January 13, 2020


#88 – Paul Grewal, M.D.: Treating metabolic disease and strategies for long-term health

“You could say our food supply has changed more in the last 100 years than it has in the last 10,000." — Paul Grewal

Read Time 46 minutes

In this episode, Paul Grewal, internal medicine physician and co-author of Genius Foods, discusses what has got him so focused on lifestyle changes for metabolic health which was partly brought on by his own experience of losing almost 100 pounds at two points in his life. Paul and Peter discuss how the results from a NuSI-funded study has impacted their feelings about the supposed “metabolic advantage” of a low-carb diet. Paul then makes the case for what he calls the “active poisoning” of the American food supply, defines his five phenotypes of obesity manifestation, as well as lays out his nutritional and training approach with his patients (as well as himself personally). Overall, this discussion is a treasure trove of topics from endocrinology, insulin resistance, caloric restriction, fasting, exercise, causes of obesity, LDL and heart disease, and much more. 


We discuss:

  • Paul’s health story—two instances of major weight loss [3:15];
  • The multiplication of adipocytes after weight loss, and why an obese adult that was overweight in childhood is harder to treat than adult-onset obesity [7:30];
  • Low-carb diets—Is there a metabolic advantage in energy expenditure? (And Peter’s take on the NUSI study) [12:45];
  • The relationship between hyperinsulinemia and hyperglycemia—which is causing which? [27:00];
  • Weight gain—Which macronutrients are driving it, processed foods, and overfeeding studies [31:15];
  • The active poisoning of our food supply with processed foods [36:15];
  • The role of fructose in metabolic disease and NAFLD [39:00];
  • Where traditional medicine falls short in the real world and why “functional medicine” is gaining steam [45:45];
  • Relationship between heart disease and LDL, residual risk, LDL clearance problem, and a patient case study [54:00];
  • Relationship between heart disease and fatty acids (SFA, PUFA, seed oils, etc.) [1:04:30];
  • Paul’s nutritional approach with patients [1:12:30];
  • High-carb/low-fat diet for muscle gain, and the “reverse diet” to combat the slowdown of metabolism after caloric restriction/weight loss [1:15:00];
  • Fasting—ideal duration, how to preserve muscle mass, and the ultimate tool of medicine [1:23:30];
  • The 5 phenotypes of obesity, and the impact of carbs, cortisol, and sleep on adiposity [1:28:30];
  • Uric acid [1:38:15];
  • Paul’s 2nd big physical transformation—How he did it and kept the weight off [1:39:15];
  • Paul and Peter’s personal struggles with food, internal dialogue, and self-image [1:45:00];
  • Paul’s personal nutritional strategy (and how his exercise influences it) [1:52:00];
  • A low-fat diet Peter is willing to try [2:00:40];
  • The keto diet for competitive athletes [2:05:00];
  • How Peter prescribes exercise to his patients [2:08:30];
  • Calculating glycogen depletion and RQ, creatinine-kinase system, Tabata workouts, and more [2:10:30]; and
  • More.


Paul’s health story—two instances of major weight loss [3:15]

  • Dad was from India
  • Mother from Cyprus
  • They met in London, eventually came to America when Paul was young
  • Both his parents put on 15-20 lbs right after moving to the US
  • Fed Paul the “standard diet” not know that “the food supply was being actively polluted or poisoned” 
  • By the time Paul was 12
  • 95th percentile in weight
  • Had an extra 50 or 60 pounds as a 12 year old

I basically have gone through the first half of my life just as what we would describe as a fat person. And that has big effects on self-perception, it has big effects on how others perceive you, and there’s a peculiar American sort of ethos around it being one of the few things that we’re still allowed to be discriminating or discriminatory against.

Paul’s first transformation

  • By the time he was in college he was 275 lbs
  • Went on a caloric restriction diet of ~1200 calories per day
  • Did 6 miles per day on a treadmill
  • Lost 90 lbs
  • But as soon as the stress from med school hit, he gained almost all the weight back

Paul’s second transformation

  • In med school, he managed to lose the weight again with a different approach
  • He’s been able to keep it off since then
  • (More to come on how he did this later)


The multiplication of adipocytes after weight loss, and why an obese adult that was overweight in childhood is harder to treat than adult-onset obesity [7:30]

The multiplication of adipocytes following weight loss

  • Paul says part of the reason that people find it difficult to lose weight after they’ve already lost it and regained it is because…
    • Adipocytes shrink during weight loss
    • But when you regain the weight, they don’t just grow back to normal size, they actually multiply 
    • And then…each one of those fat cells does not stop growing until it’s reached the size of the original adipocyte 
    • It’s a “rubber banding” effect and it becomes more and more difficult to lose the weight

-How significant of weight loss is required to trigger that new expression of adipocytes that instead of simply regaining size, they multiply?

  • Mostly been demonstrated in animal models, says Paul
  • Probably has to do with the body’s counter-regulatory mechanisms to prevent weight loss
  • Paul’s suspicion would be that once those start to kick in that there’s probably some epigenetic changes that dictate that
  • But I don’t think it’s quantifiable at this point.
  • Peter’s says it seems imminently testable by taking fat biopsies of people during a period of weight reduction and weight regain
  • (Peter wonders if Rudy Leibel has tested this)

Why childhood obesity seems harder to treat

-Paul observes different phenotypes of overweight people in his clinical practice…

{end of show notes preview}

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Paul Grewal, M.D.

Dr. Paul Grewal is a board-certified Internal Medicine physician serving patients in the Upper East Side, New York, New York. Dr. Paul Grewal provides a variety of services to patients at MyMD Medical Group, including holistic and integrative health, preventive care, and vaccinations.

Dr. Paul Grewal earned a Bachelor of Arts in Cellular and Molecular Neuroscience from Johns Hopkins University. After graduating, he went on to study medicine at Rutgers, New Jersey Medical School. He completed his residency at North Shore-Long Island Jewish Hospital.

Dr. Paul Grewal has a keen interest in the holistic prevention and treatment of disease. He takes great pride in helping his patients with their individual health needs, from reversing diseases like type 2 diabetes to losing weight or managing their hormones.  

In his spare time, Dr. Paul Grewal enjoys spending time on the only pull-up bar in Central Park. [mymd.nyc]

Disclaimer: This blog is for general informational purposes only and does not constitute the practice of medicine, nursing or other professional health care services, including the giving of medical advice, and no doctor/patient relationship is formed. The use of information on this blog or materials linked from this blog is at the user's own risk. The content of this blog is not intended to be a substitute for professional medical advice, diagnosis, or treatment. Users should not disregard, or delay in obtaining, medical advice for any medical condition they may have, and should seek the assistance of their health care professionals for any such conditions.


  1. Even with the warning, the balance of talking between you and your guest made me wonder why you bother to have guests at all! The mic balance is off too – your voice is very loud and your guest hard to hear. There’s probably a great narrative in there somewhere but it’s hard to follow.

  2. Dr.Attia.
    I have fasted a lot.over 4 years. I started fasting 1 day on month 1 and kept adding a day every month till I fasted 10 days in a row in month 10. Only water or black coffee. My body odour eventually disappeared all the time, even during fasts. I tested prolonged time between showering to see if something was going on in the way of bacteria or something. I could routinely shower every three days as an experiment without experiencing body odour of any amount. I agree with fasting being the the greatest healing modality ever. I now fast till my age spots disappear off my face. This requires different lengths of time and the time depends on, what I think, is food in my digestive tract. The cleanout, as I call it, seems to start at 1 to 1.5 mmol of ketones as seen with blood stick. Seeing my age spots disappear never occurs till I am in Ketosis and then within the next 3 to 4 days. So the clean out only occurs after the glucose depletion and ketone production begins. So age spot obliteration can take 5 to 7 days fasting. Time to fast again now is often triggered with their appearance.

  3. Another great podcast. I liked that Paul got you into some pattycakes. Felt like one of your AMA’s.

    The most intriguing part of the podcast was the discussion around the potato only diet. The excess carbs staying in the system. Does that mean that if you’ve exhausted your ability to store glycogen, excess glucose just circulates in your blood, being drawn down as needed to fuel normal energy demands? If pyruvate dehydrogenase is overwhelmed, are we shunting more glucose to the pentose phosphate pathway? What are the implications of this? Over time, would we see an upregulation in genes associated with de novo lipogenesis in response to such a diet to increase flux through glycolysis?

  4. What an interesting and engaging dialogue! I actually enjoyed this format of a conversation rather than interview;-)) Quick question: when talking about the dangers of high cholesterol, what was the measurement that Dr Attia mentioned – it sounded like “PNPLA”, is that correct? I couldn’t make it out. Thnx!

  5. I enjoyed your podcast. What is your opinion of resistant starch? It is low glycemic, prebiotic, and has >240 clinical trials showing numerous metabolic health benefits. It’s fermentation in the large intestine changes the expression of more than 200 genes in the large intestine, including GLP-1, PYY. Almost 20 clinicals have studied its effect on insulin – in general, it increases insulin sensitivity, and FDA approved a qualified health claim 3 years ago that resistant starch reduces the risk of type 2 diabetes. I especially liked your information about food poisoning – it matches the arguments I’ve been making that people used to eat 30-50 grams of resistant starch/day but with food processing over the past 100 years, it is destroyed and we are now getting only 5-6 grams, which starves our microbiota and triggers insulin resistance, leaky gut, obesity and lots more. It is almost like we are strongly agreeing from different perspectives.

  6. Hi guys great talk – as usual.
    I was wondering about the cortisol question – and the context of catabolic vs anabolic. Could it be that when we see the tiger we get a rush of other hormones simultaneously, e.g. catecholamines, alongside the spike in cortisol and that’s what causes liberation of energy? I’m not aware of a big catecholamine production in chronic stress, but I could be wrong.
    When we give patients high doses of prednisolone for say PMR or TA, they usually don’t get leaner.
    Thanks for all your work!

  7. Also when I made my first run at loosing weight I went from 240 to 195 with intense calorie resetriction, not because I had planned it but because I was on some bizzare mental snap. Exercising twice daily with runs and aerobic classes. Severe calorie restriction just because I was on a mission. I dropped the weight in 5 months and was muscular. This was 1982 so no one though of dexa scans. I was toned. I still needed to drop another 15 lbs I guess but I never did. I spent my entire childhood obese. This intense intervention at 22 brought me through the following 20 years of no exercise nor concern of what I was eating but my weight stayed stable. In my mid 40’s it started to creep. I feel that was the drop in muscle and slow insidious creep in insulin sensitivity. I believe I managed to regain insulin sensitivity during my intense bizzare mental diet exercise breakdown. My post 40 weight gain followed a slowly ascending curve getting steeper with time. I hit 240 again and this time took 4 years(intentionally) to drop it with periods of fasting and no exercise. I am at 200 lbs simply focusing on shying away from simple carbs, not drinking carbs and fasting. 4 years and monthly 72 to 120 hour water fasts with an occasional 168 tossed in for fun, I find them easy to do now. I am currently aiming for a 168, the age spots on my face didn’t respond to last months 96 but they will, they always do. I feel this is the way to do it for me-go till the spots go. I wonder if there was some other metric I could measure, me, not a lab that would express something that happens beyond the age spots.

  8. Great interview. The Randle cycle is the most important factor in metabolic health. They spoke about it for an hour but never refered to it once as the Randle Cycle (glucose/fatty acid cycle).

  9. another great podcast – the combination of this with the last 2 ( fructose and mitochondrial health) gives a really comprehensive picture of what we ( sort of ) know now. Stringing it all together is the challenge. It would be good in the future ( if the evidence becomes clearer) to discuss the possible differences between men and women in terms of their responses to difference macros and metabolic efficiency. I also note that alot of what Paul was saying today kind of sounded like the Slimming World protocol – carbs and protein/fat and protein – but not together. I have always dismissed this but know people who swear by it. Also to Peter’s lament as to how to eat carbs without fat – a really good slow cooked tomato ( or aubergine/tomato/courgette) sauce with lots of garlic on pasta works v well – you hardly need any oil – and risotto with fat skimmed real chicken broth and spring vegetables is delicious and you can do it with v little fat – anyway – that kind of thing – carbs with wet veg sauces etc

  10. Great podcast. I for one, want to hear your thoughts as well as the guests. I loved the two way interaction in this podcast. This give a more well rounded view on the subject matter, rather than just one persons.
    Keep it up!

  11. Thank you for teaching me so much during this episode. I tried to complete a 72-hour fast last summer after listening to the entire Tom Dayspring set, but I was teaching gen chem and after 69 hours, I realized I could no longer do simple arithmetic in front of my students. I was only in ketosis for 8 days when I started and I was not exercising that week. I have been afraid to fast for such a long amount of time since then, but perhaps there are other strategies I can try. I also teach physics now so I am extremely concerned about my brain shutting down on a fast! I suspect that fasts are different for women than men. Are there any women who have fasted for over 72 hours with better results?

  12. Re: the question of whether hyperglycemia is a product of hyperinsulinemia or vice-versa, and especially on high levels of glucose being incredibly destructive: patients with glucokinase–maturity-onset diabetes of the young (GCK-MODY) have a mutation that causes their pancreas to greatly delay the release of insulin in response to rising glucose levels, leaving to chronic hyperglycemia with no accompanying hyperinsulinemia — and they have no adverse outcomes, so the recommended medical management is to do exactly nothing about it.
    “GCK-MODY do not develop significant microvascular complications, and the prevalence of macrovascular complications is probably similar to that in the general population. Treatment is not recommended outside pregnancy because glucoselowering therapy is ineffective in people with GCK-MODY and there is a lack of long-term complications ”
    Diabetes Care 2015;38:1383–1392 | DOI: 10.2337/dc14-2769

  13. I’m your n=4!!

    I’ve been TRE for the past 2 years, fairly low carb, regular exercise. I’ve lost a little weight but I’d still like to lose about 20 more pounds (currently 5’7″ 170 lbs)

    However…my sleep is crap. It has been for the past 8-10 years which is when I started putting on stubborn weight that I have trouble taking off. (I’m 46 years old now..pre-menopausal). The biggest clue for me about my cortisol levels being out of whack is the fact that for years I have had an overwhelming crushing need to take a nap around 3:30 in the afternoon. If I’m not at work I’ll sleep for 2 hours and wake up feeling disoriented. On the flip side, I would wake up at 3 am or so and be wide awake…almost like I was buzzing on caffeine. Could not fall asleep til around 5. Wake up at 7:30 and repeat the cycle all over again. A1C 5.2, normal thyroid functions. I will say that with the time restricted eating things have gotten better and my sleep is normalizing, but when I listened to this podcast the other day and you described your 3 female patients who had trouble losing weight I was like “that’s me!!”

    Just wanted to share my story…I do feel that my metabolism is healing although it is a slow process. Thanks for all you do!

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