Not Just Expensive Urine

“You’re wasting your money. Vitamins just give you expensive urine.“
How many times have you said this to a patient?
It is time to revisit the evidence

Protecting the mind, relationships, and the will to continue

In emergency medicine, we pride ourselves on evidence-based practice. We dismiss the supplement aisle. Some of that scepticism is warranted with an industry rife with pseudoscience and commercial overreach. But the evidence has moved, and many of us have not.

This article provides a practical, evidence-based framework for nutritional supplementation specifically designed for emergency physicians. It includes clinical nuances that could affect how you interpret screening tests including drug–supplement interactions that are underrecognised, dangerous, and increasingly common

Why the Emergency Physician Is Nutritionally Vulnerable

Australia is a prosperous, food-secure country in which approximately 60–65% of average caloric intake now comes from ultra-processed food. Products that are energetically dense, micronutrient-poor, and associated with systemic inflammatory signalling through gut barrier disruption (Machado, 2019; Zhang, 2025). The result is a nutritional paradox where we are overfed with calories, and undernourished in the micronutrients on which cellular repair, immune function, and longevity depend.

For emergency physicians, the exposure is compounded. Shift work disrupts circadian rhythms that govern nutrient metabolism. Sustained cortisol elevation depletes magnesium. Beta-2 agonists and inhaled corticosteroids, among the most commonly prescribed medications through the ED, deplete it further. The dietary reality of a busy department means relying on food alone to correct these deficiencies is unrealistic.

National survey data confirm the gap. Among Australian adults aged 25 and over, 20% are vitamin D deficient and a further 43% are insufficient — nearly two-thirds operating below optimal vitamin D status (Malacova, 2019). In southern states during winter, deficiency rates reach 36%. For physicians spending working hours under artificial light, rotating through night shifts, those numbers are likely higher still. Approximately 34–37% of Australians fail to meet the Estimated Average Requirement for daily magnesium intake (ABS, 2014). The emergency physician presenting with fatigue, muscle cramps, and disrupted sleep may not have a mysterious pathology. They may have a magnesium level their GP has never tested properly.

The Evidence Has Shifted

For decades, trials of multivitamin supplementation in well-nourished Western populations failed to demonstrate mortality benefit. The dismissal was, in that context, defensible. Two landmark randomised trials published in 2025 and 2026 have materially changed the picture.

The VITAL trial: 25,871 participants, randomised, double-blind, placebo-controlled found that four years of daily vitamin D3 at 2,000 IU preserved approximately 140 base pairs of leukocyte telomere length compared to placebo (Zhu, 2025). To put that in terms that mean something clinically… 140 base pairs is equivalent to roughly three years of slower biological ageing. This is not a cell study. It is a gold-standard RCT involving 25,000 people.

The COSMOS trial: 958 participants from a large randomised double-blind placebo-controlled 2×2 factorial design was published in Nature Medicine in 2026. It found that two years of daily multivitamin-mineral supplementation significantly slowed biological ageing as measured by second-generation epigenetic clocks, with a between-group difference in yearly change of −0.113 years for PCGrimAge acceleration (Li, 2026). The same COSMOS programme previously demonstrated protection of cognitive function equivalent to preserving approximately two years of cognitive age (Vyas, 2024).

Two years of a daily multivitamin slowed epigenetic ageing clocks in a 2026 Nature Medicine RCT of 958 participants. The ‘expensive urine’ dismissal is now an outdated clinical position

The mechanism is not mysterious. Emergency physicians carry background micronutrient insufficiencies that are invisible to standard bloods. A daily multivitamin reduces the gap between dietary intake and cellular requirement in a way that measurably slows biological ageing. The RCT bar has been crossed. The ‘expensive urine’ adage belongs in the same category as other well-meaning medical advice that the evidence has quietly retired

Vitamin D3 + K2: The Synergy Most Prescriptions Miss

Vitamin D is widely prescribed in Australian general practice. What is less appreciated is that high-dose vitamin D without paired vitamin K2, specifically the MK-7 form, elevates calcium absorption without adequately directing that calcium into bone. The consequence is a risk of arterial calcification (van Ballegooijen, 2017). Vitamin K2 activates matrix Gla-protein and osteocalcin, directing calcium into bone architecture rather than vascular walls.

The practical rule: D3 and K2 together, always. D3 (cholecalciferol, not D2) at 2,000–4,000 IU daily, with the MK-7 form of K2 at 100–200 mcg. Take with your largest meal as fat-soluble vitamins require dietary fat for absorption. Target 25(OH)D level 50–80 ng/mL. Do not exceed 300 mcg K2 daily.

Magnesium: Form Is Everything

When a patient or colleague reports taking magnesium and experiencing no benefit, the most likely explanation is the form of magnesium taken. Magnesium oxide is the cheapest, most widely available form, with approximately 4% bioavailability and a primary action as an osmotic laxative. It is the form sold in the majority of Australian pharmacy products. It does not correct intracellular magnesium deficiency.

Testing should use red blood cell (RBC) magnesium rather than serum magnesium. Serum levels are maintained at the expense of tissue stores and are insensitive to early deficiency (DiNicolantonio, 2018). A normal serum magnesium is consistent with significant tissue depletion.

Form	Best For	Timing	Notes	Avoid If…
Glycinate	Sleep, anxiety, general deficiency	Evening	Default choice. High bioavailability, gentle on gut.	None The safest form
L-Threonate	Cognitive function	Morning or split	Crosses blood-brain barrier. More expensive.	None
Malate	Energy, fatigue, fibromyalgia	Morning	Krebs cycle intermediate. Supports mitochondrial energy.	Evening. May be activating
Citrate	Constipation, general deficiency	Evening	Mild laxative effect. Useful for opioid-related constipation.	Prone to loose stools
Oxide ⚠️	Laxative only	—	~4% absorption. Commonest pharmacy form.	Always, if using for deficiency correction

Omega-3 Fatty Acids: The Index Nobody Tests

Most Australians have an omega-3 index below 5% and are in the high-risk category for inflammation-related disease. An omega-3 index of 8% or above is associated with a five-year increase in life expectancy (Harris, 2021). The omega-6 to omega-3 ratio evolved at approximately 1:1. The modern Western diet runs at 15:1 to 17:1 and is a structural driver of chronic low-grade inflammation.

Choose brands with independent third-party testing for mercury and oxidation markers, refrigerate after opening, and smell the capsule before taking it. Rancid fish oil is pro-inflammatory. Target 2–3g combined EPA+DHA daily.

Creatine: Beyond the Gym

Creatine monohydrate has over a thousand studies confirming safety and efficacy for muscle strength and power. The emerging evidence for cognitive function under conditions of sleep deprivation is directly relevant to emergency physicians (Forbes et al., 2022). Five grams daily, any time, no loading phase required. It is probably the most underused evidence-based supplement in clinical practice

⚠️  The Critical Clinical Trap: Berberine and PSA

This section addresses an interaction you will encounter with increasing frequency and one that carries direct consequences for prostate cancer screening.

Berberine is a plant alkaloid with multiple meta-analyses confirming effects on fasting blood glucose, HbA1c, and lipid profiles comparable to metformin (Yin, 2008; Dong, 2012). It activates AMPK, the same master metabolic switch triggered by fasting and caloric restriction. Its uptake in the longevity and metabolic health community is substantial and still growing.

What is less widely known is that berberine is a 5-alpha reductase inhibitor. Like finasteride and dutasteride, it blocks the conversion of testosterone to dihydrotestosterone and suppresses PSA production by approximately 50% at doses of 500–1,000 mg daily (Etzioni et al., 2005).

A man on berberine 500–1,000mg/day with a reported PSA of 2.5 ng/mL may have a true PSA of 5.0 — the difference between routine monitoring and urgent urological referral

The clinical consequence is direct. A man presenting for routine PSA screening while taking berberine will have his PSA halved by the supplement. A ‘normal’ PSA of 2.5 ng/mL may conceal a true value of 5.0, a value that would ordinarily prompt biopsy and investigation. A physician unaware of this interaction may falsely reassure a patient with early prostate cancer.

The correction is simple. In any man of screening age who reports berberine supplementation, multiply the observed PSA by two before clinical interpretation. The same principle applies to finasteride and dutasteride. However berberine is purchased over the counter, is not routinely recorded in medication histories, and is not spontaneously disclosed by patients who do not consider supplements to be medications.

It belongs on every emergency department’s medication reconciliation prompt. Today, not when the guidelines catch up. Additional berberine notes: cycle 8–11 weeks on, 1–2 weeks off to prevent gut microbiome adaptation; take with meals to reduce GI side effects; absolutely contraindicated in pregnancy.

What Your Prescriptions Are Costing Patients — and You

Every medication has a nutritional cost. Physicians prescribe these drugs daily and rarely discuss the downstream consequences

Medication	Nutrients Depleted	Clinical Consequence	Action
Proton pump inhibitors	Magnesium, calcium, iron, B12	Arrhythmia risk; anaemia; neuropathy	Test RBC magnesium + B12 annually
Metformin	Vitamin B12	Peripheral neuropathy mimicking diabetic neuropathy	Test B12 annually; supplement methylcobalamin if low
Statins	CoQ10 (ubiquinone)	Myalgia; reduced mitochondrial function	Ubiquinol 100–200 mg daily
Inhaled corticosteroids	Magnesium, calcium, vitamin D	Impaired bronchodilator response (low Mg)	Test RBC magnesium and vitamin D
Beta-2 agonists	Magnesium (intracellular shift + renal loss)	Reduced bronchodilator response	Test RBC magnesium; supplement if low
Combined oral contraceptive	B6, B12, folate, zinc, magnesium	Mood changes; neuropathy; anaemia	Methylated B-vitamin supplement

A Practical Protocol for the Emergency Physician

SUPPLEMENTATION PROTOCOL

The golden rule: if you cannot tell whether something is working — if there is no measurable outcome, no blood test, no subjective improvement — stop taking it. The most expensive intervention is the one that does nothing.

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References

• Australian Bureau of Statistics. Australian Health Survey: Biomedical Results for Nutrients, 2011–12. ABS; 2013.
• Australian Bureau of Statistics. Australian Health Survey: Usual Nutrient Intakes, 2011–12. ABS; 2014.
• DiNicolantonio JJ, O’Keefe JH, Wilson W. Subclinical magnesium deficiency: a principal driver of cardiovascular disease and a public health crisis. Open Heart. 2018 Jan 13;5(1):e000668. doi: 10.1136/openhrt-2017-000668
• Dong H, Wang N, Zhao L, Lu F. Berberine in the treatment of type 2 diabetes mellitus: a systemic review and meta-analysis. Evid Based Complement Alternat Med. 2012;2012:591654.
• Etzioni R, Gulati R, Falcon S, Penson DF. Impact of finasteride on the predictive performance of the Prostate Cancer Prevention Trial risk calculator. J Urol. 2005;174(4 Pt 1):1305-1309.
• Forbes SC et al. Effects of Creatine Supplementation on Brain Function and Health. Nutrients. 2022 Feb 22;14(5):921.
• Harris WS, Del Gobbo L, Tintle NL. The Omega-3 Index and relative risk for coronary heart disease mortality: Estimation from 10 cohort studies. Atherosclerosis. 2017 Jul;262:51-54.
• Li S, Hamaya R, Zhu H, Chen BH, Pereira AC, Ivey KL, Rist PM, Manson JE, Dong Y, Sesso HD. Effects of daily multivitamin-multimineral and cocoa extract supplementation on epigenetic aging clocks in the COSMOS randomized clinical trial. Nat Med. 2026 Mar;32(3):1012-1022
• Machado PP, Steele EM, Levy RB, Sui Z, Rangan A, Woods J, Gill T, Scrinis G, Monteiro CA. Ultra-processed foods and recommended intake levels of nutrients linked to non-communicable diseases in Australia: evidence from a nationally representative cross-sectional study. BMJ Open. 2019 Aug 28;9(8):e029544
• Malacova E, Cheang PR, Dunlop E, Sherriff JL, Lucas RM, Daly RM, Nowson CA, Black LJ. Prevalence and predictors of vitamin D deficiency in a nationally representative sample of adults participating in the 2011-2013 Australian Health Survey. Br J Nutr. 2019 Apr;121(8):894-904.
• Smith PK. 30 Minutes to Longevity. Brisbane; 2026. ISBN 978-1-7645982-0-0.
• van Ballegooijen AJ, Pilz S, Tomaschitz A, Grübler MR, Verheyen N. The Synergistic Interplay between Vitamins D and K for Bone and Cardiovascular Health: A Narrative Review. Int J Endocrinol. 2017;2017:7454376
• Vyas CM et al. Effect of multivitamin-mineral supplementation versus placebo on cognitive function: results from the clinic subcohort of the COcoa Supplement and Multivitamin Outcomes Study (COSMOS) randomized clinical trial and meta-analysis of 3 cognitive studies within COSMOS. Am J Clin Nutr. 2024 Mar;119(3):692-701
• Yin J, Xing H, Ye J. Efficacy of berberine in patients with type 2 diabetes mellitus. Metabolism. 2008 May;57(5):712-7.
• Zhang Q et al. Dietary advanced glycation end-products promote food allergy by disrupting intestinal barrier and enhancing Th2 immunity. Nat Commun. 2025 May 28;16(1):4960
• Zhu H et al. Vitamin D₃ and marine ω-3 fatty acids supplementation and leukocyte telomere length: 4-year findings from the VITamin D and OmegA-3 TriaL (VITAL) randomized controlled trial. Am J Clin Nutr. 2025 Jul;122(1):39-47.