I THINK IN THE CONTEXT OF
ALTERNATE DAY MODIFIED FASTING.
ON FOOD INTAKE MOST OF THE
STUDIES SUGGEST NO MAJOR CHANGES
IN DIET QUALITY, SO SOME
STUDIES -- MAYBE TWO STUDIES
SUGGESTED SOME PEOPLE ARE
CONSUMING LESS ALCOHOL WHICH
PERHAPS IS NOT SURPRISING, A
GOOD THING.
AND I THINK ONE STUDY FOUND LESS
CARBOHYDRATE INTAKE THAT WE
WEREN'T ABLE TO REPLICATE.
WE FIND PEOPLE JUST TAKE THE
SAME EATING HABITS AND CONDENSE
INTO A SHORTER EATING PERIOD AND
DON'T SEE CHANGES IN DIET
QUALITY, THEY SEEM TO BE
SEPARATE DOMAINS, THE MEAL
TIMING, VERSE U.S. -- VERSUS
DIET QUALITY.
>> THAT BRINGS UP ANOTHER
QUESTION THAT RESONATES WITH
Q&A.
A LOT OF STUDIES HAVE BEEN DONE
IN OVERWEIGHT OR OBESITY
POPULATIONS, RIGHT?
WHAT ARE THE EFFECTS OR THE
POTENTIAL EFFECTS OF
TIME-RESTRICTED EATING IN NORMAL
WEIGHT INDIVIDUALS?
>> GREAT QUESTION.
SLIGHTLY HARDER QUESTION BECAUSE
OF THE LEVEL OF NUANCE REQUIRED
TO ANSWER.
GENERALLY HEALTHY POPULATIONS
IT'S GENERALLY HARDER TO SEE
EFFECT BECAUSE THE BODY IS A
WONDERFUL HOMEO STAT, BLOOD
SUGAR IS PERFECT, IT'S NOT GOING
TO PUSH THAT LOWER.
I'M PART OF A STUDY FUNDED BY
THE NIA, SITE P.I., WE'RE
LOOKING AT HEALTHY INDIVIDUALS,
WHETHER THIS CAN SLOW BIOMARKERS
OF AGING, ENDPOINTS WITH STEM
CELL PRODUCTION, TELOMERE
LENGTH, MOLECULAR CHANGES.
MY LAB HAS FOUND CHANGES IN
AUTOPHAGY, MARKERS OF OXIDATEIVE
STRESSES, CERT 1 SIGNALING, A
GENE RELATED TO LONGEVITY.
WE DID FIND ALTERATIONS IN
CORTISOL PRODUCTION.
MY GUESS IS THESE WOULD
EXTRAPOLATE TO HEALTHY
POPULATIONS, THESE TYPE OF
EFFECTS.
>> VERY COOL.
THAT LEADS INTO A DIFFERENT
TOPIC OF AUTOPHAGY AND THEN ALSO
IMMUNE RESPONSIVENESS, RIGHT?
SO, IS THERE A LOT OF
INFORMATION ON HOW THESE DIETS
IMPACT IMMUNE RESPONSIVE
AUTOPHAGY, INFLAMMATION,
PHYSIOLOGIC SIGNALS THAT PREEMPT
BODY REPAIR?
>> IN HUMANS, NO.
IT'S HARD TO MEASURE IN HUMANS,
OTHER THAN TO MEASURE GENE
EXPRESSION, I THINK MY LAB MAY
BE ONE OTHER LAB HAS BEEN ONLY
ONE TO MEASURE AUTOPHAGY-RELATED
END POINTS.
ON IMMUNE SYSTEM FUNCTION THAT
DATA IS MIXED.
I CAN'T MAKE SENSE OF WHETHER
THERE SEEMS TO BE A TREND
TOWARDS NULL OR POSITIVE
FINDINGS.
IN ANIMALS, THERE'S BEEN SOME
REALLY FASCINATING WORK THAT'S
COME LARGELY FROM THE COMMUNITY
OF CANCER RESEARCHERS THAT SHOW
SHIFT IN T CELL POPULATIONS,
RESPONSE TO INTERMITTENT FASTING
PARTICULARLY FASTING MIMICKING
DIET THAT FAVOR ANTITUMOR
IMMUNITY.
SO I'M NOT AN EXPERT IN THIS
FIELD I DON'T WANT TO BUTCHER
THE FINDINGS BUT THAT'S TRUE.
THERE HAVE BEEN OTHER VERY
POSITIVE IMMUNOLOGIC FINDINGS AS
WELL.
>> VERY INTERESTING.
A LITTLE HOPEFUL, RIGHT?
THERE SEEMS TO BE A LOT COMING
IN ABOUT OVERARCHING BENEFITS OF
PAYING ATTENTION TO THE TIME OF
DAY YOU TAKE IN YOUR ENERGY, HOW
THE BODY HAS DEVELOPED IN ORDER
TO PRIORITIZE THE INTAKE OF
ENERGY VERSUS THE USE OF ENERGY
THROUGHOUT THE DAY.
>> I THINK THE MECHANISM --
WE'LL FIND THE MECHANISMS ARE
HETEROGENEOUS, AND SOME COULD
LOOSELY RELATED TO CIRCADIAN
SYSTEMS, SOME MAY NOT BE.
IT WILL BE A RICH FIELD AND
CONTINUE TO BE SO IN THE FUTURE.
>> WELL, FANTASTIC.
ONE MORE QUESTION.
ALIGNS WITH ONE OF OUR CRITICAL
OPPORTUNITIES IN THE NIH SLEEP
RESEARCH PLAN.
SPECIFICALLY, SHOULD THE MEAL
TIME OFF, MEAL TIME OFF, BE
BASED ON A TYPICAL BEDTIME OR
ULTIMATELY IS THERE A MORE
SPECIFIC BIOMARKER OF ENDOGENOUS
CIRCADIAN RHYTHM, LET'S SAY DIM
LIGHT, MELATONIN ONSET, THE OR
MONEY THAT HELPS DRIVE THAT
SLEEP NEED, OR THAT SLEEP WANT,
IN THE EVENING.
THAT WOULD BE A BETTER TIME WHEN
TO STOP EATING?
>> GREAT QUESTION.
YOU CAN IMAGINE ALL KINDS OF
VERY FRUITFUL PUBLIC HEALTH
RECOMMENDATIONS BASED ON CUTOFF
TIME.
SO, THIS IS ACTUALLY ALSO AN
AREA OF RESEARCH THAT'S POPULAR
IN EPIDEMIOLOGIC RESEARCH.
STARTING TO SEE A NUMBER OF
STUDIES COMING THROUGH THE
PIPELINE WHERE PEOPLE ARE ASKING
WHAT IS THE OPTIMAL CUTOFF FROM
A POPULATION HEALTH PERSPECTIVE.
I CAN TELL YOU MECHANISTICALLY
WE KNOW AS SOON AS MELATONIN
LEVELS ARE ELEVATED THAT INDUCES
INSULIN RESISTANCE.
WE EXPECT THAT INFORMATION ON
DIM LIGHT MELATONIN ONSET OR
WHEN LEVELS START TO RISE IN
PEOPLE WOULD BE REALLY IMPORTANT
IN DETERMINING CUTOFF.
BUT I DON'T THINK WE KNOW ENOUGH
TO EXACTLY KNOW WHERE TO PUT
THAT.
SO I THINK THIS IS SUCH A GREAT
QUESTION.
IN PARALLEL THERE'S A LINE OF
FIELD DEVELOPING, YOU MENTIONED
A BIOMARKERS TO MEASURE EACH
PERSON'S RHYTHM.
I SAW GREAT QUESTIONS ABOUT
PERSONALIZING IN A.
THERE'S GOING TO BE AN IMPORTANT
ROLE FOR PRECISION NUTRITION
BASED ON UNDERLYING CIRCADIAN
RHYTHMS.
EXCITING PROGRESS BUT THE
PRECISION IS NOT THERE YET IS MY
UNDERSTANDING, IN TERMS OF
DEVELOPING A SINGLE BIOMARKER
FROM A BLOOD SAMPLE, BUT VERY
COOL WORK BEING DONE IN THAT
AREA.
LET ME ADD ONE CAVEAT.
ONE THING TO THINK ABOUT IS
WHICH CIRCADIAN RHYTHMS ARE
MALLEABLE.
THERE'S A REALLY GOOD BODY OF
DATA SUGGESTING THAT GLYCEMIC
CONTROL IN INDIVIDUALS WITH TYPE
2 DIABETES PEAKS IN THE EVENING,
THERE'S A NICE STUDY OUT OF
CHINA SHOWING AROUND INSULIN
SENSITIVITY PEAKS AROUND 7:00
P.M.
YOU THINK MAYBE WE SHOULD SHIFT
FOOD INTAKE TO THE EVENING FOR
FOLKS WITH TYPE 2 DIABETES BUT
RESEARCH SHOWS THEY TEND TO
BENEFIT FROM EATING EARLY IN THE
DAY SO MAYBE IT'S A MISALIGNED
RHYTHM THAT NEEDS TO BE
CORRECTED.
JUST BECAUSE RHYTHM PEAKS OR AT
A DIFFERENT TIME OF DAY WE DON'T
KNOW THE DEGREE THAT'S INTRINSIC
VERSUS MALLEABLE OR THERE'S MORE
WORK TO BE DONE IN A THAT AREA
AND THERE MAY BE MORE
MALLEABILITY THAN WE THINK.
>> A LOT TO UNPACK HERE.
IT SEEMS LIKE THERE'S A TON OF
OPPORTUNITY FOR NEW RESEARCH
THAT'S GOING TO LEAD TO REALLY
GREAT PUBLIC HEALTH
RECOMMENDATIONS IN THE FUTURE.
IT'S GREAT THIS IS SOMETHING
THAT PEOPLE CAN DO BEHAVIORALLY.
SO IT'S NOT GOING TO BE
DEPENDENT ON MAKING SURE YOU'RE
KEEPING UP WITH YOUR MEDICATION,
ALSO IMPORTANT, BUT SOMETHING WE
CAN START TO DO FOR YOURSELF,
PAY ATTENTION FOR YOURSELF TO
BENEFIT YOUR FUTURE HEALTH.
>> YES.
>> I DO WANT TO SAY THANK YOU
SO MUCH FOR THIS -- FOR SHARING
AMAZING INSIGHTS ON THIS TOPIC.
I THANK EVERYONE FOR JOINING,
STAYING ON, CONTRIBUTING TO THE
QUESTIONS.
I'LL PLUG THE WORKSHOP ON
CHRONONUTRITION, MAY 2 AND MAY
3.
FIND THE INFORMATION ON THE
NHLBI PUBLIC WEBSITE UNDER
EVENTS.
PLEASE STAY TUNED FOR FUTURE
ONPI SEMINARS LATER THIS YEAR.
I HOPE EVERYONE HAS GOTTEN
SOMETHING WONDERFUL OUT OF THE
PRESENTATION AND HAS A WONDERFUL
REST OF YOUR DAY.