World Osteoporosis Day — A Hidden Risk You Might Overlook

 Tiejun Tang

Today is World Osteoporosis Day. Osteoporosis is a global health issue, and with the increasing aging of the population, its incidence continues to rise. According to the International Osteoporosis Foundation (IOF), about 200 million people worldwide suffer from osteoporosis. Every three seconds, someone experiences a fracture due to osteoporosis.

There are many causes of osteoporosis. Advancing age, decreased estrogen levels in postmenopausal women, and vitamin D deficiency are well-known risk factors. However, I would like to draw attention to another often-overlooked cause of osteoporosis, hoping to raise awareness among both doctors and patients.

Over the past two years, I have seen several patients diagnosed with osteoporosis, one of whom even suffered a pathological lumbar fracture. The common factor among these patients was long-term use of proton pump inhibitors (PPIs), a class of Western medications used to suppress stomach acid.

Studies have shown that long-term PPI use may be associated with an increased risk of hip, spine, and overall fractures. This may be due to reduced calcium absorption or a direct effect of PPIs on bone cell function [1]. Research has reported that five commonly used PPIs in clinical practice have varying degrees of adverse effects leading to osteoporosis [2].

There are several possible mechanisms by which PPIs may induce osteoporosis. First, gastric acid plays an essential role in the ionization of dietary calcium, which is critical for calcium absorption. PPIs, by inhibiting gastric acid secretion, may interfere with this process, thereby impairing calcium absorption[3]. The second possible mechanism is that PPIs directly affect bone metabolism. Studies have found that omeprazole may increase bone resorption by upregulating osteoclast gene expression and promoting the release of calcium ions into the bloodstream, thus influencing bone cells [4].

To prevent PPI-induced osteoporosis, there are two possible strategies. One is to use H2 receptor antagonists as an alternative to PPIs, which may reduce the risk of osteoporosis, though long-term use may cause other side effects. Another approach is to use natural herbal medicines as substitutes for Western acid-suppressing drugs.

Traditional Chinese Medicine (TCM) has shown great potential in both the prevention and treatment of osteoporosis, with its multi-target and multi-pathway regulatory effects. Active compounds in Chinese herbs—such as flavonoids, polyphenols, saponins, and polysaccharides—can modulate key signaling pathways including Wnt/β-catenin and RANKL/OPG. These effects promote osteoblast differentiation, inhibit osteoclast activity, alleviate oxidative stress and inflammation, and improve gut microbiota imbalance, ultimately restoring bone microenvironment homeostasis [5].

In my previous blog posts, I have discussed the mechanisms by which Chinese herbalmedicine can prevent and treat vitamin D deficiency, as well as its therapeuticeffects on osteoarthritis. On this World Osteoporosis Day 2025, I would like to remind everyone be aware of PPI-induced osteoporosis—do not harm your bones in the process of protecting your stomach.

References

1. Saowanee N. et al. Proton pump inhibitors and risk of fracture: a systematic review and meta-analysis of observational studies. Am
   J Gastroenterol. 2011 Jul;106(7):1209-18.
2. Jingkai Di et al. Evaluating the risk of osteoporosis-related adverse events with proton pump inhibitors: a pharmacovigilance study. Front Pharmacol. 2025 Jul 11;16:1582908.
3. G. Graziani et al. Effect of gastric acid secretion on intestinal phosphate and calcium absorption in normal subjects. Nephrol Dial Transplant. 1995;10(8):1376-80.
4. Mohamed I. Zanaty et al. Effect of Omeprazole on Osteoblasts and Osteoclasts in vivo and in the in vitro Model Using Fish Scales. Biochemistry (Mosc). 2021 Oct;86(10):1192-1200.
5. Chaoqun Song et al. The role of active constituents in traditional Chinese medicine for primary osteoporosis: a mechanistic review. Front Endocrinol (Lausanne). 2025 Sep 16;16:1647984.

Is Eating Chili Peppers Good or Bad for Your Heart?

 Tiejun Tang

For centuries, chili peppers have added heat and flavor to cuisines around the world. But beyond the spice, scientists have been asking a fiery question: is chili good or bad for the human heart? Recent research suggests that moderate chili consumption might actually protect cardiovascular health — though not everyone agrees.

The Evidence for a Healthy Heart

Over the past decade, several large population studies have investigated the link between spicy foods and heart disease. One of the most influential was conducted in China, following nearly half a million adults for seven years. The researchers found that those who ate spicy food almost every day had a 14% lower risk of death compared with those who rarely did ^[1]. The reduction was particularly strong for deaths due to ischemic heart disease and stroke.

Similar results appeared in Italy’s Moli-sani study, which tracked over 22,000 adults for eight years. Regular chili eaters had a significantly lower risk of cardiovascular and all-cause mortality, even after accounting for other lifestyle factors such as smoking, body weight, and Mediterranean-diet adherence^[2].

When these and other studies were pooled together, meta-analyses confirmed the trend: frequent chili consumption was consistently linked to lower overall and heart-related death rates ^[3,4].

What Could Explain the Benefit?

Scientists believe the active compound capsaicin, which gives chili its heat, may help explain these effects. Capsaicin activates a receptor called TRPV1 in blood vessels and nerve endings. This can lead to vasodilation (wider blood vessels), improved blood flow, and lower inflammation ^[5].

Laboratory experiments and small human trials have shown that capsaicin may reduce cholesterol levels, improve blood vessel flexibility, and boost metabolism ^[6]. These effects could, in theory, lower cardiovascular risk over time.

But the Story Isn’t Entirely Sweet (or Spicy)

Not all findings are conclusive. Most of the strongest human studies are observational, meaning they can show an association but not prove that chili itself causes better heart health. People who eat more chili might also have other habits — such as more plant-based diets or higher physical activity — that contribute to their good outcomes.

In addition, excessive spicy food can cause stomach irritation, worsen acid reflux, or lead to discomfort in people with gastritis or ulcers. Very high doses of capsaicin, especially in supplement form, have been linked to rare cases of coronary vasospasm, a temporary narrowing of heart arteries ^[7]. Howeve, such effects are uncommon at normal dietary levels.

How Much Is Too Much?

So far, the evidence suggests that moderate chili consumption — a few times a week, as part of a balanced diet — is safe and may offer modest cardiovascular benefits. Those who enjoy spicy foods can continue to do so, provided it doesn’t cause gastrointestinal distress. On the other hand, taking high-dose capsaicin supplements for heart protection is not recommended until large, long-term clinical trials confirm clear benefits.

The Takeaway

The spice of life may indeed be good for your heart — in moderation. While scientists continue to study the exact effects of capsaicin, the best advice remains simple: eat a balanced diet rich in fruits, vegetables, and whole foods, and if you like your meals with a little kick, that’s probably just fine for your heart.

References

1. Lv J et al. Consumption of spicy foods and total and cause-specific mortality: a population-based cohort study. BMJ. 2015;351:h3942.
2. Bonaccio M et al. Chili pepper consumption and mortality in Italian adults (Moli-sani study). J Am Coll Cardiol. 2019;74(25):3139-3149.
3. Yamani N et al. Meta-analysis evaluating the impact of chili-pepper intake on all-cause and cardiovascular mortality: A systematic review. Ann Med Surg (Lond). 2021; 8;70:102774
4. Ofori-Asenso R et al. Association of Spicy Chilli Food Consumption With Cardiovascular and All-Cause Mortality: A Meta-Analysis of Prospective Cohort Studies. Angiology. 2021;72(7):625-632.
5. Sreepadaarchana Munjuluri .Capsaicin and TRPV1 Channels in the Cardiovascular System: The Role of Inflammation. Cells. 2021 Dec 22;11(1):18.
6. Vijaya Juturu . Capsaicinoids Modulating Cardiometabolic Syndrome Risk Factors: Current Perspectives. J Nutr Metab. 2016 May 23;2016:4986937.
7. Ozgur Sogut . Acute myocardial infarction and coronary vasospasm associated with the ingestion of cayenne pepper pills in a 25-year-old male. Int J Emerg Med. 2012 Jan 20;5:5.

Is the Famous TCM Formula Angong Niuhuang Wan Effective or Ineffective?

 Tiejun Tang   

Recently, I came across a video on YouTube by a highly popular YouTuber celebrity, Mr. Wang, who claimed that the traditional Chinese patent medicine Angong Niuhuang Wan has no therapeutic benefit in treating acute stroke and performs no better than a placebo. Based on this, he concluded that this long-celebrated and expensive remedy is completely ineffective. Could it really be true that a classic formula used by traditional Chinese medicine (TCM) practitioners for hundreds of years is useless? This article aims to analyze and discuss this issue in detail.

 Source of the Controversy

Mr. Wang’s argument was based on a recently published study in the Chinese Medical Journal (English edition) ^[1]. The study included 117 patients from 17 hospitals across China — 57 in the Angong Niuhuang Wan treatment group and 60 in the placebo group. The conclusion stated that there was no significant difference in efficacy between the two groups. The research was conducted by the Peking Union Medical College Hospital, one of the most prestigious Western medical institutions in China, and published in a top-tier Chinese medical journal. Unsurprisingly, the findings quickly drew attention and spread widely across both mainstream and social media.

Angong Niuhuang Wan was formulated by Wu Jutong (1758-1836), a renowned physician of the Qing dynasty and an expert in the study of febrile diseases. The formula has the functions of clearing heat, resolving phlegm, detoxifying, and opening the orifices. It has been used for over 200 years to treat high fever with coma, stroke-induced unconsciousness, and convulsions in children. It is known as one of the “Three Cooling and Orifice-Opening Treasures” for treating stroke of the Close Symdrome in TCM. So, why did a formula with long-standing clinical efficacy fail to show benefit in a randomized, double-blind clinical trial?

 Clinical Research Evidence

A research team from the China Academy of Chinese Medical Sciences published a meta-analysis with a much larger sample size, reporting different conclusions ^[2]. The study included 28 randomized controlled trials (RCTs) with a total of 2,745 acute stroke patients (1,375 in the experimental group and 1,370 in the control group). The results showed that Angong Niuhuang Wan  significantly improved the overall effective rate, Glasgow Coma Scale (GCS) score, Mini-Mental State Examination (MMSE) score, Activities of Daily Living (ADL) score, and Barthel Index score. It also reduced the National Institutes of Health Stroke Scale (NIHSS) score and serum brain natriuretic peptide (BNP) levels. No serious adverse events were reported, indicating good safety.

 Experimental Research Evidence

Experimental studies have also provided insights into the mechanisms of Angong Niuhuang Wan.

One study established a cerebral ischemia–reperfusion injury (CIRI) model via middle cerebral artery occlusion and used acetylomics and proteomics to explore the neuroprotective effects of  Angong Niuhuang Pill (ANP). The results showed that ANP pretreatment significantly reduced neurological deficit scores and infarct volume, increased regional cerebral blood flow (rCBF), and decreased neuronal apoptosis. Further analysis revealed that ANP regulates autophagy at the transcriptional level via H4K16ac modification, promotes sirtuin 1 (SIRT1) accumulation, and modulates the SIRT1–H4K16ac axis to inhibit excessive autophagy, thereby exerting neuroprotective effects^[3].

Another study used network pharmacology to identify key active compounds in ANP and predict its potential pathways. Five bioactive equivalent combinatorial components (BECCs) were identified, which demonstrated comparable effects to ANP in improving motor recovery in zebrafish and reducing neurological deficits and infarct volume in MCAO mice, mainly through the PI3K/AKT signaling pathway^[4].

More recently, researchers applied ultra-high-performance liquid chromatography coupled with quadrupole-Orbitrap high-resolution mass spectrometry (UHPLC-Q-Exactive-Orbitrap-MS) to identify chemical constituents in ANP and its serum-absorbed components. Using network pharmacology and transcriptomic analysis, they found that 169 compounds were identified in total, 13 of which were detected in serum and interacted with 91 key targets. ANP significantly reduced serum TNF-α and IL-6 levels, as well as hypothalamic COX-2 and PGE2 levels. It upregulated NRF2 and KEAP1 expression while downregulating TLR4, IL-17A, p-P65/P65, TNF-α, and NLRP3. In LPS-induced RAW264.7 cells, ANP inhibited excessive secretion of inflammatory mediators (NO, IL-6, TNF-α), suppressed iNOS and CD86 expression, and enhanced NRF2 expression, thereby demonstrating strong anti-inflammatory and antioxidant effects^[5].

Discussion

Experimental studies have clearly demonstrated the multi-target mechanisms and material basis underlying the efficacy of Angong Niuhuang Wan. Why, then, do some clinical trials report conflicting results? What causes these discrepancies? And ultimately — is the medicine effective or not?

In my view, the key to evaluating the efficacy of a Chinese medicine lies in syndrome differentiation. No matter how famous or expensive a medicine is, if it is not prescribed according to the correct diagnosis (zheng), it will not be effective — and vice versa.

In TCM, stroke patients with impaired consciousness are classified under the category of Close Syndrome (闭证), which can be further divided into Heat Close syndrome  and Cold Close syndrome. For heat close syndrome, depending on whether heat or phlegm predominates, and whether convulsions are present, practitioners select different formulas. The “Three Cooling and Orifice-Opening Treasures” — Angong Niuhuang Wan, Zhibao Dan, and Zixue Dan— are used for heat closed syndrome, whereas Suhexiang Wan is used for cold close syndrome.

Western medicine researchers often administer Angong Niuhuang Wan to all stroke patients with coma, without distinguishing between heat and cold syndromes — which contradicts TCM principles. Wu Jutong would never have used a randomized double-blind method to treat patients; instead, he and generations of TCM practitioners after him applied individualized treatments according to syndrome differentiation, saving countless lives in the process. The enduring use of this formula for over 200 years is itself strong evidence of its clinical value.

Therefore, evaluating Chinese medicine efficacy using Western evidence-based criteria alone is inappropriate and misleading. TCM requires its own evaluation system — one that respects syndrome differentiation and the holistic principles of Chinese medicine. Only through research designed on these foundations can we truly assess the therapeutic effects of formulas like Angong Niuhuang Wan.

 References

1. Li S. Safety and efficacy of Angong Niuhuang Pills in patients with moderate-to-severe acute ischemic stroke (ANGONG TRIAL): A randomized double-blind placebo-controlled pilot clinical trial. Chin Med J (Engl). 2025 Mar 5;138(5):579–588.
2. Meng X. Effectiveness and safety of Angong Niuhuang Pill in treatment of acute stroke: A systematic review and meta-analysis.  J Tradit Chin Med. 2023 Aug;43(4):650–660.
3. Wang L.  Angong Niuhuang Pill pretreatment alleviates cerebral ischemia-reperfusion injury by inhibiting excessive autophagy through the SIRT1-H4K16ac axis.  J Ethnopharmacol. 2025 Jan 31;340:119214.
4. Zhang X. A newly discovered bioactive equivalence of combinatorial components of Angong Niuhuang Pill improves ischemic stroke via the PI3K/AKT axis.  J Ethnopharmacol. 2025 Mar 13;343:119453.
5. Gao F.  Explore the chemical components of Angong Niuhuang Pill and its potential mechanisms for fever treatment based on UHPLC-Q-Exactive Orbitrap HRMS, transcriptomics, and experiment verification.  J Ethnopharmacol. 2025 Sep 5;354:120542.