The Best Supplements for Health

Take-home points

• There is a growing pool of evidence that citicoline and creatine supplementation can improve some aspects of cognitive function, particularly memory.
• Multivitamin supplementation can improve nutrient status and, as a result, may improve cognitive and immune function, as well as reduce the risk of death.
• Some evidence suggests that l-arginine and panax ginseng can improve erectile function in men with erectile dysfunction.
• Protein supplementation is practically useful for people that struggle to meet daily protein needs with food alone, which applies more to physically active people with higher protein needs.

Many controversial opinions surround the role of supplements in promoting health. While some people believe supplements are a scam, others happily load their cupboards with blends of ancient herbs promised to cure the worlds most common diseases. The truth, as in most cases, is somewhere in the middle. It is certainly true that most supplements on store shelves have only as much benefit as the placebo effect: when people expect to benefit from a supplement and therefore do, even if the supplement doesn’t work. However, as we will highlight in this article, there is convincing evidence that a handful of supplements are truly beneficial for specific health outcomes. And, contrary to belief, these benefits can apply not only to people with certain health conditions but also to the average person in good health.

Citicoline

Citicoline (brand name: Cognizin) is the supplemental form of a compound that we produce naturally, cytidine-5′-diphosphate (CDP) choline. Citicoline is thought to promote the synthesis and transmission of the bodies chemical messengers, called neurotransmitters, which are important for memory and attentional focus. In animal and lab studies, citicoline increases the concentration of acetylcholine within nerve cells and promotes neuronal repair,¹ as well as inhibits the death of cells associated with neurodegeneration.²

Drinks enhanced with citicoline appear to increase electrophysiological markers of mental alertness and attention after 30 minutes of consumption.³ This appears to markedly impact the self-reported or measured performance of the brain in people with some form of cognitive impairment. For example, in an analysis of seven studies of citicoline in patients with mild cognitive impairment, Alzheimer’s disease, or post-stroke dementia, all studies showed a positive effect of on cognitive functions.⁴ Similarly, in another review of the supplement, individuals with poor or inefficient memories demonstrated improvements in memory efficiency, acquisition efficiency, delayed recall, and logical memory were from citicoline treatment.⁵

Research on healthy populations without cognitive deficits is scarce but the available evidence does show some benefits for improved working memory, alertness, attention, psychomotor speed and vigilance, as well as decreased impulsivity versus placebo.^6,7 Chronic marijuana smokers that are otherwise healthy have also reported benefits with relatively high-doses (>1000mg/day).⁸ Not all studies in healthy populations report benefits, but, even in those that do not, there are still typically improvements in the subgroups of participants with relatively inefficient memories.⁹

Perhaps the most fascinating results of all with citicoline studies are its effects in cocaine users. In a study designed to examine safety and efficacy of citicoline in reducing drug-related craving, 500mg citicoline decreased self-reported cocaine craving relative to placebo in just 14 days, without notable side effects.¹⁰ When another study extended the timeframe to 12 weeks in patients with both bipolar disorder and cocaine dependence, citicoline-treated individuals had a significantly lower probability of having cocaine-positive urine at the end of the study; placebo-treated patients were 6.4 times more likely to have used cocaine than those who received citicoline.¹¹

Creatine

Creatine is a naturally occurring compound, that can either be consumed in small amounts from meat and/or synthesised from amino acids (arginine, glycine and methionine). Its main function is to immediately supply energy to tissues with increased energy demands, such as muscle and brain. Augmenting intramuscular creatine stores with creatine supplementation over several weeks leads to increased concentrations of intramuscular creatine and phosphocreatine. Increases in these substrates are associated with an attenuation of ATP degradation, heightened ATP production, and an increase in energetic output during activities.^12,13

Most of the research on creatine has been specific to exercise performance, of which creatine is one of the most studied supplements ever. Based on a recent review, creatine has consistently shown performance-enhancing benefits in short, high-intensity activities, as well as enhancing adaptations to exercise training. Benefits may also extend to endurance exercise and exercise recovery, though research is more limited and controversial. Emerging evidence in older adults also suggests that creatine may enhance the to perform daily living activities, to delay fatigue, and to improve muscle mass.^12,13

The positive effects of creatine may also extend to the brain. Similar to how creatine increases creatine stores in muscle, one study found that brain creatine increased by 8.7% following a 4-week supplementation regime.¹⁴ Better yet, based on currently available evidence, three scientific reviews tentatively suggested that creatine supplementation may improve short-term memory, working memory and intelligence/reasoning in healthy individuals, possibly with selective positive effect on individuals subjected to various kinds of stress and aging.^15,16 Not all studies are overwhelmingly positive but those that do not find significant differences between creatine versus placebo tend to use either relatively low dose (< 5 grams) or only adolescent populations.^17,18 Moreover, many researchers don’t find the potential brain benefits particularly surprising, since creatine supplementation has long been used to reverse profound intellectual disability in patients with cerebral creatine deficiency syndromes.¹⁹

Multivitamin

Multivitamin-multimineral supplements lack a universal definition but typically are those providing ≥100% of the recommended daily value of most essential vitamins and minerals. These supplements they do not provide anything that cannot be sourced from food; however, since many people do not eat a nutritionally balanced diet and fail to meet some nutrient targets, multivitamin-multimineral supplements can be used as an “insurance supplement” to “fill in the gaps”. For example, in Europe and/or the United States, there is a relatively high prevalence of deficiencies for vitamins D and E, folate, vitamin B12, magnesium, potassium, selenium throughout all age groups.^20,21

One of the potential benefits of multivitamin-multimineral supplements is brain function. In an analysis of three substudies of the largest multivitamin-multimineral trial to date (lasting 1–3 years), COSMOS, In this meta-analysis of COSMOS cognitive substudies (a large RCT lasting 1–3 years; outcome-dependent), supplementation benefitted global cognition and episodic memory.²² Results from other randomized trials in older adults are mixed, with one positive²³ and another indifferent²⁴, though importantly, they often use multivitamins but not multiminerals, therefore not meeting definitions of multivitamin-multimineral like COSMOS did.

Another potential benefit of multivitamin-multimineral supplements is improving immune health. Vitamins and minerals are known to have varied roles throughout every stage of the immune system and, likewise, in pre-clinical trials, multivitamin-multimineral supplements have shown to benefit immune cells and the overall immune response.^25,26,27,28 Studies examining hard outcomes, like the frequency and severity of infections, are more conflicting.²⁹ Some trials suggest that MMN supplementation resulted in significantly fewer episodes of infection in younger adults, and, in older adults, the mean number of days spent with infection.^30,31 While even in the same studies, the overall number of infectious episodes experienced does not significantly change.^30,31 Potential benefits seem more likely in people who are undernourished and supplement for more than six months.³⁰

Finally, and to much surprise for many people, multivitamin-multimineral supplements may even modestly reduce the risk of death and some chronic diseases. In a comprehensive review of the best available evidence, multivitamin-multimineral supplementation was associated with a significant 7% reduced risk of cancer. Although the results for all-cause mortality were not significant, they also favoured a small benefit, with the estimated range of effect being anything from a 13% reduced risk of all-cause mortality, to a 1% increased risk.³² However, in the COSMOS trial, which was possibly the strongest trial to date, daily multivitamin plus cocoa extract supplementation did not significantly change the risk of cancer, cardiovascular disease or all-cause mortality versus placebo.³³

Protein supplementation

Protein supplementation refers to powders, ready-to-drink shakes, or bars with a high protein content. The primary purpose of protein supplementation is to augment dietary protein intake, helping people to meet daily protein requirements when food alone is insufficient due to financial, convenience, or other reasons. Generally, people find it more practical and convenient to consume 20–50 grams of protein in a 250–500ml drink, or a single bar, as apposed to the preparation and cooking involved with high-protein foods such as meat, eggs and legumes.

The Institute of Medicine advises a protein intake of 0.8 g/kg/day for healthy adults, as the estimated average requirement to maintain bodily functions and general health has long been estimated as 0.66 g/kg/day.³⁴ Most people in Europe and The United States meet this recommendation, as it is relatively easy to achieve with a moderately balanced diet. However, evidence suggests that these recommendations may need to be revised, possibly up to 1.2g/kg/day for healthy sedentary adults and 1.4–2.0g/kg/day for exercising adults.^35,36,37 In fact, a couple of large health organisations already recommend 1.0–1.2 grams of protein per kilogram of body weight per day (g/kg/day) for healthy older adults.^38,39 and up to 1.5 g/kg/day for those with or at risk of muscle and bone-related diseases.⁴⁰ These recommendations are practically harder to achieve with food alone.

Evidence that protein supplementation helps to increase muscle mass and improve overall body composition is overwhelming. There are numerous demonstrations that using protein supplements either post-exercise and/or to meet higher daily protein intakes (>1.2 grams/kg bw/day) increases lean body mass and various measures of physical strength.^41,42,43 One analysis of 22 studies concluded that protein supplementation led to significantly greater gains in fat-free mass and lower-body strength in individuals participating in regular resistance exercise.^44,45 Benefits of protein supplementation extend to maintaining muscle mass while losing weight, and improving overall body composition and markers of health status in people with sarcopenic obesity. ^{46,47,48,49,50}

L-Arginine and panax ginseng

In our article on supplements and erectile dysfunction, we hinted that although most supplements likely do not work, some evidence supports the use of l-arginine and panax ginseng.

in August 2023, Gabriel Petre and his research team analysed 23 of the highest-quality studies that, in total, tested 41 active ingredients found in erectile dysfunction supplements.⁵¹ Overall, they reported that only 6 active ingredients had two positive studies (or more) to support their use in erectile dysfunction. These 6 ingredients were Eurycoma longifolia, Panax ginseng, L-arginine, Corynanthe yohimbe, Tribulus terrestris and Pinus pinaster. However, the researchers noted some concern and/or a high amount of bias for most studies supporting these active ingredients, meaning that the studies were carried out in a way that may have increased the chance of a positive result. The researchers were least concerned with the studies in support of L-arginine and Panax ginseng supplementation studies; therefore, these ingredients are deemed to have the strongest evidence in support of a benefit for erectile dysfunction.

More evidence is needed to clarify the potential benefits of these supplements for erectile dysfunction. Though, both have good safety profiles (l-arginine, up to 20 grams per day⁵²; panax ginseng, up to 3 grams per day⁵³) in doses that are considerably above those associated with improving erectile dysfunction (l-arginine, 5 grams per day; panax ginseng, 800 milligrams per day).

Please always remember that dietary supplements are not a replacement or alternative to medication. The US Food and Drug Administration (FDA) states that, “Unlike drugs, supplements are not intended to treat, diagnose, prevent, or cure diseases. That means supplements should not make claims, such as “reduces pain” or “treats heart disease”. Claims like these can only legitimately be made for drugs, not dietary supplements.” If you are confused about whether you are taking safe or effective supplements, or have an interest in using a particular supplement, please consult a health professional beforehand.

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