Is "overeating" the cause or consequence of getting fat?
Human studies are too short to provide an answer. So we reviewed the animal research.
👉In almost every case, evidence shows an underlying metabolic problem driving the positive energy balance
#CIM
Are all calories alike to the body? Our new feeding study – among the largest ever done – suggests not. A low-carbohydrate diet sped up metabolism by ≈ 250 calories a day. This effect could help weight loss maintenance. Free access to study linked here:
Insulin was discovered in 1921.
Previously, a low-carb diet was the mainstay of treatment for all types of diabetes.
Afterwards, high-carb diets became popular, but not because of evidence of superiority
👉Time to rediscover centuries-old wisdom on diet
Said about a ketogenic diet:
1979: Such high fat intake will make you fat
1999: You might not get fat but you'll get heart disease
2019: You might not get heart disease, but it has severe side-effects
👉My new review of the science (full free access):
Nearing the 100th anniversary of insulin's discovery:
👉Original rights sold for $1. "Insulin...belongs to the world"
👉Yet Americans pay $100s/mo for this lifesaving drug
👉$300 insulin in US costs $20 in Canada
@NEJM
calls for solution to this crisis
In a major new review, traditional hunter-gatherers seen free of obesity/diabetes, even though many lived to old-age. EXPLANATION?
>Not calorie expenditure
>Not meat vs plants
>Not fat vs carbs
👉No processed, fast-digesting carbs (except honey)
Are all calories alike to the body? Or are fast-digesting carbs including refined grains and sugar uniquely fattening? Our review of the Carbohydrate-Insulin Model of obesity selected Top Article of 2018 in
@JAMAInternalMed
. Full free access available here
A new genetic study from our Boston team supports a key tenet of the Carbohydrate-Insulin Model. High insulin secretion throughout life predicts weight gain, not the other way around. See my nontechnical summary with links to the full article and editorial
How do carbs affect the brain?
In one of the biggest feeding studies of this Q, a low-carb (20% cals) diet ⬇️ brain activity in:
👉 Nucleus accumbens ("addiction center")
👉 Hypothalamus (controls hunger & metabolism)
👉 Effects related to ins secretion
A meta-analysis found that high carb diets slow metabolism:
How might this happen?
👉In a new study, mitochondrial respiration in fat tissue was suppressed on a 60% carb diet (vs 20 or 40% carb)
Findings preliminary.
Open access:
In preparation for gastric bypass, a 4-week ketogenic diet produced "highly significant" decreases in:
> Body fat (15-18%)
> Glucose
> LDL cholesterol
> Triglycerides
> Liver size
Diet had high acceptability
SO WHY NOT STAY ON THE DIET AND SKIP THE BYPASS?
Intermittent fasting for type 1 diabetes? Goes against everything I was taught to teach my patients. But this approach, and low carb diets, hold promise for a new era of diabetes control (types 1 & 2). NEEDED: clinical trials of novel diets, not just drugs
To paraphrase Mark Twain:
Reports of the death of the Carbohydrate-Insulin Model have been exaggerated.
👉17-author review
@AJCNutrition
👉Deep dive on obesity mechanisms
👉Numerous hypotheses to guide constructive debate
Free text👉
Thread (0/12)👇
Breakfast in the classroom INCREASED obesity rates among grade school children. Perhaps the problem isn't breakfast, but the poor quality (processed carbs) typical of school food?
👉"intervention schools ... offered only cold items (eg, cereal, muffins)."
Do low-carb diets speed up metabolism?
👉For 2 weeks, no, as the body adapts.
👉After that, yes. Cutting carbs in half on a typical diet seems to increase energy expenditure ~ 150 cal/day.
👉👉Meta-analysis in March issue
@jnutritionorg
Free full text
Do high-fat diets cause obesity?
Rodents gain weight on high-fat diets. But these typically also have sugar and other fast digesting carbs.
👉Turns out, the problem is the sugar, not fat, through effects on gut microbiome, according to a major new study.
After >12 papers claiming to disprove the Carbohydrate-Insulin Model of obesity:
First full formulation of the model now in press at a major journal.
👉International team of 17 coauthors
👉5000 words
👉>150 references
👉online supplement
Looking forward to constructive debate!
New 5-month feeding study, N=164, supported by NuSI,
@Arnold_Ventures
Low carb (20%) vs high carb (60%) diet improved:
👉Lipoprotein insulin resistance
👉Lp(a)
👉Adiponectin
And no LDL-chol increase (with high sat fat, 21 vs 7%)
Open access full text 👇
Are all calories alike to the body? Or are processed carbohydrates - think white bread, potato products and sugar - uniquely fattening? Our new review on the Carbohydrate-Insulin Model & related controversies
@JAMAInternalMed
(free text available for 1 wk)
In a 14-year study, blood sugar was the only cardiometabolic predictor of dementia. Alzheimers has been called "type 3 diabetes" recognizing that problems using glucose may contribute to this disease. Would maintenance of insulin sensitivity be preventive?
Intermittent Fasting Review:
"Ketone bodies are not just fuel...[they] regulate the expression and activity of many proteins and molecules that are known to influence health and aging"
How can you raise ketones without hunger/fasting?
👉Ketogenic Diet
How might a high-carb diet drive fat storage, increase hunger and slow metabolism?
Our new study assessed calories in the blood available to fuel metabolism after eating.
Following an initial surge, calories crashed on a high-carb diet.
Free Full Text👇
New research shows that triglycerides (circulating fat in the blood) crosses the blood-brain barrier and interferes with actions of the satiety hormone leptin. One of the most effective ways to lower triglycerides – a low-carb/ high-fat diet (really!)
Can you eat more on a lower carb diet without gaining more weight?
👉New data from our large feeding study (≈100k meals over 5 months) suggest so
👉Results support prior findings that reducing carb intake may increase calorie expenditure
Free text👇
DASH is generally rated best for high blood pressure
In this 4-month trial a Very-Low-Carb (ketogenic) diet was superior to DASH:
👉Sys BP (10 vs 5 mm Hg)
👉Wt loss (19 vs 10 lb)
👉HbA1c (0.35 vs 0.14%)
👉⬇️drug usage
More reason for a large-scale trial!
New clinical trial compared a low-carb diet (eat as much as you want) versus a low-fat diet (calorie restricted). Both groups otherwise treated similarly. At 1 year, low-carb had:
Lower weight
Lower HgA1c
Better ratio of trig/HDLc
(Full text available)
Critics of the Carbohydrate-Insulin Model built a new Energy Balance Model of obesity.
My 15 coauthors and I have a few thoughts about it.
@ejcneditor
@SpringerNature
#CarbInsulinModel
New review open access at this link 👇👇👇
Thread 1/16
Do low carb diets speed up metabolism? Our study in
@bmj_latest
last year suggests so.
Upon publication, one group criticized us in lectures, social media etc.
👉We now show these criticisms are misleading or simply wrong
@IntJObesity
Free text link👇
Should everyone drink 3 glasses/d reduced-fat milk? Our review
@NEJM
finds NO evidence that:
👉Milk strengthens bones
👉Reduces risk for obesity, heart dx
👉Lowfat is better
Probably fine to have 1 - 2 servings/d. Enjoy the full-fat versions!
Blog here:
Can researchers with opposing views of dietary fat vs carbohydrate work together in the interests of science and public health? Yes, with respectful dialogue and willingness to seek common ground. See our review in Science Mag (full text freely available):
Our new study documents exceptional blood sugar control, with low complications rates, among children and adults with type 1 diabetes on a very-low-carb diet. We need clinical trials of this exciting approach. See my blog for a summary and study links
Ketones are good for the brain. Now it seems they’re good for the heart, too (in this study, for heart failure). But you don’t need an IV infusion. Carb restriction will do.
Been saying this for a long time, we need a trial with keto diet for CHF... like yesterday
👇🏻👇🏻👇🏻👇🏻👇🏻👇🏻👇🏻
Cardiovascular Effects of Treatment with the Ketone Body 3-Hydroxybutyrate in Chronic Heart Failure Patients | Circulation
Should we scale back COVID-19 prevention? Some suggest focusing only on most vulnerable. Let everyone else return to normal life
👉But this would be disastrous,
@rickmalley
& I argue
@nytopinion
👉With >80% US "metabolically unhealthy" we're all at risk
How useful is the century-long focus on calorie balance? Eating just 10% less and exercising a bit more should lead to major weight loss after a few years. But it rarely does. A deep dive by the
@TheEconomist
More US adults say they are exercising according to new data, even as obesity rates continue upwards. Physical activity has many benefits. But as
@TimNoakes
says, you can't outrun a bad diet.
American Diabetes Association dietary recs, 2022
SAME: "There is no ideal macronutrient pattern for people with diabetes"
NEW: "Reducing overall carbohydrate intake for individuals with diabetes has demonstrated the most evidence for improving glycemia"
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HOW you lose weight may be as important as HOW MUCH you lose
In new study, those with tendency to secrete lots of insulin lost:
👉less body fat
👉more lean tissue
Finding may identify group at risk for wt regain with strict calorie restriction
Free text:
American Diabetes Association released a new report on sky-rocketing cost of insulin, including recommendations for cost containment. Not mentioned: Reduce consumption of processed carbs (which require more insulin than any other food, calorie for calorie)
A new study on COFFEE reported:
"22% lower risk of mortality for each 2 additional cups of coffee/day"
👉"This association was stronger for participants aged ≥55"
👉👉Looks like there's at least one advantage of aging
Our study on benefits of reducing carbs was dismissed by vegan groups
@PCRM
. But it's not about PLANT vs ANIMAL diet.
One can eat low-fat with chicken breast, egg whites, low-fat cheese.
Or low-carb with olive oil, nuts, avocado.
👉Let's seek common ground
GHRELIN is a hormone made in the stomach that causes hunger. In a new study, eating processed carbohydrates in a meal LAST, rather than FIRST, resulted in significantly lower ghrelin 3 hr later (when you might be otherwise tempted to have that extra snack)
Low-carbohydrate diets gaining attention from Canadian Diabetes Association.
👉A major shift from the 20% fat / 60% carbohydrate diet recommended by most diabetes associations a few decades ago.
International Tables of Glycemic Index and Glycemic Load 2021 now published!
Updated from the last (2008) edition
Includes >4000 items
👉 Important data to facilitate rigorous research
@AJCNutrition
@nutritionorg
Julia, the main attack against our study is baseless. The baseline value for energy expenditure was obtained BEFORE RANDOMIZATION, so any "noise" from individual changes (eg weight) won't bias results toward any diet.
👉This is Statistics 101
👉Please post a correction
@ezraklein
My latest on that big, new low-carb study:
It won't end the debate — but it is a reminder that the discussion about diet studies increasingly resembles political tribalism.
Drugs that lower insulin (diazoxide, in this new trial) cause weight loss😀
Drugs that raise insulin (eg, sulfonylureas) cause weight gain😟
Is it a stretch to infer how low vs high carb diets (that lower vs raise insulin) would affect weight?🤔
A short opinion piece in Science claims to have "refuted" the Carbohydrate-Insulin Model of obesity.
This brings to at least a dozen the number of recent dismissive reviews, based on the same weak studies.
My thoughts 👇👇👇
Equating a positive energy balance with weight gain
👉"is like saying the only way to make money in the stock market is to buy low and sell high – an observation that, while true, is meaningless as an investment strategy"
New review of Carb-Insulin Model
All saturated fats are not alike. Palmitic acid (C16) is linked to heart & other chronic disease. But stearic acid (C18) may reduce risk. In a new study, C18 improved function of human mitochondria, the center of metabolism.
Note, dark chocolate has C18 👌
High INSULIN SECRETION associated with more body fat, metabolic dysfunction as predicted by the Carb-Insulin Model. High insulin secretors at higher (not lower) diabetes risk.
Study strength: control for INSULIN RESISTANCE
Limitation: observational design
In type 2 diabetes, melatonin (the hormone related to sleep) at 10 mg/day for 3 months, improved markers of:
Inflammation
Oxidative stress
Diabetes control
Heart disease risk
These results remarkable results, from a double-blind trial, demand more study
10 years ago
@marionnestle
& I wrote a piece for JAMA considering the "dark side" of food industry behavior related to obesity. Newly leaked documents suggest these behaviors continue, with cereal manufacturers seeming to buy influence and target opponents
Ok folks.
@drjkahn
is a leading advocate of vegan diet (aiming to eliminate all animal products).
@SBakerMD
is a leading advocate of carnivore diet (aiming to eliminate plant products). If they can hold a respectful discourse, maybe there’s hope for the rest of us.
Exercise has metabolic similarity to a low-carb diet:
⬇️ insulin
⬆️ lipid oxidation
⬇️ glycogen
👉NEW REVIEW: "performing [exercise] in an overnight fasted state (i.e. before consumption of carbohydrate), may provide additional metabolic health benefits"
In major genetic study
👉⬆️ body fat occurs BEFORE ⬆️calorie intake
👉obesity dependent on high insulin secretion
👉evidence for relevance to human obesity
Result
👉"differs from the dogmatic view"
👉fulfills key predictions of
#CarbohydrateInsulinModel
In new large study (>100k adults, 24 yr), most carbs associated with major weight gain
For those with
#obesity
, EVERY 4 YR:
👉Total carb 0.8 kg
👉Starch 4 kg (!)
👉Sugar 1.9 kg
👉Glycemic index 2.8 kg
👉Fiber protective
Pretty much per carb-insulin model
"With the cost of just one weight-related complication, diabetes, almost $1 billion a day, we must consider different ways of solving the intractable problem of obesity and open our minds to a radical-sounding notion: Overeating is a symptom, not a cause."
Intriguing new study in humans and mice. Triglycerides pass the blood brain barrier and cause hypothalamic leptin/insulin resistance, lowing satiety. Decreasing trigs with a drug had cognitive benefits. Another effective treatment: a lower carb diet.
Elliot Joslin, diabetes expert, in 1905:
"A diabetic diet is really an ordinary diet in which the carbohydrates are replaced by fat"
"The diabetic's chance for life depends upon his ability to eat fat"
Regarding cream, best to increase "up to half a pint"
(Now called NEJM 👇)
Insulin was discovered in 1921.
Previously, a low-carb diet was the mainstay of treatment for all types of diabetes.
Afterwards, high-carb diets became popular, but not because of evidence of superiority
👉Time to rediscover centuries-old wisdom on diet
IN 1920 (before insulin), famous obesity researchers wrote "we have dared to ignore the belief concerning the danger of fat in the diet of diabetics". With a high-fat diet, they "succeeded in rendering and keeping every patient" free of sugar in the urine
Our 2018 study showed higher calorie burn on a low-carb diet
We recently responded to wide-ranging criticisms from one group
👉Here we show why their remaining criticism is premised on statistical error
Hormonal modulation by DIET for CANCER?
A very-low-carb, ketogenic diet "greatly enhance(d) the efficacy/toxicity ratios" of a promising cancer drug, as seen in rodents. Authors say findings raise concern for giving"glucose-laden" foods to cancer patients
50th Anniversary of Unger's Seminal Paper on Glucagon:
👉Insulin is a hormone of energy storage
👉Glucagon is a hormone of energy release
👉Their ratio determines nutrient balance across fat tissue
Fundamental to Carbohydrate-Insulin Model of obesity
Whole grain consumption caused NO wt loss in meta-analysis of trials. For those with obesity or diabetes, wt GAIN occurred
👉Many whole grains processed, high glycemic load
👉Whole kernel grains (rye, oats, teff) better choices
👉Or ⬇️ total grain intake
New Study:
👉Caffeinated coffee consumption affects blood glucose and insulin more negatively after a poor night's sleep.
Not Studied:
👉The risks of NOT drinking coffee after a poor night's sleep for self and close relatives.
Insulin sensitivity after 36 hr fast:
👉Whole body LESS sensitive
👉Liver MORE sensitive
"insulin secretion disposition indices without taking organ-specific insulin action into account may lead to erroneous conclusions."
Similar to a low-carb diet ...?
How long does it take to adapt to major changes in diet?
Weeks to months, in our new study with continuous glucose monitoring.
👉If you eat low-carb be careful with high-carb splurges
👉If you read research be careful with short diet trials
Open access:
Glycemic Load & Cancer
Rapidly digestible carbs raise insulin more than other foods. Insulin is a growth promoting hormone.
👉Among 100k French studied over ≈8 yr, high GL diet predicted higher overall (25%) and postmenopausal breast (64%) cancer risk.
New study suggests too much insulin, not high blood sugar, drives insulin resistance in T1 diabetes.
👉Insulin resistance is a major risk factor for heart disease.
👉Potential appeal of low-carb diet in diabetes, which greatly lowers insulin requirement.
Impressive results of a trial with 29 military personnel on a ketogenic (calorie unrestricted) vs normal diet. After 12 wk:
Wt Loss: 17 lb
Visceral fat loss: 1 lb
Ins sensitivity: improved
No decr in physical performance
👉Not randomized, needs follow-up
Ketones (β-hydroxybutyrate) in mice increased O2 consumption in fat without similarly increasing ATP production. This combination suggests "metabolic uncoupling" – speeding up calorie burn. The effect might aid weight loss on a ketogenic diet
@BenBikmanPhD
How long does it take to adapt to a ketogenic diet? Weeks to months, according to a major new review.
👉Take it slowly when first starting a low-carb diet
👉Interpret short studies (less than 4 weeks) cautiously!
How long does it take to adapt to a low-carb diet?
Ketones take ≈3 wk to reach stable levels. What about optimal ketone transported into the brain?
👉In animals 6 to 10 wk.
👉Interpret short studies of low-carb diets cautiously.
In one of the first studies of its kind, patients with diabetes received:
Usual treatment focused on drugs OR
A low-carb diet
Beyond needing fewer meds, the low-carb group had:
⬆️wt loss
⬇️hypoglycemia
⬇️diabetes-related distress
👉Time for major trials
In a new meta-analysis of prospective studies, heart disease was associated with processed carbohydrate intake.
👉Glycemic index (relative risk 24%)
👉Glycemic load (44%)
Authors argue "these relations were probably causal" based on Bradford-Hill criteria
What do GLP-1 weight loss drugs reveal about the cause of obesity?
GLP-1 has actions in brain and reduces food intake. Some argue this:
Supports Energy Balance Model
(overeating CAUSES ⬆️ body fat)
Opposes Carbohydrate-Insulin Model
(⬆️ body fat CAUSES overeating)
Thread
1/5
A low-carb diet is sometimes (not always) high in protein. High protein reported to harm kidneys in diabetes.
👉In 143 patients, low-carb helped, not hurt, kidneys
👉Authors call for study of patients with more severe kidney disease
@lowcarbGP
@Dr__Guess
Is "overeating" the main cause of obesity?
New Perspective
@AJCNutrition
@Dmozaffarian
. Since 2000:
Food intake hasn't increased
Phys act hasn't decreased
👉"it is critical for the scientific community to consider alternative explanations (for obesity)"
GLUCOSE & THE BRAIN
On a high carb diet, brain depends on glucose
Glucose metabolism is defective in some brain diseases (Alzheimer's)
Carb restriction (ketogenic diet) can help epilepsy
👉Blocking glucose metabolism may directly improve seizure threshold
$1 Billion! That's the cost to bring 1 drug to market. There are many drugs for many diet-related conditions:
High BP
High blood sugar
Abn lipids
etc
For a tenth the cost of 1 drug, let's run a definitive trial of a low-carb diet for all these conditions
Dairy fat has unique fatty acids that can be measured in the blood. A big study found these fats associated with 30% reduced risk of diabetes among 63,000 participants. Another blow to the long-standing recommendation to avoid full fat dairy?
@Dmozaffarian
Why is nutrition research so often contradictory, inconclusive?
👉Diet is more complicated than drugs, but diet trials less well funded.
👉Our opinion in
@JAMA_current
with Steve Heymsfield, president of
@ObesitySociety
, offers a path forward.
Free text:
Digging into DIETFITS!
In this major trial from 2018, weight loss did not differ on a low-carb vs low-fat
#diet
Does this disprove carb-insulin model of
#obesity
?
In a reanalysis my coauthors and I offer a different interpretation
Open Access Link
1/10
Which comes first, high insulin or obesity?
Conventional view: ⬆️ weight → ⬆️ insulin (ins resistance)
New study: ⬆️ insulin → ⬆️ weight
👉 Raises new possibilities for obesity treatment
👉Consistent with Carb-Insulin Model of Obesity
h/t
@bschermd
The Other Pandemic:
👉"Nearly one in seven American adults now has diabetes, the highest rate on record, a recent study found."
👉"Overweight adults should be screened for Type 2 diabetes ... starting at age 35, five years earlier than currently advised"
Sugary beverage consumption is linked to colon cancer. A major study in susceptible rodents shows that high-fructose corn syrup (glucose + fructose) at moderate dose activated metabolic pathways that promoted tumor size, aggressiveness.
👉Cause for concern
In Episode 9 of
#HTLeadershipStudio
,
@davidludwigmd
, Professor, Pediatrics and Nutrition at Harvard University and Pediatric Endocrinology at Boston Children's Hospital, explains ways to beat a craving for junk food. Watch
.
Ketones show remarkable promise for heart failure, stimulating interest in ketone supplements.
But this requires taking 50 - 100 grams daily.
With available products that's many thousand $ a year.
On a ketogenic diet, liver can make this amount for free
Short summary
#CarbohydrateInsulinModel
"...the difficulty resisting hunger that so many dieters have isn’t a sign of poor discipline, but rather a biological problem involving how our bodies distribute the calories we consume"
👉Read more
@newscientist
:
Long term vegans who become "ethical butchers":
👉Describe health benefit
👉Believe moderate (not high) consumption of animal products from small farms is environmentally sustainable, preferable to industrial grain monoculture
👉👉Timely topic to debate
β-hydroxybutyrate (a ketone) rises on a low-carb diet.
Mendelian randomization study finds people with naturally ⬆️ BOHB have ⬇️ risk for several cancers.
👉 Evidence (with limitations) for a protective effect of carb reduction and fasting for cancer...?
1972 Study:
Subjects with high ketone levels from fasting had NO SYMPTOMS after insulin injection, even with blood sugar DOWN TO 10 MG/DL!!! Authors proposed a ketogenic diet for diabetes. Together with our recent observational study, time for a trial?