Centro Fisioterapia e Osteopatia Martinelli Gianluca

23/04/2026

Vitamin C inhibits ferro-aging!

Oxidative stress may lead to aging but the mechanism is not well understood.

The researchers in this study identify that an iron-triggered aging pathway. They demonstrate that in humans and non-human primates, iron accumulation in aging fueled by chronic lipid peroxidation orchestrated via acyl-coenzyme A (CoA) synthetase long-chain family member 4 (ACSL4) and promotes cellular senescence and systemic functional decline.

The authors show that vitamin C directly targets and inhibits ACSL4, thereby blocking ferro-aging.

Their further research shows that long-term VC supplementation in in aged monkeys for over 40 months systemically attenuates aging and improves metabolic and neurological function.

https://www.cell.com/cell-metabolism/fulltext/S1550-4131(26)00053-7
https://sciencemission.com/Vitamin-C-inhibits-ACSL4

22/04/2026

Ultra-processed food consumption in childhood is only associated with early adulthood obesity among children more genetically predisposed to higher BMI, finds a study published in BMC Medicine.

Link in the comments.

19/04/2026

Stress doesn’t just affect how you feel… it literally reshapes your brain and body over time. New research shows that chronic stress leaves biological “footprints” through epigenetic changes, altering how genes are expressed and how brain circuits function long-term.

Even more striking: higher allostatic load (the wear and tear from repeated stress) is now linked to accelerated brain aging, especially in white matter networks.

And the latest 2026 findings highlight something hopeful: improving environments and behaviors can boost neurogenesis (via BDNF) and help the brain recover from stress overload. I discuss all this here: https://www.patreon.com/betterbrain

Reference: Feng L et al. (2024)

19/04/2026

Most calcium supplements come in 500mg or 1,000mg tablets. The common assumption is that the body absorbs the full amount. It does not. Calcium absorption is dose-dependent, and the fraction absorbed drops as the dose increases. This is not a defect in the supplement. It is how the transporter works.

Heaney et al. (1990, J Bone Miner Res) measured true fractional calcium absorption using isotope tracers in healthy adult women under meal conditions across loads ranging from 15mg to 500mg. At the lowest loads, approximately 64% of the calcium was absorbed. At 500mg, it dropped to about 29%. The relationship was highly inversely correlated with the log of the dose (P < 0.001). Harvey et al. (1988, J Bone Miner Res) extended this to higher doses using both calcium carbonate and calcium citrate at 200, 500, 1,000, and 2,000mg in 21 healthy subjects. Urinary calcium increased rapidly at the 200 and 500mg doses but showed only a slight additional increase at 1,000 and 2,000mg. The transporter was effectively saturated.

The physiology explains why. Calcium crosses the intestinal wall through two distinct pathways. Active transport is the primary route at lower intakes. It is transcellular, energy-dependent, and requires vitamin D to upregulate the transport proteins (TRPV6, calbindin) in the duodenum. This pathway is efficient but saturable. Once it reaches capacity, additional calcium can only be absorbed by passive paracellular diffusion, which occurs along the length of the intestine but at a much lower rate, roughly 5-10% of additional calcium above the saturation point. So a 1,000mg dose does absorb more total calcium than a 500mg dose, but the additional 500mg contributes relatively little because it is relying almost entirely on passive diffusion.

This is where the split-dose recommendation comes from, and where honesty matters. Splitting 1,000mg into two 500mg doses taken hours apart means each dose encounters an unsaturated active transport system. The math: 500mg at ~29% twice = approximately 290mg absorbed. 1,000mg at ~28% once = approximately 280mg absorbed. The difference is about 10mg. That is real but modest. It is not the dramatic doubling you see with vitamin C split dosing. The practical benefit of splitting calcium is less about the absorption math and more about reducing gastrointestinal side effects (bloating, constipation, gas), which are more common with calcium carbonate at high single doses. Splitting the dose is still the right recommendation, but for comfort and tolerability as much as for absorption.

The form of calcium changes the picture in ways most people do not consider. Calcium carbonate is 40% elemental calcium by weight and is the most common form. It requires stomach acid for dissolution, which means it should be taken with food. People who take calcium carbonate on an empty stomach, or who are on proton pump inhibitors or H2 blockers, will absorb substantially less. Recker (1985) showed that individuals with achlorhydria absorbed almost no calcium from calcium carbonate taken without food. Calcium citrate is 21% elemental calcium, meaning you need more tablets to get the same dose, but it does not require stomach acid and can be taken on an empty stomach. Harvey 1988 showed calcium citrate had significantly higher fractional absorption than calcium carbonate at every dose tested. The absorption from 500mg of calcium as citrate exceeded the absorption from 2,000mg of calcium as carbonate. That is a formulation difference, not a dose difference.

Two factors shift the entire curve. Vitamin D status directly affects active calcium transport. Without adequate vitamin D, the transcellular pathway underperforms regardless of dose. This is why calcium and vitamin D are co-recommended. Age also matters. Fractional calcium absorption declines by approximately 0.2% per year after age 40 (Heaney 1989), and declines more sharply after menopause due to estrogen withdrawal reducing intestinal calcium transport efficiency. An older adult absorbs less from the same dose than a younger one.

One interaction worth flagging: calcium competes with iron for DMT1 transport in the intestine. Taking calcium and iron at the same meal can reduce iron absorption by 50-60% in single-meal studies (Hallberg, 1991). If you take both, separate them by at least two hours. The same competition applies to zinc and magnesium to a lesser degree. This is not a reason to avoid calcium. It is a reason to think about timing.

The bigger picture: dietary calcium from food, consumed in small amounts across the day, is absorbed far more efficiently than a single large supplement dose. A cup of yogurt (300mg) absorbed at ~36% delivers about 108mg. Three servings across the day delivers ~324mg absorbed. A 1,000mg supplement delivers about 280mg absorbed. The food wins on efficiency even before you account for the protein and lactose in dairy, both of which enhance calcium absorption. For most people eating a varied diet, the gap between dietary calcium and the RDA (1,000-1,200mg) can be closed with a modest 500mg supplement taken with a meal, not with a 1,000mg megadose taken once.

Heaney et al., J Bone Miner Res, 1990

Harvey et al., J Bone Miner Res, 1988

19/04/2026

𝗖5‑𝗧1 𝗿𝗮𝗱𝗶𝗰𝘂𝗹𝗮𝗿 𝗽𝗮𝗶𝗻 𝘄𝗶𝘁𝗵𝗼𝘂𝘁 𝗮𝗿𝗺 𝗽𝗮𝗶𝗻

Lower cervical levels (C4–C5, C5–C6, C6–C7, C7–T1) are the most common sites for disc herniations and spondylosis. Given that all the roots exiting at these levels form the brachial plexus, it is common to have radiating pain down the arm or numbness and weakness in the upper extremities.

Patients with one of these painful radiculopathies might have neck pain, arm pain or both. When both are present, the identification of the pathologic level should be easier since they tend to follow dermatomal and myotomal distribution of symptoms.

🤷 In cases of isolated neck pain, the diagnosis becomes much more challenging because of the lack of a typical pain distribution.

📘 A new scoping review by Carmichael and colleagues of (https://www.sciencedirect.com/science/article/pii/S2666548425000393) 86 studies (1957–2022) demonstrates that scapular pain is a common feature of cervical radiculopathy (72% of studies), ranking third behind neck (88%) and arm (85%) pain. Findings challenge the clinical assumption that arm symptoms are necessary for diagnosis, as evidence suggests scapular pain may precede arm pain by weeks. The C7 nerve root shows the strongest association with scapular pain. These insights could enable earlier diagnosis of cervical radiculopathy when isolated scapular pain is present.

Neck pain is a vast entity and patients tend to label it “neck pain” even when the pain is located in-between the scapulae or near the shoulder and axilla.

📘 According to a recent publication by Redaelli and colleagues, there are typical pain locations which correlate with a specific root in the majority of cases (https://pubmed.ncbi.nlm.nih.gov/38191741/, s. also Tanaka et al. https://pubmed.ncbi.nlm.nih.gov/16924193/)

👉 C5 nerve root impingement causes pain on top of the shoulder radiating to the deltoid.

👉 C6 causes pain radiating to the supraspinous fossa.

👉 C7 causes pain medial to the spine of the scapula and can also cause pain in the axilla and the pectoral region, just below the clavicle.

👉 C8 causes pain along the medial border of the scapula, below the spine of the scapula and the pain can also radiate into the anterior chest but lower in the axilla than with C7 radiculopathy.

👉 Finally, T1 typically causes pain medial to the tip of the scapula, lower in the axilla than with C7 or 8 and into the lower anterior chest and is frequently described as a stabbing sensation . These pains, when present on the left side, can be mistaken for angina and have been called “cervical angina” 🖤 (https://pubmed.ncbi.nlm.nih.gov/33108845/).

❌So, if your patient has pain in their shoulder blade, remember: "𝗔𝘀𝘀𝗲𝘀𝘀, 𝗱𝗼𝗻’𝘁 𝘁𝗿𝗶𝗴𝗴𝗲𝗿" (;-).

📸 Adapted from: Typical patterns of pain in (a) C5; (b) C6, (c) C7; (d) C8 and (e) T1 radiculopathies. https://pubmed.ncbi.nlm.nih.gov/38191741/

13/04/2026

Exercising while sleeping less than 7 hours per night might do more harm than good: a study linked that pattern to biological signs of premature aging!

And vice versa: slowed biological aging with more sleep.

😮 I’d never work out again if I stuck to days when I had more than 7 hours sleep!

But here we go with CORRELATIONS again, sigh. Every time you hear “link” or “association,” always ask: rather than causing each other, maybe both caused by something else?

For instance: maybe many people sleep AND age poorly for shared reasons! (Also, self-reported sleep is super sloppy data.)

SOURCE: PMID 38486063

~ Paul Ingraham, PainScience.com publisher

12/04/2026

Vitamin B12 is absorbed through two pathways. The first is intrinsic factor, a protein produced by parietal cells in the stomach. IF binds B12 in the small intestine and carries it across the gut wall via a receptor called cubilin in the distal ileum. This pathway is efficient but has a hard ceiling: it saturates at roughly 1.5 µg per dose. No matter how much B12 you swallow beyond that, IF cannot carry any more.

The second pathway is passive diffusion. About 1 to 2% of any oral dose diffuses across the intestinal lining without IF, and this occurs along the entire length of the gut. At dietary doses, this pathway is negligible. At supplement doses, it becomes the primary route of absorption.
Adams et al. (1971, Scand J Gastroenterol) measured whole body retention of radiolabeled cyanocobalamin at different doses. At 1 µg, roughly 50% was retained. At 5 µg, about 20%. At 25 µg, just over 5%. The NIH Office of Dietary Supplements reports approximately 2% absorption at 500 µg and 1.3% at 1,000 µg.

The fraction drops dramatically. But the total amount absorbed keeps rising. At 1 µg you absorb about 0.5 µg. At 1,000 µg you absorb roughly 13 µg total, of which approximately 10 µg comes from passive diffusion alone. The RDA is 2.4 µg. Even the backup pathway, working at 1% efficiency, delivers more than four times your daily requirement from a single pill.

This is the basis for high-dose oral B12 as an alternative to injections in patients who lack intrinsic factor. The NIH notes that high-dose oral supplementation "may be another treatment option" for pernicious anemia, though injections remain standard first-line therapy and the available randomized controlled trials comparing the two approaches are considered limited in quality.
One important nuance: absorbing B12 into your bloodstream is only the first step. After absorption, B12 must bind to a transport protein called transcobalamin to reach your cells. This complex, holotranscobalamin, is the biologically active fraction. It represents only about 20 to 30% of the total B12 circulating in your blood. The remaining 70 to 80% rides on a separate protein called haptocorrin, which does not deliver B12 to most tissues.

This is why serum B12 can be misleading as a status marker. A person can have a "normal" total serum B12 level while their holotranscobalamin, the fraction that actually delivers B12 to cells, is low. Methylmalonic acid is a more sensitive functional marker because it rises when cellular B12 is genuinely insufficient, regardless of what total serum B12 shows.

Absorption determines how much B12 enters your blood. Transport determines how much reaches your cells. Testing only total serum B12 measures neither of these processes accurately.

Adams et al., Scand J Gastroenterol, 1971
NIH Office of Dietary Supplements, 2024
Allen et al., J Nutr, 2018

12/04/2026

Most people think Vitamin D is “just a vitamin," and, indeed, it is a vitamin… but this chart shows it behaves more like a hormone (a feature of several vitamins) that controls hundreds of processes in your body.

Sunlight hits your skin → your liver rewires the molecule → your kidneys activate it → and then this tiny hormone starts regulating everything from immunity to calcium to gene expression.

This diagram shows what textbooks never make simple:

Vitamin D is controlling your:

☀️ Immune response
☀️ Bone building
☀️ Muscle function
☀️ Hormone signaling
☀️ Cell growth & cell death
☀️ Inflammation
☀️ Cancer-protective pathways
☀️ Calcium & phosphorus absorption
☀️ Even gene transcription inside the nucleus

Every cell with a Vitamin D receptor (VDR) is listening.
That includes your brain, thyroid, pancreas, immune cells, prostate, breast tissue, colon, bones, and more.

Look at what’s happening in the diagram:

🔸 UVB light converts 7-dehydrocholesterol in the skin into previtamin D₃
(this step only activates with the right wavelength of sunlight)

🔸 The liver turns it into 25(OH)D3 (the lab marker everyone measures)
This is the “circulating form” (the one your doctor tests).

🔸 The kidney turns THAT into the active hormone, 1,25(OH₂)D3
This is the molecule that actually controls your genes.

🔸 Immune cells can ALSO activate Vitamin D on their own
Meaning your vitamin D status directly affects how strongly or weakly your immune system reacts.

🔸 Bones, thyroid, parathyroid, and gut are all communicating using this one signaling molecule
A full endocrine network most people never knew existed.

Vitamin D isn't just about “strong bones.”
It’s a biochemical communication system that your entire physiology depends on.

And deficiency doesn’t just cause low energy, it disrupts every node in this network.

Sunlight, diet, supplements, metabolism, inflammation, liver health, kidney function…
They all determine whether this system works or collapses.

source:
Holick, M. F. (2014). Cancer, sunlight and vitamin D. Journal of Clinical & Translational Endocrinology, 1(4), 179–186

06/04/2026

𝐓𝐡𝐞 𝐇𝐢𝐝𝐝𝐞𝐧 𝐂𝐮𝐥𝐩𝐫𝐢𝐭 𝐁𝐞𝐡𝐢𝐧𝐝 𝐋𝐨𝐰𝐞𝐫 𝐁𝐚𝐜𝐤 𝐏𝐚𝐢𝐧: 𝐔𝐧𝐝𝐞𝐫𝐬𝐭𝐚𝐧𝐝𝐢𝐧𝐠 𝐭𝐡𝐞 𝐂𝐚𝐫𝐭𝐢𝐥𝐚𝐠𝐢𝐧𝐨𝐮𝐬 𝐄𝐧𝐝𝐩𝐥𝐚𝐭𝐞 𝐚𝐧𝐝 𝐈𝐧𝐭𝐞𝐫𝐯𝐞𝐫𝐭𝐞𝐛𝐫𝐚𝐥 𝐃𝐢𝐬𝐜 𝐃𝐞𝐠𝐞𝐧𝐞𝐫𝐚𝐭𝐢𝐨𝐧

⬛ Low back pain (LBP) is one of the leading causes of disability worldwide, and a primary driver of this pain is Intervertebral Disc Degeneration (IDD). While many of us imagine IDD as simply a "slipped" or "worn out" disc, a recent comprehensive review article sheds light on a less-discussed but critically important structure in the spine: the cartilaginous endplate (CEP).

𝐓𝐡𝐞 𝐒𝐩𝐢𝐧𝐞’𝐬 𝐍𝐮𝐭𝐫𝐢𝐭𝐢𝐨𝐧𝐚𝐥 𝐁𝐫𝐢𝐝𝐠𝐞: 𝐖𝐡𝐚𝐭 𝐢𝐬 𝐭𝐡𝐞 𝐂𝐄𝐏?

⬛ The intervertebral disc (IVD) holds a unique distinction: it is the largest avascular (blood vessel-free) structure in the human body. Because it lacks a direct blood supply, it relies almost entirely on surrounding structures for nutrients and waste removal.
⬛ The CEP is a thin layer of translucent cartilage located at the top and bottom edges of the vertebral bodies. It serves two vital roles:

🧩 Mechanical Support: It anchors the disc and evenly distributes compressive loads.
🩸 The Nutrient Highway: The CEP houses a dense microvascular network that acts as a "bridge" for nutrient diffusion. Research indicates that axial nutrient diffusion (through the CEP) is three times higher than radial diffusion (through the outer disc).
⬛ When the CEP degrades—becoming stiffer, less permeable, and calcified—it essentially starves the disc of nutrients, initiating the cascade of IDD.

𝐅𝐢𝐯𝐞 𝐊𝐞𝐲 𝐓𝐫𝐢𝐠𝐠𝐞𝐫𝐬 𝐨𝐟 𝐂𝐄𝐏 𝐃𝐞𝐠𝐫𝐚𝐝𝐚𝐭𝐢𝐨𝐧

⬛ The breakdown of the CEP is a slow, complex process driven by several distinct factors.
⏳ Natural Degeneration: The human CEP actually begins degenerating around age 2. As we age, cell apoptosis accelerates, calcified foci form, and the microvascular network shrinks, severely reducing nutrient diffusion.
🧬 Genetics: IDD has a surprisingly strong familial link. Twin studies show that up to 74% of lumbar disc degeneration variation can be attributed to genetic factors. Mutations in genes coding for essential structural collagens, such as COL2A1 and COL9A2, directly accelerate matrix degradation and CEP calcification.
🛡️ Immune Responses: A healthy IVD is considered an "immune-privileged" tissue, completely isolated from the body's immune system by the CEP barrier. When the CEP is damaged, this barrier breaks. Immune cells flood the disc, recognizing the inner tissue as foreign, and launch an aggressive inflammatory response that further destroys the tissue.
🏋️ Mechanical Injury: Chronic high-load axial pressure can crack the weak center of the CEP. This allows the inner disc material to protrude into the bone, forming what are known as Schmorl's nodes.
🚬 Smoking: Ni****ne constricts the microvascular network within the CEP and significantly reduces the concentration of glycosaminoglycan (GAG), a crucial protein for maintaining disc elasticity. Even passive smoking has been shown to alter the circadian rhythms of disc cells.

𝐓𝐡𝐞 𝐕𝐢𝐜𝐢𝐨𝐮𝐬 𝐂𝐲𝐜𝐥𝐞: 𝐌𝐨𝐝𝐢𝐜 𝐂𝐡𝐚𝐧𝐠𝐞𝐬

⬛ The article highlights a critical imaging finding known as Modic changes—which are MRI signal changes in the vertebral bone marrow adjacent to a damaged disc.
⬛ A damaged CEP acts as a leaky filter, allowing inflammatory proteins and matrix-degrading enzymes to escape the disc and irritate the surrounding bone. In turn, the bone marrow's immune response further attacks the CEP.
⬛ This creates a vicious, positive feedback loop of inflammation and degeneration that is notoriously difficult to stop.

𝐄𝐦𝐞𝐫𝐠𝐢𝐧𝐠 𝐓𝐫𝐞𝐚𝐭𝐦𝐞𝐧𝐭𝐬: 𝐅𝐫𝐨𝐦 𝐌𝐨𝐥𝐞𝐜𝐮𝐥𝐞𝐬 𝐭𝐨 𝐒𝐜𝐚𝐟𝐟𝐨𝐥𝐝𝐬

⬛ Current surgical and non-surgical treatments primarily manage symptoms without restoring the disc's biological function. However, modern regenerative medicine is targeting the CEP directly.
🧬 Molecular Therapy: In the early stages of IDD, scientists are experimenting with injecting enzymes (like MMP8) or calcium-binding compounds directly into the CEP to decalcify it and clear out molecular debris, thereby reopening the nutrient pathways.
🧫 Cell Transplantation: Researchers have discovered that the CEP contains its own resident stem cells. Using exosomes derived from these healthy CEP stem cells can suppress cell death pathways in degenerating discs.
🧱 Tissue Engineering: For late-stage IDD, scientists are developing 3D-bioprinted scaffolds and composite biomaterials (like "eDAPS") designed to replace the damaged CEP. These scaffolds encourage native cells to migrate into the implant and generate fresh tissue and blood vessels.

𝐓𝐡𝐞 𝐇𝐨𝐫𝐢𝐳𝐨𝐧 𝐨𝐟 𝐓𝐫𝐚𝐝𝐢𝐭𝐢𝐨𝐧𝐚𝐥 𝐂𝐡𝐢𝐧𝐞𝐬𝐞 𝐌𝐞𝐝𝐢𝐜𝐢𝐧𝐞 (𝐓𝐂𝐌)

⬛ Interestingly, the review details extensive research into natural compounds derived from TCM that protect the CEP at a cellular level.
🌿 Curcumin (from Turmeric): Suppresses cell apoptosis via autophagy pathways and protects the CEP from mechanical stress.
🌱 Icariin (from Epimedium): Protects against CEP calcification by activating mitochondrial autophagy and blocking inflammatory cell death (ferroptosis).
🧪 TCM Compound Formulas: Formulas like Shen Sui Tong Zhi have been shown to target the NF-κB signaling pathway, downregulating inflammatory factors in the CEP.

𝐖𝐡𝐚𝐭’𝐬 𝐍𝐞𝐱𝐭?

⬛ While targeting the cartilaginous endplate represents a massive leap forward in treating the root cause of back pain, challenges remain.
⬛ Many modern bio-scaffolds struggle to mimic the mechanical strength of natural bone and cartilage.
⬛ Furthermore, much of the research—particularly regarding TCM—is currently limited to in vitro studies and requires further in vivo clinical validation.
⬛ Ultimately, the consensus is clear: saving the spine requires saving the endplate.
⬛ By bridging cutting-edge bioengineering with traditional pharmacological therapies, science is inching closer to treatments that don't just mask lower back pain, but actually reverse it.

04/04/2026

Resistance training can reduce body fat percentage while simultaneously improving grip strength, representing an effective management strategy for sarcopenic obesity, reports a systematic review and meta-analysis in BMC Geriatrics.

Link in the comments.

26/03/2026

26/03/2026

Timing of exercise may help with type 2 diabetes

Circadian clock gene rhythms are disrupted in type 2 diabetes, contributing to impaired glucose metabolism and hormonal dysregulation.

Exercise acts as a zeitgeber (time-giver) that modulates internal biological clocks, with timing emerging as an important factor for metabolic outcomes in type 2 diabetes.

Afternoon and evening exercise (moderate to high intensity) consistently improves glycem ic control and insulin sensitivity in type 2 diabetes, whereas morning exercise has little effect or may worsen metabolism by raising blood glucose levels.

Afternoon exercise in type 2 diabetes is associated with lower cortisol and inflammation levels, as well as greater oxidative capacity, compared with morning exercise.

The timing-dependent effects of exercise in type 2 diabetes appear to be intensity dependent, highlighting an important interaction between when and how intensely individuals with type 2 diabetes exercise.

https://www.cell.com/trends/endocrinology-metabolism/fulltext/S1043-2760(26)00030-5
https://sciencemission.com/metabolism-in-T2D