Supplements

5-Hydroxytryptophan (5-HTP) is an amino acid the body produces as an intermediate step in converting dietary tryptophan into serotonin. It is sold as a supplement, commonly derived from the seeds of Griffonia simplicifolia, on the premise that boosting this precursor raises brain serotonin production. 5-HTP became popular after L-tryptophan supplements were pulled from the US market in 1989 following an outbreak of eosinophilia-myalgia syndrome (EMS) traced to a contaminated manufacturing batch; 5-HTP has not been linked to a comparable outbreak, but that episode has kept researchers and regulators cautious about this class of serotonin-precursor supplements. People take 5-HTP hoping to improve mood, anxiety, and sleep onset. Clinical evidence is limited: a small pool of older, mostly low-quality randomised trials suggests possible benefit for depression, and a newer small trial suggests modest sleep-quality benefits, but neither is well established. The most important safety issue is not efficacy but interaction risk: because 5-HTP directly increases serotonin precursor availability, combining it with serotonergic medications (SSRIs, SNRIs, MAOIs, triptans, tramadol, St John's Wort) can precipitate serotonin syndrome, a potentially severe reaction, which is why this supplement is best used short-term and under medical supervision rather than continuously and unsupervised.

Ashwagandha (Withania somnifera) is a shrub used for centuries in Ayurvedic medicine, whose root is traditionally used as an adaptogen, a substance believed to help the body handle physical and psychological stress. Modern supplements are typically standardised root extracts (commonly branded as KSM-66 or Sensoril) that concentrate withanolides, the plant's most-studied active compounds. Most human clinical research has concentrated over the last 10-15 years on stress and cortisol reduction, sleep, and exercise recovery, and this is now backed by several small-to-moderate randomised trials and a handful of meta-analyses, though individual trials generally remain small and short (weeks to a few months). Ashwagandha is usually well tolerated, but case reports have linked it to liver injury and to thyroid hormone changes in some users, and its safety in pregnancy has not been established.

Collagen is the most abundant structural protein in the body, forming a major component of skin, tendons, ligaments, cartilage, and bone. Hydrolysed collagen (collagen peptides) is collagen that has been enzymatically broken down into small, more readily absorbed peptides, usually sourced from bovine, porcine, or marine (fish) tissue. The body's own collagen production slows with age, which has driven interest in collagen supplements for skin appearance, joint comfort, and nail health. Evidence is strongest and most consistent for reducing activity-related joint pain in physically active people. Evidence for skin hydration and elasticity is positive when pooling all available trials, but that overall effect appears heavily influenced by industry funding and study quality rather than being a robust, independent finding. Evidence for nail growth is weaker still, resting mainly on small, uncontrolled studies. Collagen peptides are generally regarded as safe and well tolerated.

Lutein and zeaxanthin are dietary carotenoids, yellow-orange pigments related to beta-carotene, that the body cannot synthesise and must obtain from food (leafy greens, corn, egg yolks) or supplements. They selectively accumulate in the macula of the retina, where together with a related pigment (meso-zeaxanthin) they form the macular pigment, a natural blue-light filter and antioxidant thought to protect photoreceptors from oxidative damage. Because they are almost always studied and supplemented together in a fixed ratio, this monograph treats lutein and zeaxanthin as a single combined supplement rather than two separate ingredients. The strongest evidence for a genuine clinical benefit comes from the large AREDS2 trial, which found that a lutein+zeaxanthin combination helps slow progression to advanced age-related macular degeneration (AMD) in patients who already had intermediate or worse AMD in at least one eye, and did so more safely than the beta-carotene it can replace. In healthy people without AMD, supplementation reliably raises macular pigment optical density (a biomarker of macular carotenoid status), but whether this translates into a meaningful protective or functional benefit for people with healthy eyes is not established. Marketing claims about relieving digital eye strain or screen-related visual fatigue are not well supported: the one relevant randomised trial found no improvement in self-reported eye strain, only in objective dry-eye surface measures.

Magnesium is an essential mineral involved in several hundred enzymatic reactions in the body, including energy production, muscle and nerve function, blood glucose regulation, and blood pressure control. Many adults in high-income countries consume less magnesium than recommended, and mild deficiency is more common in people with poor diets, gastrointestinal disease, or those taking certain medications such as proton pump inhibitors or diuretics. People take magnesium supplements to correct low intake, ease muscle cramps, support sleep, or as an adjunct for migraine prevention or blood pressure control. Different salts (glycinate, citrate, oxide) vary widely in how much elemental magnesium they provide and how well that magnesium is absorbed. Most healthy adults tolerate supplemental magnesium well; the main limiting side effect at higher doses is diarrhoea, which is both dose- and form-dependent.

A multi-strain probiotic combines two or more live bacterial or yeast strains, commonly from the Lactobacillus, Bifidobacterium, Saccharomyces, or Bacillus genera, intended to support gut microbial balance. Probiotic effects are strongly strain-specific: clinical benefits demonstrated for one strain (or a specific multi-strain combination) at a specific dose do not necessarily apply to a different strain, a different combination, or even the same species from a different manufacturer, because different strains have different mechanisms, colonisation behaviour, and metabolic outputs. This means product labels matter far more for probiotics than for most other supplements: a generic "multi-strain probiotic" claim says little on its own about what a given product can be expected to do, and the claims below apply only to the specific strains studied in the cited trials. The strongest, most consistent evidence supports specific probiotic strains for preventing antibiotic-associated diarrhoea. Evidence for irritable bowel syndrome (IBS) symptom relief is real but strain-dependent, with some well-studied strains showing benefit and others showing none. Evidence for general immune support (e.g. reducing common colds) is weaker and of lower certainty. Probiotics are generally safe for healthy people, but rare, serious infections (bacteremia or fungemia) have been reported in immunocompromised, critically ill, or catheterised patients.

N-acetylcysteine (NAC) is a modified form of the amino acid cysteine, best known as the standard antidote for acetaminophen (paracetamol) overdose and as a prescription mucolytic that thins mucus in chronic respiratory disease. It is also sold as a dietary supplement because it is a precursor for glutathione, the body's major intracellular antioxidant, and has anti-inflammatory properties. People take NAC supplements hoping to support respiratory health, general antioxidant status, or as an add-on alongside standard treatment for certain psychiatric conditions such as obsessive-compulsive disorder. Human evidence is strongest for long-term use in reducing chronic bronchitis and COPD exacerbations; evidence for general antioxidant benefits and psychiatric use is more preliminary and mixed. NAC has low oral bioavailability (roughly 6-10%) and is generally well tolerated, though it can meaningfully interact with nitrate medications such as nitroglycerin.

Nicotinamide mononucleotide (NMN) is a small molecule the body uses to make nicotinamide adenine dinucleotide (NAD+), a coenzyme required for hundreds of metabolic reactions, DNA repair, and the activity of sirtuin proteins linked to cellular ageing. NAD+ levels naturally decline with age, which has driven substantial interest in NMN as an anti-ageing supplement. Animal studies, mainly in mice, have found that long-term NMN treatment can extend lifespan and improve markers of healthy ageing. Human research, however, is still at an early stage: small trials lasting weeks to a few months confirm that oral NMN reliably raises blood NAD+ levels and appears to be well tolerated in the short term, but they have not established the longevity benefits seen in animals, and human evidence for metabolic or physical performance benefits is inconsistent. People take NMN hoping to slow ageing or improve energy and metabolic health, but the direct evidence for these effects in humans remains preliminary, and no human trial has run long enough to test effects on lifespan itself.

Omega-3 fatty acids -- primarily EPA (eicosapentaenoic acid) and DHA (docosahexaenoic acid) -- are polyunsaturated fats found mainly in fatty fish and algae, used by the body to build cell membranes and to produce anti-inflammatory signalling molecules. Most people eating a typical Western diet get little EPA/DHA, which is why fish oil and algae-oil supplements are among the most widely used supplements. People take omega-3 supplements mainly to lower triglycerides, support joint comfort, and sometimes as an adjunct for mood; evidence for direct prevention of heart attacks or strokes in the general population is weaker and mixed. Supplements are sold in the natural triglyceride form found in fish oil, or as concentrated ethyl-ester preparations; the two forms differ modestly in how well they are absorbed. At the high doses used in some cardiovascular trials, omega-3 supplementation has also been linked to an increased risk of atrial fibrillation, so more is not automatically better or safer.

Taurine is a sulfur-containing amino acid (technically an amino sulfonic acid) found in high concentrations in meat, fish, and shellfish, and it is also synthesised naturally in the body from cysteine. Unlike most amino acids it is not incorporated into proteins; instead it plays roles in bile acid conjugation, regulation of cell volume, calcium handling in heart and muscle cells, and antioxidant defence. Taurine is a common ingredient in energy drinks and sports supplements, where people take it hoping to improve exercise performance and recovery, and it has also been studied as a supplement for blood pressure control and as an adjunct alongside standard treatment for heart failure. Evidence for exercise performance and blood pressure is modest but reasonably consistent across trials; evidence for heart failure is more preliminary. Taurine is generally very well tolerated, and no consistent pattern of adverse effects has been established at commonly used supplemental doses.

A B-complex supplement combines several B vitamins, typically B1 (thiamine), B2 (riboflavin), B3 (niacin), B5 (pantothenic acid), B6 (pyridoxine), B7 (biotin), B9 (folate/folic acid), and B12 (cobalamin), that the body uses as coenzymes in energy metabolism, red blood cell formation, and nervous system function. Because these vitamins participate in overlapping metabolic pathways, and deficiency of one can mask or worsen a deficiency of another (folic acid, for instance, can mask the anaemia of B12 deficiency), they are commonly combined into a single product. B-complex supplements are widely marketed for "energy" and general wellbeing, but the strongest and most consistent evidence supports a benefit specifically in people with an actual deficiency or elevated homocysteine: correcting an identified shortfall reliably resolves the associated fatigue, anaemia, or neurological symptoms, and folate plus B12 reliably lowers blood homocysteine. In people who are not deficient, evidence for improved energy, cognition, or mood is much weaker, and mostly limited to a small effect on subjective stress. High chronic doses of B6 in particular carry a documented, if uncommon, risk of peripheral neuropathy.

Vitamin D3 (cholecalciferol) is a fat-soluble vitamin the body produces in skin exposed to UVB sunlight and also obtains from diet and supplements. It is converted in the liver and kidneys into its active hormone form, which regulates calcium and phosphate absorption and is essential for bone mineralisation, and also has roles in immune and muscle function. Many people living at higher latitudes, with limited sun exposure, darker skin, or who are older have low vitamin D status, which is why supplementation is common. People take vitamin D3 mainly to correct deficiency and support bone health; evidence for other benefits, such as reduced infections, is weaker and depends heavily on baseline vitamin D status and dosing pattern. Because it is fat-soluble, it can accumulate in the body if taken in excess over long periods, unlike water-soluble vitamins that are readily excreted.

Vitamin K2 (menaquinone) is a fat-soluble vitamin that activates proteins involved in calcium handling, most notably osteocalcin, which helps direct calcium into bone, and matrix Gla protein, which helps keep calcium out of blood vessel walls. It differs from vitamin K1 (phylloquinone), the form found in leafy greens that mainly supports liver clotting factors; K2 is made by gut bacteria and found in fermented foods and animal products, and circulates in the body longer than K1. People take vitamin K2 supplements hoping to support bone density and arterial health, often alongside vitamin D3, since the two work together in calcium metabolism. The two common supplemental forms, MK-7 and MK-4, differ substantially in half-life and typical dose: MK-7 is dosed in micrograms and persists in circulation for days, while MK-4 clears within hours and studies using it for bone health have generally used much larger doses. Because vitamin K2 is a form of vitamin K, it can also counteract warfarin and other vitamin K antagonist anticoagulants.