Introduction

Supplements have been pushed on every single social media platform to promote health and well-being. Most of these sources are misrepresenting these supplements and damaging the community that accurately represents the appropriate use of these widely-accessible molecules. In addition to the misrepresentation, the stores and online inventories can quickly overwhelm not only the general population but also knowledgeable individuals. The purpose of this blog post is to provide you with the most valuable and beneficial molecules so that you can start your own supplement protocol that benefits your body and brain. 

Supplementation should be precisely what the name implies, an addition of something to achieve completion. The diet of any individual taking supplements should be conducive to their supplement regimen. Their diet should be rich in nutrients. With a few exceptions, supplements should not be taken because someone doesn’t want to eat a good diet. 

A supplement regimen will not outperform a lack of exercise and a poor diet. Daily cardiovascular exercise should still be performed along with regular resistance training to improve all aspects of health. 

These supplements should be approved by a physician prior to use, and proper documentation regarding administration and outcomes should be performed. I am not a licensed medical doctor. Nor is this a complete list of beneficial compounds; instead, this list is a great starting place for people looking to optimize their nutrient intake.

Omega-3 fatty acids are commonly supplemented in the form of fish or krill oil. Despite their wide availability, the dose in varying products is suboptimal. A daily dose consisting of 2,000 mg of eicosapentaenoic acid (EPA) and 1,000 mg of docosahexaenoic acid (DHA) is supported by the literature. A 2,000 mg daily dose of EPA is conducive to a variety of health markers, including serum methionine and cysteine levels. EPA supplementation has been shown to improve inflammatory markers, alleviate some symptoms of depression, improve pregnancy outcomes, and alleviate some symptoms of type 2 diabetes mellitus. EPA supplementation also seems to improve strength when performing resistance exercise, thus promoting skeletal muscle health. Other studies have demonstrated that EPA promotes cardiovascular health. While this is the case in some studies, the topic is controversial. DHA supplements, found in fish oil in combination with EPA, are beneficial for cognition and have been demonstrated to improve memory and reaction time in young adults.

Other studies hint at the fact that adequate intake of omega-3 fatty acids promotes neuronal growth and survival. Omega-3 fatty acid supplementation also seems to increase levels of peripheral brain-derived neurotrophic factor, improve white matter integrity, and increase gray matter volume in the brain. Altogether, proper supplementation of both EPA and DHA provides beneficial effects on the brain which may potentially alleviate symptoms of many diseases, including aging. 

Magnesium is an element found naturally in pumpkin seeds, almonds, and dark leafy vegetables. Although the recommended daily intake is only 400 mg, nearly half of all Americans do not reach this value. Furthermore, exercise, pregnancy, and labor-intensive jobs can increase magnesium usage and excretion by the kidneys, thus requiring a higher intake from dietary sources. Magnesium is a required cofactor for many enzymatic reactions in the body, including ATP synthesis and glycolysis. Magnesium also plays a role in bone integrity and muscle relaxation, which makes it an element of increasing importance in the weight-lifting community. Magnesium can interact with cells in the parathyroid gland to regulate parathyroid hormone production, which will impact calcium levels, bone density, and vitamin D levels. Magnesium also plays a crucial role in the brain where it binds to N-methyl-d-aspartate receptors (NMDAr) and prevents the neuron from being excited by the neurotransmitter glutamate. Therefore, magnesium can act to prevent excitotoxicity, or death from too much excitatory (glutamate) signaling. A 2022 meta-analysis looking at magnesium supplementation on inflammatory markers concluded that magnesium supplementation significantly reduced C-reactive protein (CRP) and other inflammatory markers, including interleukin-1. 

Supplementing magnesium has also been demonstrated to improve blood glucose regulation in type 2 diabetes mellitus patients. Notably, magnesium supplementation improved HbA1C and insulin resistance in diabetic patients. Although there are many uses for magnesium, it depends on the formulation. For example, magnesium oxide and magnesium citrate are poorly bioavailable and are used in many laxatives to promote bowel movement. On the other hand, magnesium glycinate is more bioavailable but does not permeate the blood-brain barrier. Therefore, it can be used to effectively raise serum magnesium levels with minimal brain impact. Another form of magnesium, namely, magnesium threonate, is highly bioavailable and permeates the blood-brain barrier, thus making it effective at raising magnesium levels in cerebrospinal fluid. There is increasing evidence that magnesium threonate can drastically improve symptoms in many neurological disorders, including Parkinson’s and Alzheimer’s. Magnesium threonate also seems to promote neuronal survival when compared to other forms of supplemental magnesium. 

A good guideline for magnesium supplements would be to evaluate your magnesium intake on a daily basis. If you eat the same foods each day, log your diet into “cronometer” and evaluate your daily intake of magnesium. If this value is below 400 mg, a magnesium threonate supplement of 200 mg is a good place to start. If your diet varies from day to day, starting with a baseline supplement of magnesium threonate at 200 mg ensures you are receiving an adequate amount of magnesium. Even though magnesium threonate at 200 mg is beneficial even when the 400 mg recommended daily intake is met, pushing the upper limits of magnesium intake requires an increase in calcium intake, which can be achieved by adding a cup of almond milk to one’s diet. 

A reminder that a conjugated form of magnesium, such as magnesium threonate, may be labeled as 2,000 mg magnesium threonate. This is not the same as 2,000 mg magnesium because the threonate molecule has mass. Be sure to look for a label using 200 mg from X mg of magnesium threonate. 

Vitamin D3 (Vitamin D) has gained a lot of notoriety in recent years thanks to its ability to act as a hormone throughout the body. Vitamin D not only impacts the immune system but also bone homeostasis, blood glucose regulation, and inflammation. Unfortunately, many people in the United States live with vitamin D deficiency because, in order to meet a daily intake of 600 IU, a lot of fish must be consumed. In recent years, vitamin D deficiency has been correlated with many diseases and disorders, including inflammatory bowel disease, rheumatoid arthritis, and multiple sclerosis. 

Sunlight exposure can stimulate vitamin D production with adequate sunlight exposure, depending on location, ranging from 15 minutes to an hour. Between the range of sunlight exposure and UV intensity variation throughout the week, a vitamin D supplement may provide a baseline so that daily intake is sufficient despite the weather and behavioral habits. Although sunlight exposure in the morning is crucial for the circadian clock, dopamine production, and cortisol release, it may be impractical for vitamin D production due to lower UV intensity in the early morning, thus requiring more time in the morning. 

Many clinical trials are being conducted to test vitamin D supplementation against multiple disease states. One of which was inflammatory bowel disease, which seemed to significantly improve scores of IBD severity. Another meta-analysis found that vitamin D supplementation has found that vitamin D supplementation significantly reduces cancer-related deaths, thus making it a powerful cancer-fighting drug. Likewise, a meta-analysis looking at vitamin D and COVID-19 severity found that vitamin D supplementation was associated with improved clinical outcomes. Although vitamin D seems to be a wonder supplement, many myths are floating about, including vitamin D and cardiovascular health, which in truth, vitamin D supplementation does not improve cardiovascular disease. 

Vitamin D is crucial for many biological processes, and a quick glance through the literature proves that a daily supplement of 600-5000IU can alleviate vitamin D deficiency and its associated symptoms. 

Vitamin K is a fat-soluble vitamin found in two main forms known as vitamin K1 and vitamin K2. Vitamin K1 is found in dark leafy vegetables, while vitamin K2 is found mainly in poultry and eggs. Both vitamin K1 and vitamin K2 are used by the body and referred to collectively as vitamin K, although vitamin K2 seems to be more biologically active and much of the dietary vitamin K1 is converted to vitamin K2. Vitamin K is crucial for synthesizing four coagulation factors in the coagulation cascade, thus making it vitally important for cardiovascular health. Until recently, little information regarding vitamin K’s impact on other systems was unknown. Vitamin K is also important for bone health, and chronic insufficiency increases one’s chance of osteoporosis and other age-related diseases. 

Other functions of vitamin K include regulating the vasculature. It was found by a 2018 meta-analysis that vitamin K supplementation significantly reduced vasculature calcification. This reduction can be crucial for promoting vascular health and reducing the chance of developing atherosclerosis. Although limited evidence is available on the effects of vitamin K supplementation, sub-clinical vitamin K insufficiency may be detrimental to cardiovascular and kidney health. Therefore, an 80-120 mcg vitamin K2 supplement can prevent chronic insufficiency. 

The gut microbiota refers to the abundance of microorganisms that live within the gut. This environment interacts with the body in an impactful way, such that an unhealthy population of bacteria can have detrimental effects on cognition and health. These bacteria and other microorganisms can consume undigested foods and release byproducts that enter circulation and interact with cells all over the body. Therefore, having a healthy population is crucial for maintaining health. This research, albeit not novel, has been widely ignored until recently when new research has associated dysregulated microbiota with neurological disorders such as depression and Parkinson’s disease. 

Diet and exercise are the main factors affecting the gut microbiota. A poorly balanced diet, poor in vitamins and minerals, causes a change in species ratio, which impacts the production of byproducts that impact our body. Even so, a good diet and exercise regimen can be combined with a probiotic formulation to drastically improve gut health. The market for probiotics is flooded, with many companies creating unregulated/untested products with unsupported bacterial strains and ratios. As a general consumer, selecting a probiotic that is scientifically supported can be overwhelming.

In a randomized controlled trial, a probiotic supplement enhanced cognition in a stressful environment, suggesting that gut microbiota has a direct impact on how the brain handles stress. In a pilot study, probiotic supplementation was also demonstrated to improve decision-making and impulsivity. Yet another study looking at a combination of probiotic supplementation and inulin (prebiotic) improved a variety of inflammatory markers, anxiety, and depression in coronary artery disease patients. Probiotic and prebiotic supplementation is a promising tool for promoting overall well-being. Although the research is relatively new, there have been few reports of adverse side effects. 

The strains in probiotic supplements can differ quite drastically, thus making the market overwhelming. Strains from various studies have been pulled and laid out in the chart below for easy access. 

Supplements are powerful tools when used in conjunction with a balanced, nutrient-dense diet, proper exercise routine, and quality sleep. They should not be taken as the primary source of intake, with a few exceptions such as vitamin D and omega-3 fatty acids. These molecules play vital roles in the body, and in recent years, the literature has supported the notion that the supplementation of these select molecules can benefit the consumer. These molecules are omega-3 fatty acids, namely EPA and DHA, vitamin D, magnesium threonate, vitamin K, and a probiotic and prebiotic formulation. While these are not the only supplements that are useful, they are widely accessible with a vast amount of literature supporting their use as supplements. Along with this, these supplements rarely cause side effects. Of course, there are many other supplements that are recommended. However, the molecules previously described have scientific evidence for their efficacy and may not be known to the general public. Future posts will cover more supplements and their respective efficacy. 

Literature cited