A plate of boiled eggs and cottage cheese beside a rolled gauze bandage and a glass of water on a sunlit wooden table

Why Won’t My Wound Heal?

On August 29, 2026August 30, 2026 By Dr. Scott RennieIn Skin & Wound CareLeave a comment

The question comes up on almost every wound follow-up, and it is nearly always phrased the same way. What should I be eating to make this heal faster?

It is a good question. The answer patients get is usually a list of vitamins, which is mostly wrong, or a shrug, which is worse. There is real evidence here. It just does not point where the supplement aisle points.

A healing wound is a construction project

Closing a wound means building tissue. Collagen synthesis, angiogenesis, epithelial migration, immune cell proliferation. All of that runs on amino acids and calories, and the demand is above baseline for as long as the wound is open. A large or chronic wound raises resting energy expenditure meaningfully.

Which means the first question is not which supplement. It is whether the person is eating enough of anything at all. In older adults with a chronic wound, the answer is frequently no, and no capsule fixes an 1,100 calorie a day intake.

What glucose does to the machinery

Hyperglycemia interferes with wound healing at several points at once. Glycosylation impairs neutrophil and macrophage function, which stretches out the inflammatory phase instead of letting the wound progress to proliferation. Fibroblast activity falls. VEGF expression falls, so new vessels are slower to arrive. Matrix metalloproteinase activity rises, which means the collagen that does get laid down is broken down faster than it should be. Collagen density ends up lower.

Put underlying peripheral arterial disease on top and the wound has a supply problem as well as a manufacturing problem.

This is why I care about the A1c on a wound visit and not only on a diabetes visit. The same laceration on a person running an A1c of 11 and a person running a 6 is two different clinical situations, and only one of them is going to close on schedule.

An aside that patients find more persuasive than any of the biochemistry: the glucose control that matters for a wound is the control over the next several weeks, not the number on the day of the injury. That is actionable. It gives someone something to do about a wound that is already there.

The protein number

For adults with a pressure injury who are malnourished or at risk of it, the 2019 international guideline from EPUAP, NPIAP and the Pan Pacific alliance recommends 1.25 to 1.5 grams of protein per kilogram of body weight per day, with 30 to 35 kilocalories per kilogram per day for energy (1).

Those are the best-supported numbers in wound nutrition, and I use them as the floor for any significant open wound, not only pressure injuries. Most people are nowhere near them. A 70 kilogram adult needs roughly 88 to 105 grams of protein a day on that recommendation, and the typical intake I hear described on a video visit is half that.

Worth noting the overlap with the rest of my practice. When I start a patient on an incretin I ask for 1.6 grams per kilogram per day and strength training two to three times a week, because the risk on those drugs is lean mass loss. A patient on an incretin who also has a wound is being asked for the same thing for two different reasons, which makes the conversation easier rather than harder.

Arginine, and how good the evidence actually is

Arginine gets singled out because it is a substrate for nitric oxide and for proline, and proline goes into collagen. The 2019 guideline recommends a high-calorie, high-protein oral nutrition supplement fortified with arginine, zinc and antioxidants for adults with a stage 2 or greater pressure injury who are malnourished or at risk of malnutrition (1).

Read that recommendation carefully, because it is narrower than how it gets quoted. It is for a specific wound severity, in a specific nutritional context, and the arginine comes inside a fortified supplement rather than as arginine on its own (2). The trials behind it tested the whole formulation. Nobody has shown that arginine by itself, added to an adequate diet in a well-nourished person, does anything for a wound.

I have no objection to those supplements in the patients the guideline describes. I do object to a well-fed person with a healing surgical incision spending money on arginine capsules.

Vitamin C and zinc

Both are genuinely required for wound healing. Vitamin C is a cofactor for the hydroxylation steps in collagen synthesis, and frank scurvy produces wounds that will not close. Zinc deficiency impairs epithelialization.

None of that means supplementing someone who is not deficient helps. Reviews of vitamin and mineral supplementation in wound care keep landing in the same place: unclear benefit unless there is a confirmed or suspected deficiency, and no well-powered randomized trial showing that routine vitamin C or zinc speeds healing in replete patients (3).

So I correct documented deficiencies and I do not supplement reflexively. High-dose zinc in particular is not harmless; it interferes with copper absorption over time.

This is the part of the conversation patients like least, and I say it anyway.

What matters more than any of it

Smoking. Sørensen’s meta-analysis of surgical patients found substantially higher rates of wound complications and infection in smokers, and improvement with cessation before surgery (4). If a patient with a slow wound smokes, that is the highest-yield thing on the list, and it is not close.

Then perfusion. A wound on a limb without a decent pulse is a vascular problem wearing a dressing, and no amount of protein fixes it.

Then offloading and moisture balance, which are mechanical rather than nutritional and are where most home wound care goes wrong.

Nutrition belongs on the list. It belongs below those.

For patients

Eat more protein than you think you need while a wound is open. Aim for something in the range of 1.25 to 1.5 grams per kilogram of your body weight per day, which for most adults means adding a protein source to every meal rather than eating one large dinner. If you are diabetic, the wound is a reason to tighten control now, not later.

Skip the wound-healing supplement stack unless your clinician has found an actual deficiency. If you smoke, stopping will do more for that wound than everything else on this page combined.

For colleagues

Ask what people are eating before you reach for a supplement, and ask in grams rather than in general terms. The 1.25 to 1.5 g/kg recommendation is easy to quote and rarely translated into food for the patient, which is where it fails.

Check a zinc or vitamin C level if the history suggests deficiency, then treat what you find. Do not treat the wound with a multivitamin on principle.

And put smoking cessation at the top of the plan for any wound that is behind schedule, ahead of the dressing change conversation.

The Bottom Line

Wounds heal on protein, calories and blood flow, in something like that order, and they stall on high glucose and tobacco. The guideline numbers worth remembering are 1.25 to 1.5 grams of protein per kilogram per day and 30 to 35 kilocalories per kilogram per day. Arginine and antioxidant supplements have a real place, in malnourished patients with stage 2 or worse pressure injuries, and almost nowhere else. Vitamin C and zinc are worth correcting when they are low and worth skipping when they are not. If you fix only one thing on this list, fix the smoking.

Sources

1. European Pressure Ulcer Advisory Panel, National Pressure Injury Advisory Panel and Pan Pacific Pressure Injury Alliance. The Role of Nutrition for Pressure Injury Prevention and Healing: 2019 International Clinical Practice Guideline recommendations. https://cdn.ymaws.com/npiap.com/resource/resmgr/The_Role_of_Nutrition_for_Pr.pdf

2. Chu AS, Delmore B. Arginine: What You Need to Know for Pressure Injury Healing. Adv Skin Wound Care. 2021;34(12):630-636. PMID 34807894. https://pubmed.ncbi.nlm.nih.gov/34807894/

3. Indian Health Service National Pharmacy and Therapeutics Committee. Formulary Brief: Nutritional Supplements in Wound Healing. https://www.ihs.gov/sites/nptc/themes/responsive2017/display_objects/documents/guidance/NPTC-Formulary-Brief-NutritionalSupplementsinWoundHealing.pdf

4. Sørensen LT. Wound healing and infection in surgery. The clinical impact of smoking and smoking cessation: a systematic review and meta-analysis. Arch Surg. 2012;147(4):373-383. PMID 22508785. https://pubmed.ncbi.nlm.nih.gov/22508785/

5. Armstrong DG, Boulton AJM, Bus SA. Diabetic Foot Ulcers and Their Recurrence. N Engl J Med. 2017;376(24):2367-2375. PMID 28614678. https://www.nejm.org/doi/10.1056/NEJMra1615439

Digital scale showing weight comparison of green and purple capsules in milligrams

Foundayo vs. the Wegovy Pill: Comparing the Two New Weight Loss Pills

On July 31, 2026November 7, 2026 By Dr. Scott RennieIn Weight Loss & Metabolic HealthLeave a comment

For years, if you asked me “is there a pill version of these weight-loss drugs?”, the honest answer was no, not really. That changed twice, four months apart. If you haven’t been following closely, the options today look nothing like they did two years ago.

A quick note on names first, since patients ask me this a lot. The Lilly drug some people have heard called “Fonday-o” is orforglipron. The FDA approved it on April 1, 2026, under the brand name Foundayo (1). Before that, on December 22, 2025, the FDA approved a 25 mg oral semaglutide tablet under the Wegovy name (2). GLP-1 medicines help control appetite and blood sugar, and that tablet was the first pill version of one approved for long-term weight management. Both are real, both are approved, and both can be prescribed today.

Both full prescribing labels are now public, and they differ in ways that decide the choice for a lot of people. Most of those differences have nothing to do with how much weight each one takes off.

Why the two pills work so differently in your body

Semaglutide is a peptide, which is a small chain of amino acids, the building blocks of proteins. Your stomach is very good at breaking down peptides, which is exactly why semaglutide originally had to be given as a shot.

Novo Nordisk’s solution was to add an ingredient called SNAC that helps the drug get absorbed before your stomach destroys it. According to a review in the journal Clinical Diabetes, SNAC does three things at once (3). It changes the local acidity around the tablet as it dissolves, it briefly protects the drug from a stomach enzyme called pepsin, and it helps the drug cross the stomach lining into your bloodstream. The absorption happens in the stomach itself rather than the intestines, which is unusual for a pill. The drug essentially enters your body right where the tablet is sitting against your stomach wall.

That trick comes with a catch, and the label is specific about it (4). You take the tablet on an empty stomach in the morning with no more than four ounces of plain water. No other liquids. Swallow it whole, and wait at least 30 minutes before you eat, drink anything, or take any other oral medication.

Thirty minutes. Every morning. Before coffee.

Orforglipron works completely differently. It is a small molecule, meaning a stable chemical rather than a fragile peptide chain. It belongs to the same drug family, mimicking a natural gut hormone that reduces appetite, but with no peptide to protect it needs no absorption booster and carries no timing ritual. Its label says to take it once daily with or without food, and specifies no water restriction and no waiting period (5). For someone who works nights, or who already swallows six other pills at breakfast, that is the whole ballgame.

What the labels actually say, and why the number in your news feed is wrong

Most of the figures circulating online come from journal publications and press releases rather than from the approved labels. The label numbers are the ones your prescription is based on, so those are the ones I use.

For Wegovy tablets, the label reports a 64-week trial in 205 adults on the tablet against 102 on placebo, all with obesity or overweight plus a weight-related condition, with diabetes excluded (4). Average weight change was 13.6 percent down on the tablet and 2.4 percent down on placebo, a difference of 11.2 percentage points. Broken out by how much people lost: 76.3 percent lost at least 5 percent of their body weight versus 31.3 percent on placebo, 59.8 percent lost at least 10 percent versus 14.4 percent, 47 percent lost at least 15 percent versus 5.5 percent, and 27.9 percent lost at least 20 percent versus 3.1 percent.

For Foundayo, the label reports a 72-week trial in 3,127 adults without diabetes (5). Average weight change was 7.4 percent down at the 5.5 mg dose, 8.3 percent down at 9 mg, and 11.1 percent down at the maximum 17.2 mg dose, against 2.1 percent down on placebo. At 17.2 mg, 35.9 percent of patients lost at least 15 percent of their body weight, compared with 6 percent on placebo.

Put those side by side and the semaglutide tablet looks better, and I would be careful with that read. Different patients, different trial lengths, different placebo responses, and nobody randomized the same people to both. What is harder to wave away is the size of each evidence base. The semaglutide tablet’s label efficacy rests on 205 treated patients. Foundayo’s rests on 3,127. Both cleared the FDA, so both met the bar, but I have more confidence in how a drug behaves across a wide range of real people when the number in the trial is measured in thousands.

Here is the detail that confuses almost everyone who reads the news coverage. The approved Foundayo strengths are 0.8, 2.5, 5.5, 9, 14.5, and 17.2 mg, stepped up roughly every 30 days. The trial used a capsule at 1, 3, 6, 12, 24, and 36 mg. Those map onto each other in order, so the 17.2 mg tablet you can actually be prescribed is the 36 mg dose you read about. If your maximum dose sounds far smaller than the headline, that is why.

One thing I noticed reading the Foundayo label closely: the 14.5 mg strength is approved and dispensable, and it does not appear in the label’s efficacy table at all. You can be prescribed a dose with no published average weight loss attached to it. Not dangerous, just worth knowing if you end up parked there.

The only comparison anyone has run, and who paid for it

There is still no head-to-head trial of these two drugs in obesity. There is now an indirect comparison, published in Diabetes, Obesity and Metabolism in August 2026, which pulled individual patient data from the semaglutide tablet trial and aggregate data from the orforglipron trial and statistically adjusted for differences in sex, body weight and glucose status between the two populations (6).

It found oral semaglutide 25 mg ahead by 3.2 percentage points of body weight (95% confidence interval 5.9 to 0.4) and reported higher discontinuation with orforglipron, with an odds ratio of 4.1 for stopping due to any adverse event and 13.9 for stopping due to gastrointestinal side effects.

Five of the authors are Novo Nordisk employees and shareholders, two more work for a consultancy Novo paid to run the analysis, and Novo makes the drug that won. That does not make the result false. It does mean I apply a discount. The direction is plausible and roughly matches the gap between the two labels. The magnitude I would not quote to a patient as fact. And that gastrointestinal odds ratio of 13.9 has a confidence interval running from 2.0 to 96.0, which is another way of saying the study could not pin it down.

There is one true head-to-head, and it points the other way. In adults with type 2 diabetes, orforglipron beat oral semaglutide on weight loss (7). That trial used semaglutide at 7 mg and 14 mg, well under the 25 mg weight-management dose, in a different population, for a different purpose. It answers a different question than the one you are asking.

Birth control is the difference nobody mentions

This is the most actionable difference between the two drugs and it almost never comes up in the coverage.

The Foundayo label instructs patients on oral hormonal contraceptives to switch to a non-oral method, or to add a barrier method for 30 days after starting the drug and for 30 days after every dose escalation (5). Count the escalations. With six strengths, somebody climbing to the top dose is looking at several separate 30-day windows where their pill alone is not considered reliable. Non-oral hormonal contraception is not expected to be affected.

The Wegovy tablet label carries no equivalent instruction. Its pharmacokinetic studies found no clinically significant interaction with ethinyl estradiol and levonorgestrel (4).

For a woman in her twenties or thirties on a combined oral contraceptive who does not want a pregnancy, that single difference outweighs three percentage points of average weight loss. I bring it up before either drug gets prescribed, not after.

The other interactions that quietly decide this

Orforglipron is cleared through CYP3A4, and the label puts real fences around that (5). On a strong CYP3A4 inhibitor, the maximum Foundayo dose drops to 9 mg. Clarithromycin raised orforglipron exposure 3.5-fold in a study. Going the other way, carbamazepine cut exposure by 82 percent and efavirenz by 61 percent, so strong inducers are to be avoided and moderate ones need the dose pushed up while you watch whether it still works. Strong inhibitors that also block OATP1B, ritonavir being the example the label gives, are to be avoided outright. And simvastatin is capped at 20 mg a day alongside it.

The semaglutide tablet has a shorter list but one that matters in my practice. A single 600 mcg dose of levothyroxine taken with it produced a 33 percent rise in total thyroxine exposure (4). Add the 30-minute rule on top, which pushes every other morning medication back, and a patient on thyroid replacement plus a few other dailies has a genuine scheduling problem.

If someone comes to me on carbamazepine, or on ritonavir-boosted therapy, Foundayo is awkward enough that I start elsewhere. If someone is on levothyroxine and already struggles to take it correctly, I think hard before adding a second pill with its own empty-stomach window.

Side effects

Both drugs hit the gut, and both labels say so plainly.

Foundayo’s pooled safety data runs nausea at 26 percent, 34 percent and 35 percent across the 5.5, 9 and 17.2 mg doses against 10 percent on placebo (5). Vomiting climbs from 13 to 24 percent against 4 percent. Constipation runs 20 to 27 percent against 9 percent, and diarrhea 21 to 25 percent against 11 percent. Hair loss shows up at 4 to 5 percent against 2 percent, which patients ask me about more than the numbers would suggest.

The Wegovy tablet label describes side effects similar to the injection, and adds a few tablet-specific figures (4). Just under 7 percent of patients stopped the drug for an adverse reaction, against about 6 percent on placebo. Severe gastrointestinal reactions occurred in 2 percent of tablet patients and no placebo patients. Dysesthesia, meaning abnormal or unpleasant sensation, was reported in 5 percent of tablet patients and in nobody on placebo. That last one is not something I had on my radar before reading the label, and it is worth mentioning to a patient who calls about odd skin sensations rather than writing it off.

Both drugs carry a boxed warning about thyroid C-cell tumors and are contraindicated in anyone with a personal or family history of medullary thyroid carcinoma or MEN 2 (4)(5).

If you have heart disease, the answer is already made

Wegovy tablets carry an approved indication to reduce the risk of major adverse cardiovascular events, meaning cardiovascular death, non-fatal heart attack and non-fatal stroke, in adults with established cardiovascular disease and either obesity or overweight (4). The wording is identical to the injection’s.

Foundayo has no cardiovascular outcome indication. Its cardiovascular outcomes trial has not reported.

For a patient who has already had a heart attack or a stroke, that settles it. I go to semaglutide, and the only remaining question is tablet or injection.

How I actually choose

If you are the patient reading this, the useful question is not which drug is stronger. It is which one you will still be taking in a year. The 30-minute waiting period for the semaglutide tablet sounds minor when we talk it through on a video visit, and it trips people up in real life. I have watched patients lose ground on oral semaglutide because weekday mornings made the timing rules impossible to follow, and the drug cannot work from inside the bottle. If your mornings are chaotic, say so out loud when we talk. That is clinical information, not an excuse.

If you are a prescriber, I would frame the choice around four things before efficacy. Established cardiovascular disease points to semaglutide on the label. An oral contraceptive points away from orforglipron, or at least commits you to counseling a barrier method through every escalation. A CYP3A4 problem, especially an enzyme inducer, makes orforglipron hard to dose. Levothyroxine and a crowded morning pill box make the semaglutide tablet hard to take. What is left after those four filters is usually a clear answer, and in my experience the efficacy gap is the least useful thing to lead with.

What this costs right now

Both manufacturers run tiered self-pay pricing that starts low at the smallest dose and rises as you titrate up, and both have promotional rates on their lower strengths that are scheduled to end on December 31, 2026. Because these terms change faster than I can keep a blog post current, check the two official pages directly rather than trusting a number you read anywhere, including here: LillyDirect for Foundayo (8) and NovoCare for Wegovy (9).

What I can tell you from prescribing both is operational. I haven’t run into a prior-authorization fight or a stocking problem with Foundayo yet. Most of what I prescribe goes through LillyDirect on cash pay, because it has been one of the cheaper options on the table. Patients who have real insurance coverage tend to ask for injectable Wegovy or Zepbound instead, and I do not talk them out of it. For a fuller breakdown of cash prices across the whole class, including the injections, see my separate post on cash pay options.

The Bottom Line

Two pills, both approved, both effective, and the deciding factors are mostly not about weight loss. The semaglutide tablet takes off a bit more weight in the label data, carries a cardiovascular indication, and demands an empty stomach and a 30-minute wait every single morning. Foundayo asks nothing of your schedule, has a far larger trial behind it, and brings a contraception instruction and a list of drug interactions that rule it out for some people entirely.

Bring your actual medication list and your actual morning routine to the visit. Those two things will pick the drug faster than any comparison chart.

Sources

1. FDA approves Lilly’s Foundayo (orforglipron), the only GLP-1 pill for weight loss (Eli Lilly): https://investor.lilly.com/news-releases/news-release-details/fda-approves-lillys-foundayotm-orforglipron-only-glp-1-pill

2. FDA approves Novo Nordisk’s Wegovy pill, the first and only oral GLP-1 for weight loss in adults (PR Newswire): https://www.prnewswire.com/news-releases/fda-approves-novo-nordisks-wegovy-pill-the-first-and-only-oral-glp-1-for-weight-loss-in-adults-302648344.html

3. Current Understanding of SNAC as an Absorption Enhancer: The Oral Semaglutide Experience (Clinical Diabetes, American Diabetes Association): https://diabetesjournals.org/clinical/article/42/1/74/153538/Current-Understanding-of-Sodium-N-8-2

4. WEGOVY (semaglutide) injection and tablets, US prescribing information (DailyMed): https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=ee06186f-2aa3-4990-a760-757579d8f77b

5. FOUNDAYO (orforglipron) tablets, US prescribing information (Eli Lilly): https://uspl.lilly.com/foundayo/foundayo.html

6. Michalak W, Bøg M, Bendixen T, Chowdhury R, Cowley P, Laugesen C, et al. Oral Semaglutide 25 mg Versus Orforglipron 36 mg in Obesity: A Population-Adjusted Indirect Treatment Comparison. Diabetes, Obesity and Metabolism. 2026;28(8):7247-7256: https://pubmed.ncbi.nlm.nih.gov/42225305/

7. Orforglipron Outperforms Oral Semaglutide in Head-to-Head Type 2 Diabetes Trial (AJMC): https://www.ajmc.com/view/orforglipron-outperforms-oral-semaglutide-in-head-to-head-type-2-diabetes-trial

8. Foundayo self-pay pricing (LillyDirect): https://www.lilly.com/lillydirect/foundayo

9. Wegovy self-pay pricing (NovoCare): https://www.novocare.com/

10. Orforglipron, an Oral Small-Molecule GLP-1 Receptor Agonist for Obesity Treatment (New England Journal of Medicine, ATTAIN-1): https://www.nejm.org/doi/full/10.1056/NEJMoa2511774

Vegetables and fruit beside a bathroom scale and a tape measure

Is Yo-Yo Dieting Bad for You? Weight Cycling Explained

On May 10, 2025September 29, 2026 By Dr. Scott RennieIn Weight Loss & Metabolic HealthLeave a comment

A lot of my patients describe the same arc. They work hard, lose weight, feel good for a while, and then months or years later it comes back. That repeated loss and regain is weight cycling. It is common, and it is hard on people both physically and emotionally.

The question I hear most often is whether it is even worth trying if the weight is coming back anyway. The research answers that more clearly than it used to, and the answer is yes.

Weight cycling generally means repeated intentional loss followed by unintentional regain. Some researchers set the bar at a 10 percent change in body weight occurring three or more times. Depending on the study, it affects 20 to 35 percent of men and up to half of women (Montani et al., 2015).

Why does the weight return? Biology pushes back harder than most people anticipate. After weight loss, resting energy expenditure falls further than body size alone would predict, and this metabolic adaptation can persist for years, meaning the body burns less than expected (Fothergill et al., 2016). Hormones move too. Leptin drops, hunger hormones climb, and patients end up hungrier and less satisfied by meals than they were before (Sumithran et al., 2011). The body also tends to compensate for exercise by raising appetite. Together these explain why maintenance is the hard part, not the losing (Thomas et al., 2012).

The real question is whether the cycling itself does damage. Large reviews and cohort studies have not found strong evidence that weight cycling raises mortality or major chronic disease risk when the weight loss is intentional and supervised (Mehta et al., 2014). Some work suggests regain may favor fat over muscle, visceral fat especially, though the findings are inconsistent (Mackie et al., 2017).

The psychological picture is better than most people assume. Foster and colleagues found that patients who regained weight still reported improvements in mood, hunger, and eating behavior after the loss phase (Foster et al., 1996). Other work has found no consistent long-term harm from the pattern itself (Osborn et al., 2011).

So should patients keep trying? The National Task Force on the Prevention and Treatment of Obesity concluded in 1994 that weight cycling should not deter people from attempting weight loss, and that position has held up (National Task Force, JAMA 1994). The benefits of intentional loss, lower blood pressure, better lipids, better glucose control, better quality of life, generally outweigh the risk of regaining.

One of my patients lost about 8 percent of her body weight through diet and walking. A year later most of it had come back. During the stretch she kept it off, though, her blood pressure normalized and she came off one of her antihypertensives. The weight returned. The benefit she got during that window was real and measurable, and the research says her experience is the rule rather than the exception.

What I steer patients toward is sustainable habit rather than another aggressive diet. Regular activity, consistent eating patterns, decent sleep, and watching the trend line instead of the daily number. A setback does not undo the progress. Staying connected to support, whether that is a clinician, a dietitian, or counseling, matters more than most people expect.

Weight cycling is real and it is discouraging. It is not a reason to stop. Even temporary weight loss buys real health, and the useful reframe is to treat weight management as ongoing care rather than a project with an end date.

Does Fasting Slow Aging? What the Science Says

On May 4, 2025September 11, 2026 By Dr. Scott RennieIn Longevity & Healthy AgingLeave a comment

Aging cannot be stopped. The pace of it may be influenced by what and when we eat, and that idea is old rather than new. Since the 1930s, animal studies have shown that cutting calories without causing malnutrition extends lifespan. Rodents held at a 30 percent reduction lived longer with less cancer and less heart disease.

The proposed mechanisms are lower oxidative stress, better mitochondrial function, and less inflammation. Less fuel in, less metabolic wear.

Then you move from mice to people and it gets complicated.

The CALERIE trials brought calorie restriction into human research. CALERIE II found that cutting roughly 15 percent of calories for two years improved blood pressure, cholesterol, and markers of oxidative stress, and those benefits appeared without major weight loss (Kraus et al., 2019). The obstacle is adherence. Sustained restriction is hard on mood, on social life, and on nutritional balance, and most people will not hold it.

Which is how fasting patterns entered the conversation. Intermittent fasting covers several approaches. Some people fast on alternate days. Others follow 5:2, eating normally five days a week and restricting on two. Time-restricted feeding, which confines eating to an 8 to 10 hour window, has drawn the most recent attention.

Alternate-day fasting does produce fat and weight loss, but hunger is a serious barrier and dropout rates run high. Modified versions have not clearly outperformed standard calorie restriction (Trepanowski et al., 2017).

Time-restricted feeding looks more workable. Sutton and colleagues tested an early schedule with all meals between 7 a.m. and 3 p.m. Participants did not lose weight, but insulin sensitivity, blood pressure, and oxidative stress markers all improved, and they reported less hunger through the evening (Sutton et al., 2018). Other short-term work points the same direction, particularly on appetite control and metabolic flexibility (Hatori et al., 2012; Varady et al., 2022).

What does that mean in practice? Calorie restriction has the strongest animal data and some genuinely promising human results, and almost nobody sustains it. Alternate-day fasting rarely survives contact with real life. Time-restricted feeding is the one most patients can actually keep, and even moving to a 10 hour window and dropping late-night meals is a defensible starting point.

When I talk this through with patients, I usually suggest starting at a 12 hour window and tightening it only if they tolerate the change well. What goes in the window still matters more than the window does, and nutrient density should not get lost in the enthusiasm about timing.

Fasting is one tool among several, and which one fits depends on the person, their health, and what they can hold onto for longer than a month.

Do Weight Loss Supplements Work? What Research Shows

On April 27, 2025September 11, 2026 By Dr. Scott RennieIn Weight Loss & Metabolic HealthLeave a comment

Patients ask me about supplements constantly. They have seen an ad promising fast results from something natural and want to know whether it is worth a try. The answer is duller than the advertising. The evidence behind most weight loss supplements is thin, and the safety problems are not.

Paul R. Thomas at Columbia University’s Institute of Human Nutrition has reviewed this literature. What he and others find is that these products mostly do not work. The studies that exist tend to be small, short, and funded by the companies selling the product. Where a benefit shows up, it is small. Garcinia cambogia came in at under a kilogram of difference against placebo. That is not what patients are hoping for when they buy it, and it is not remotely close to what lifestyle change or an FDA-approved medication will do (Thomas, 2022).

The marketing claims sort into a few categories. Appetite suppression is credited to hoodia, glucomannan, and saffron. Metabolic or energy boosting gets attributed to caffeine, green tea extract, and bitter orange. Fat absorption blocking is the pitch for chitosan, and reduced fat synthesis for CLA and garcinia cambogia. The proposed mechanisms sound reasonable. The measured effects are close to nothing.

Safety is the more serious issue. Supplements do not have to be proven safe or effective before they are sold, because they are regulated closer to food than to drugs. The FDA can generally act only after harm is documented, which leaves a wide window. Independent testing has repeatedly turned up quality failures, including heavy metal contamination and doses that do not match the label. Some products have been found to contain banned or genuinely dangerous drugs, among them sibutramine, pulled from the market over cardiovascular risk, and phenolphthalein, a carcinogen (Tucker et al., 2018).

The harm is documented rather than theoretical. Roughly 23,000 emergency department visits a year in the United States are attributed to supplements, and weight loss and energy products account for most of them. The usual presentations are palpitations, chest pain, and tachycardia, and the patients are disproportionately young adults in their twenties and early thirties (Geller et al., 2015).

When patients ask what to do, I tell them to be careful. If they are going to use something, single-ingredient products from established national brands are the safer end of the pool, ideally with third-party verification such as USP or NSF. Avoid proprietary blends that will not disclose what is in them. Be suspicious of anything promising to melt fat. If they have a reaction, stop the product, keep the bottle, and report it to Poison Control and the FDA’s MedWatch program.

Supplements are everywhere and the evidence does not support them. Nutrition, physical activity, behavioral support, and where appropriate FDA-approved medication remain both more effective and considerably safer than whatever is currently being advertised.

Do Weight Loss Apps and Devices Really Help?

On April 26, 2025September 29, 2026 By Dr. Scott RennieIn Weight Loss & Metabolic HealthLeave a comment

Patients ask me whether weight loss apps and digital programs actually work. It is a fair question, and the honest answer has a lot of qualifiers in it. Traditional obesity care runs into limited visit time, cost, and a shortage of places to refer people. Technology, whether an app, a web platform, or a hybrid program with human coaching, routes around some of that.

Dr. Bonnie Spring at Northwestern has studied how eHealth, mHealth, and telehealth are reshaping obesity treatment. Her finding is that these tools extend reach, lower cost, and deliver feedback in real time. The difficulty is holding anyone’s attention long enough for that to matter.

The trends in the research are reasonably clear. Web-based programs on their own produce small losses, around 2 to 3 percent of body weight. Better than nothing, and well short of the 7 to 8 percent that structured in-person programs achieve (Wieland 2014; Raaijmakers 2015; Tang 2014). Roughly half of users drop out.

Mobile approaches do better. In a review of U.S. trials, about 63 percent of studies found meaningful weight loss with mHealth interventions (Burke, Ma, Spring 2015). Texting on its own moved very little; outcomes improved when coaching or app-based monitoring was layered on. The catch is that most people abandon apps almost immediately, with more than three quarters stopping within three days of downloading.

Spring’s Opt-In Study used the Multiphase Optimization Strategy to build something cost-effective: remote sessions, structured self-monitoring, goal setting, and a trained buddy for support. Participants targeted a 7 percent loss, the threshold known to reduce diabetes and cardiovascular risk. More than half got there, at under $500 per person. That is comparable to the Diabetes Prevention Program at a fraction of the cost.

The buddy component turned out to matter most. Having a friend or family member reinforcing the changes between formal sessions kept people going, which lines up with what we already knew: social support is among the strongest predictors of durable results.

Access remains uneven. Reliable internet and comfort with digital tools are not evenly distributed, even though weight loss apps are among the most downloaded health apps in the world (Nikolaou & Lean, 2017). Owning a smartphone is the easy part. Cultural fit, affordability, and whether someone finds the technology tolerable all matter as much.

In my practice I have seen patients do well with commercial programs like Omada or Noom, which pair app-based tracking with remote coaching. Others get further with something simpler, MyFitnessPal being the usual example. These run somewhere between $40 and $130 a month, which is its own barrier and worth asking about before recommending one.

Technology works when it carries evidence-based strategy inside it: goal setting, self-monitoring, timely feedback, social support. Without those it is a download that gets deleted on day three. Knowing which products have research behind them and which have marketing behind them is part of our job now, and steering a patient toward the right one is often what separates a few weeks of enthusiasm from an actual result.

Does Chronic Stress Cause Weight Gain? A Doctor Explains

On April 25, 2025September 11, 2026 By Dr. Scott RennieIn Weight Loss & Metabolic HealthLeave a comment

Obesity gets described as a balance of diet and exercise, and stress plays a far larger role in it than most people are told. I have seen patients who eat well and stay active and still lose ground the moment their stress rises. Research from Dr. Rajita Sinha at Yale explains a good deal of why. Chronic stress produces measurable biological change, well past anything you would call a mood.

Stress acts on the brain circuits governing emotion, motivation, and self-control. Those circuits overlap with the ones handling food reward and craving, particularly for calorie-dense processed food (Sinha et al., 2022). Cortisol climbs under chronic stress. Ghrelin rises with it while leptin falls. What you end up with is a body primed to eat more, in an environment where high-calorie food is always within reach.

Calling that emotional eating undersells it. In Sinha’s lab work, people exposed to stress through guided imagery ate more snack food afterward, and participants who were already overweight were the most affected. Their cravings and calorie intake tracked with measured increases in cortisol and ghrelin. The stress reached past how they felt and changed how their brains and bodies handled food.

The pandemic ran this experiment at national scale. Nearly half of U.S. adults gained weight over that period, with worse effects among people who already had higher BMIs (Khubchandani et al., 2022). Children were not spared; CDC data showed the rate of BMI increase doubling against pre-pandemic years (Lange et al., 2021). The predictors of gain were emotional distress, having children at home, and how long it had been since someone last weighed themselves.

Work outside the pandemic points the same way. In one community study, people with higher baseline cortisol and greater insulin resistance were more likely to gain weight over the following six months (Chao et al., 2017). Those markers did more than correlate with obesity. They predicted it.

That has pushed researchers past the eat-less-move-more framing toward treatments aimed at the stress itself. Mindfulness-based stress reduction lowers food cravings, perceived stress, and blood pressure in people with obesity (Tuit et al., 2011). There is even evidence in parenting: a small study of low-income mothers found mindful parenting reduced parental stress and was associated with healthier BMI outcomes in their children (Jastreboff et al., 2018).

Medical and surgical treatment still matter, and the evidence suggests they perform best alongside strategies that reduce stress reactivity and support executive function. Stress management belongs in the treatment plan rather than tacked onto the end of it.

I have seen patients who feel defeated because they are certain the weight they gained under stress was a personal failure. The science says otherwise. Stress reshapes brain pathways, moves hormone levels, and changes eating behavior in ways we can measure. None of that makes change impossible. It does mean compassion is not optional in this conversation, and that treating stress as part of the disease moves the discussion off blame and onto something we can actually act on.

How Weight Stigma Hurts Health and Makes Obesity Worse

On April 20, 2025September 29, 2026 By Dr. Scott RennieIn Weight Loss & Metabolic HealthLeave a comment

Conversations about obesity circle back to calories, exercise, and willpower almost every time. Weight stigma gets far less airtime and carries comparable weight. I have seen patients delay care or stop coming back entirely because of how they were treated somewhere else. The discomfort is the smaller part of it. The evidence says stigma itself worsens health and can contribute to weight gain.

Weight stigma is being stereotyped or discriminated against because of body size. It shows up in schools, workplaces, public spaces, and clinical settings. Dr. A. Janet Tomiyama’s work frames it as a chronic stressor, and stress is never metabolically neutral. It sets off hormonal changes that drive appetite and shift metabolism.

Her team built the COBWEBS model to describe the loop. Stigma triggers stress, cortisol rises, cravings intensify, calorie-dense food becomes more appealing, weight gain follows, and the weight gain brings more stigma (Tomiyama, 2014).

The measurements back the model. Women with higher BMIs who reported more stigma experiences had significantly higher morning cortisol than women at similar BMIs reporting fewer such experiences (Tomiyama et al., 2014). What separated the two groups was not their weight. It was how they had been treated.

Simulated experience shows it too. Participants who wore a fat suit to approximate living in a larger body reported more distress afterward and ate more calorie-dense snacks than controls (Heldreth et al., 2018). The premise that shaming people improves their health does not survive contact with the data. It usually produces the opposite.

The longitudinal picture is worse. Adolescent girls teased about their weight by family or peers had higher BMIs years later, holding self-esteem and body image constant (Hunger & Tomiyama, 2014). Stigma sits upstream of obesity as well as downstream. It forecasts it.

Healthcare has no exemption here. Clinicians who specialize in obesity medicine have been shown to carry implicit anti-fat bias, and patients pick up on it immediately. I have had patients tell me directly that they put off care because they did not want to be weighed or judged again. The literature matches what they describe: stigma in healthcare settings is associated with shorter visits, fewer diagnostic tests, and worse outcomes (Tomiyama et al., 2022).

It reaches providers as well. Medical students who internalize anti-fat bias have higher rates of depression and substance use. The damage runs in more than one direction.

Weight stigma is a health risk in its own right. It raises stress, fuels craving, keeps people away from care, and pushes outcomes the wrong way. What patients need is care aimed at behavior and health rather than at their size, and the work for us is examining our own language, our assumptions, and the spaces we ask people to walk into.

Can Diet and Exercise Lower Cancer Risk in Obesity?

On April 20, 2025September 11, 2026 By Dr. Scott RennieIn Weight Loss & Metabolic HealthLeave a comment

When obesity comes up, the conversation goes to diabetes, heart disease, and joints. Cancer rarely makes the list, and it belongs near the top of it. Obesity is an established risk factor for developing several cancers and for dying from them. Over the past twenty years the evidence has firmed up considerably that lifestyle change, cutting calories and adding endurance exercise in particular, lowers that risk and improves outcomes for patients already diagnosed.

The biology is messy and worth understanding anyway. Surplus calories expand fat tissue, and enlarged fat cells are metabolically active rather than inert. They drive systemic inflammation, disrupt insulin signaling, and shift leptin, insulin, and estrogen levels. The resulting environment is one cancer establishes itself in more easily. Longo and Fontana described how obesity suppresses protective factors like adiponectin and sex hormone-binding globulin while raising free fatty acids, inflammatory cytokines, and oxidative stress (Longo & Fontana, Trends Pharmacol Sci, 2010). That combination degrades DNA repair, lets mutated cells survive, and weakens immune surveillance.

The clinical consequences follow. Patients with obesity are more likely to develop breast and endometrial cancer, both hormone-sensitive. Insulin and IGF-1 push cells to keep dividing. Suppressed SHBG leaves more free estrogen circulating. Chronic inflammation supplies the rest. Tumors appear in that setting and then do well in it.

Caloric restriction has decades of animal work behind it. Rodents held at roughly 30 percent fewer calories lived longer with fewer tumors (Weindruch & Sohal, NEJM, 1997; Masoro, Mech Ageing Dev, 2005). Non-human primates showed the same pattern, and in one study moderate restriction halved cardiovascular and cancer deaths (Colman et al., Science, 2009). Human trials are shorter but pointed in the same direction: a two-year study cutting intake 13 percent improved insulin sensitivity, lowered fasting insulin, and reduced oxidative stress (Kraus et al., Lancet Diabetes Endocrinol, 2019).

Exercise moves the same levers by a different route. Endurance training improves glucose uptake in muscle through increased GLUT4 expression, trims visceral fat, and lowers fasting insulin. A year-long trial in middle-aged adults found regular endurance exercise reduced weight, visceral fat, and insulin (Weiss et al., Am J Clin Nutr, 2006). A single session improves insulin sensitivity temporarily, and the benefit is gone in about ten days without activity (McCoy et al., J Appl Physiol, 1994). That is the detail I bring up with patients who train hard for a month and then stop. Exercise also supports mitochondrial function and immune defense, both relevant to prevention.

Combined, the two do more than either alone. Look AHEAD followed adults with type 2 diabetes for over a decade and found 16 percent fewer obesity-related cancers among those who lost weight through lifestyle change (Look AHEAD Research Group, Obesity, 2020). Bariatric surgery, which is caloric restriction enforced surgically, halved cancer deaths in patients with obesity, most notably in women with insulin resistance (Adams et al., NEJM, 2007; Anveden et al., Gynecol Oncol, 2017).

Newer work is looking at protein and amino acid restriction. Limiting branched-chain amino acids slows tumor growth in animals, probably through mTOR signaling and immune effects (Fontana et al., Oncotarget, 2013; Orillion et al., Clin Cancer Res, 2018). Early days, but it may become another tool.

For patients the practical version is short. Modest calorie reduction and structured endurance exercise reverse a good many of the pathways connecting obesity to cancer. Around 13 percent calorie reduction looks safe and effective in human trials. For exercise, 150 to 300 minutes a week scaled to what someone can actually manage is a reasonable target. For clinicians, these belong in the core toolkit for prevention and survivorship rather than in the section of the plan we get to if there is time.

How Obesity and Nutrition Affect Cancer Risk

On April 20, 2025September 11, 2026 By Dr. Scott RennieIn Weight Loss & Metabolic HealthLeave a comment

Nutrition tends to get treated as background noise in oncology, good for general health but peripheral to the actual treatment. That view is losing ground. Food behaves as information as much as fuel, shaping metabolism, influencing tumor biology, and affecting both cancer risk and outcomes.

Obesity is the clearest illustration. It is a metabolic state rather than a matter of extra weight. Higher BMI is linked to increased incidence and mortality across several cancers, breast, colon, and endometrial among them (Calle et al., NEJM, 2003). Excess adipose tissue alters hormones, raises inflammation, and activates growth pathways that hand tumors an advantage. Elevated insulin and IGF-1 drive proliferation. Leptin rises, adiponectin falls, and the balance tips toward growth. Adipose tissue also produces estrogen, which raises risk for the hormone-sensitive cancers (Schvartzman, 2023).

Cancer cell metabolism adds a layer. Rather than relying mainly on oxidative phosphorylation, many cancer cells run aerobic glycolysis, the Warburg effect, generating both energy and the building blocks for rapid division (PMID: 26232225). Which raises the obvious question of whether diet can be used to push back.

The evidence is mixed and growing. Ketogenic diets have shown potential for boosting immune responses against tumors (PMID: 27178315), while in renal cell carcinoma and BRAF-mutated melanoma they may promote growth instead (PMID: 28089569). Restricting amino acids such as methionine, or serine and glycine, slows tumor growth in preclinical work (PMID: 28425994, 32413275). High-dose vitamin C has shown promise in KRAS-mutant cancers (PMID: 26541605). And the gut microbiota, which diet shapes, appears to affect how well patients respond to immune checkpoint inhibitors (PMID: 29097494).

All of which points toward precision nutrition. What helps one cancer may do nothing for another, or worse. Tumor type, genetics, insulin sensitivity, concurrent treatment, and the microbiome all bear on it. So does whether a patient can actually live with the diet, because one that works in theory and not in practice has not helped anyone.

So what do I tell patients? Not to follow a cancer diet, because there is no such thing. I point them toward the findings that hold up consistently. Mediterranean-style eating and lower-carbohydrate patterns reduce inflammation and may lower recurrence risk (PMID: 28935150). Fiber supports the microbiome and helps hold metabolic balance (PMID: 29098294). Observational work links nuts, fish, olive oil, and coffee to lower cancer risk or mortality (PMID: 27436272, 29158191).

One patient I worked with had breast cancer and wanted to eat better without overhauling her life. We stayed with Mediterranean-style adjustments: more vegetables, legumes, fish, and olive oil, less in the way of processed food and added sugar. Her oncologist was on board. Through treatment she held her weight steady, had fewer energy crashes, and tolerated therapy better than she expected. None of that cured anything. It was a concrete thing she could do that supported the care she was getting, and it mattered to her that it was hers to do.

Obesity and nutrition influence cancer biology directly, through metabolic and inflammatory pathways we can measure. Nutrition is not a replacement for standard therapy and it should not be the last thing we get to either.

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