DeSimone Functional Medicine

09/01/2026

A WashU randomized trial in Cell Metabolism (Petersen, Klein, and colleagues) compared ketogenic, Mediterranean, and very-low-fat plant-forward diets after matched 10% weight loss in metabolically unhealthy obesity. Obesity plus prediabetes plus hepatic steatosis. All food provided. Adherence greater than 95%. Forty-two completers, 14 per group.

• Muscle insulin sensitivity rose about 50% on all three diets. No difference, p = 0.617
• Hepatic insulin sensitivity increased two- to three-fold more on keto, p < 0.001
• MRI liver fat: keto 19.4% to 6.2% (about -67%); Mediterranean 18.1% to 10.3%; very-low-fat 17.7% to 9.6% (about -45% on both higher-carb diets)
• HbA1c: 5.6 to 5.0 on keto, 5.4 to 5.3 on Mediterranean, 5.7 to 5.3 on very-low-fat
• Fasting triglycerides fell more on keto. LDL-C, ApoB, and 24-hour triglycerides did not differ among groups
• Beta-hydroxybutyrate rose more than 20-fold on keto. No serious adverse events. No withdrawals for adverse events

Packed-out meals and a small n. Specific phenotype. Weight loss still moved muscle insulin sensitivity on every diet. The liver numbers moved more on keto.

Open-access paper: https://doi.org/10.1016/j.cmet.2026.07.020

For further information, read my blog on my website: https://desimonefm.com/same-10-weight-loss-the-liver-still-saw-a-diet-effect/

Educational only. Not a treatment plan for your case.

Same 10% down on three diets. Muscle insulin sensitivity rose about 50% on keto, Mediterranean, and very-low-fat. Liver fat and hepatic insulin sensitivity did not. Petersen, Klein, and colleagues at […]

09/01/2026

Coffee is not just caffeine.

A 2026 Journal of Translational Medicine review (Jiang and Ding) treats coffee as a mix: chlorogenic acids, trigonelline, diterpenes, melanoidins, plus caffeine. Those pieces land on mitochondrial pathways (AMPK, sirtuins, Nrf2, mitophagy). The authors call it a hypothesis, not proof.

What is usable now:
• Observational sweet spot is about 3 to 5 cups a day, not 8
• Paper filters strip most of the diterpenes that raise LDL. French press does not
• Slow CYP1A2 metabolizers keep caffeine longer. More than 2 to 3 cups may not be neutral for blood pressure or heart risk in that group
• Sugar and syrups blunt the association. Black coffee is the version in the better data
• Pregnancy: keep caffeine at or under 200 mg a day

This is not a mitochondrial miracle drink. It is a dietary pattern with a real chemistry, real limits, and real individual variation.

Open-access paper: https://doi.org/10.1186/s12967-026-08662-5

Educational only. Not a treatment plan for your case.

Background Coffee is one of the most widely consumed beverages worldwide, yet its biological effects have often been attributed primarily to caffeine. Emerging evidence suggests that coffee contains a complex array of bioactive compounds, including chlorogenic acids, trigonelline, diterpenes, and me...

08/26/2026

Your skeletal muscle and your heart age through the same biology.

A 2025 JACC Advances review (Kalra et al.) lays it out: mitochondrial dysfunction, chronic low-grade inflammation, anabolic resistance, and hormonal decline hit both tissues at once. That is why sarcopenia and a stiff, aging heart so often show up together.

Muscle mass starts falling around 50, about 1% to 2% per year. After 60 it can accelerate. Walking helps. It does not replace progressive resistance training.

What the evidence actually supports:
• Resistance work 2 to 3 times a week, plus aerobic and balance training
• Protein in the 1.0 to 1.5 g/kg/day range for most older adults (kidney disease is a different conversation)
• Vitamin D if you are deficient, testosterone if hypogonadism is real. Not as a stack for everyone
• No FDA-approved drug for sarcopenia. Pills are not the plan.

Grip strength and sit-to-stand are vital signs. Treat muscle like cardiovascular tissue, because it is.

Open-access paper: https://doi.org/10.1016/j.jacadv.2025.102347

Educational only. Not a treatment plan for your case.

08/23/2026

The brain uses about 20% of the body’s energy. In Alzheimer’s, it often can’t use glucose well. That energy failure starts early.

A 2026 review in Frontiers in Nutrition looked at intermittent fasting as a way to give the brain another fuel: ketones, especially β-hydroxybutyrate.

In animals, fasting also turns up cellular cleanup (autophagy), calms brain inflammation, and raises BDNF. In people, the picture is more cautious. Some older adults with insulin resistance improved memory on 5:2 fasting without a change in spinal-fluid Alzheimer’s markers. A longer study in mild cognitive impairment saw better cognition with regular fasting. Other trials helped metabolism more than memory.

Fasting is a tool, not a cure, and it is not safe for everyone, especially older adults at risk for muscle loss.

Full write-up: https://desimonefm.com/when-the-brain-cant-run-on-sugar-can-fasting-help-it-switch-fuels/
Paper: https://doi.org/10.3389/fnut.2026.1839995

08/22/2026

A new study shows how epigenetic aging clocks respond to longevity-promoting interventions. The paper examines whether epigenetic clocks actually shift when you try to slow aging.

https://www.nature.com/articles/s41591-026-04562-9

The study shows:

Pharmacological interventions (anti-TNF, metformin, semaglutide, etc.) produce the largest and most consistent drops.

Lifestyle (especially Mediterranean-style diets) is next. Supplements and most procedures are weaker and more mixed.

Effects are bigger in people who already have disease than in healthy volunteers.

The top interventions are:

07/24/2026

Coffee, Caffeine & Your Heart: What Does the Latest AHA Statement Say?

Good news for coffee lovers! The American Heart Association (AHA) released a comprehensive Scientific Statement on caffeine and cardiovascular disease. Here is what the latest science shows about your daily brew:

The Good News
Moderate Intake is Safe & Protective: Drinking 3–5 cups of coffee per day (up to 400 mg of caffeine) is safe for most adults and is associated with a lower risk of key cardiovascular issues, including:
Heart failure
Coronary artery disease
Stroke
Type 2 diabetes
Atrial Fibrillation (AFib): Contrary to old myths, regular caffeinated coffee consumption is associated with a lower risk of developing AFib.

The Nuances (Context Matters!)
Filtered vs. Unfiltered: Unfiltered coffee (such as French press, espresso, or Turkish coffee) contains cafestol, a compound that can raise LDL ("bad") cholesterol. Paper-filtered coffee traps cafestol, leaving your cholesterol levels unaffected!

Short-Term vs. Long-Term:
While caffeine can cause small, temporary increases in blood pressure or heart rate, long-term moderate intake is generally neutral or beneficial for overall blood pressure.

Heart Rhythm Extra Beats: Controlled trials show caffeine might slightly increase premature ventricular contractions (PVCs/extra heartbeats) in some individuals, even though it lowers overall AFib risk.

The Warnings
Energy Drinks & High Doses: The benefits of natural, brewed coffee or tea do not apply to energy drinks or high-dose synthetic caffeine powders or supplements. High concentrations (especially when paired with additives like taurine) can cause significant blood pressure spikes and cardiac harm.

Watch the Additives: Loaded coffees, packed with heavy syrups, creams, and sugars, counteract the natural health benefits of coffee.

The Takeaway
Habitual, moderate coffee drinking can comfortably fit into a healthy lifestyle! Just keep an eye on how much sugar you add, stick mostly to paper-filtered coffee if you're managing cholesterol, and skip high-dose energy drinks.

Source: Caffeine and Cardiovascular Disease: A Scientific Statement From the American Heart Association (Circulation, 2026)

07/24/2026

Turning Back the Clock on Protein Damage!
Can we reverse molecular aging? For years, scientists believed that certain age-related protein damage was permanent. A groundbreaking new study published in Nature Communications suggests we might finally be able to repair it.
The Problem: "Chemical Aging"
As we age, sugars and reactive molecules react non-enzymatically with long-lived proteins in our bodies (such as collagen in skin and blood vessels). This creates permanent damage known as Advanced Glycation End Products (AGEs).
One of the most common and damaging AGEs is CML (N^ϵ-carboxymethyl-lysine).
The impact: CML stiffens tissues, disrupts normal protein function, and triggers chronic inflammation and oxidative stress.
The challenge: Until now, CML damage was considered completely irreversible once formed.
The Solution: Engineering "CMLase"
Researchers at Revel Pharmaceuticals, Calico Life Sciences, and the University of Colorado engineered a novel enzyme, CMLase, through directed evolution (screening more than 500 million variants!).
CMLase acts like a precision molecular tool: it specifically targets and clips away the CML modification, restoring the protein to its native, healthy state.
Key Highlights & Results
Works across diverse proteins: In laboratory testing, CMLase successfully removed CML damage from key structural and transport proteins, including collagen, hemoglobin, casein, and eye extracts.
Repairs aged human tissues:
Aged Lens: Reduced CML content in human lens proteins from a 64-year-old donor by up to 78%.
Arterial Walls: Cleared over 70% of accumulated CML from 75-year-old donor human arterial tissue.
Skin: Reduced CML levels in elderly human skin by over 55%, lowering them below those found in 31-year-old tissue!
Why This Matters
This study offers crucial proof-of-concept: molecular damage once thought to be a permanent hallmark of aging can be actively erased and repaired by engineered enzymes.
While more research is needed to assess tissue pe*******on and clinical safety in living models, CMLase paves the way for an entirely new class of regenerative therapeutics targeting age-related and diabetic complications.
Paper Title: Reversal of protein chemical aging by enzymatic deglycation
Journal: Nature Communications (2026)

03/28/2026

New research in Nature Genetics just dropped the most detailed map ever of how our "biological clocks"—leukocyte telomere length (LTL)—vary across the US!

https://doi.org/10.1038/s41588-026-02567-1

Geography Matters: Significantly longer telomeres were found in the West Coast and Central Midwest, while shorter telomeres clustered in the Southeast.

Health Links: Shorter telomeres were linked to higher risks of hypertension, diabetes, and heart failure, while longer telomeres showed associations with certain neoplasms.

This study highlights that biological aging isn't just about the years—it’s a complex mix of your DNA, your s*x, and even your ZIP code.

At DFM, we will continue to evaluate patients' hsCRP for inflammatory burden, fasting insulin for metabolic health, and a CBC to assess their white blood cell population.

Analyses of leukocyte telomere length in All of Us identify associations with various lifestyle, socioeconomic and disease traits. Genome-wide analyses combining All of Us with UK Biobank data discover new loci contributing to telomere length variation.

03/19/2026

Can a Ketogenic Diet Lower Lipoprotein(a)?

Lipoprotein(a), or Lp(a), has long been considered a "genetically determined" cardiovascular risk factor that remains stable throughout a person's life. However, a striking new $n=1$ study published in BMJ Nutrition, Prevention & Health suggests we might have more control than we thought.

The Experiment:
A 55-year-old physician with a history of very high Lp(a) (peaking at 108 mg/dL) switched to a very-low-carb ketogenic diet (VLCKD).

The Results:
On Keto: His Lp(a) levels dropped significantly to 65–70 mg/dL.

The Reversal:
When he switched back to a high-carb diet for 2 weeks, his Lp(a) spiked back up to 101 mg/dL.

The Return:
After returning to the ketogenic diet for 3 weeks, his levels dropped again to 74 mg/dL.

Why it matters:
High Lp(a) affects roughly 20-30% of the population and is a major risk factor for heart disease. While this is a single-case study, it opens the door to further research on how dietary carbohydrate intake might influence this "unchangeable" genetic marker.

https://pmc.ncbi.nlm.nih.gov/articles/PMC7841845/

The level of lipoprotein(a) (Lp(a)), an important cardiovascular risk factor, is considered to be genetically determined. I am a 55-year-old male physician specialised in preventive medicine and a hobby triathlete with a body mass index of ...

01/25/2026

The "Aspirin Conundrum" Solved: Is a Daily Pill Right for You?

For years, the medical community has debated whether daily low-dose aspirin is a "life-saver" or a "risk factor" for primary prevention of heart disease. While it can prevent heart attacks, it also carries a significant risk of serious internal bleeding.

At DeSimone Functional Medicine, we don’t believe in "one-size-fits-all" medicine. A new study published in the American Journal of Preventive Cardiology suggests that the answer to the aspirin question may be found in your DNA—specifically the LP(a) gene.

The Precision Medicine Advantage:

• The Genetic Marker: A specific variant (rs3798220) in the LP(a) gene can increase your baseline risk of heart disease by more than two-fold.
• The Discovery: For those who carry this variant, daily low-dose aspirin is highly effective, reducing their elevated risk back to the level of a person without the variant.
• The "NNT" Difference: In patients with this gene, the "Number Needed to Treat" (NNT) to prevent one major event is as low as 34—making it as effective as many high-powered cholesterol-lowering medications.
• The Decision: For those without the gene, the benefits are much smaller, and the risk of bleeding may outweigh the potential reward.

One Test, One Lifetime. This simple genetic test costs roughly $25–$50 and needs to be performed only once in your life to provide lifelong clarity. It is an essential tool for identifying root-cause risks and moving beyond reactive care.

Are you taking aspirin? Let’s make sure it’s actually working for you.

(a)