Omega-3

2-4 g EPA+DHA daily for a minimum of 3 months (Abdelhamid, 2020; Elagizi, 2021; Madison, 2021; Wolters 2021)

• Cardiovascular disease and all-cause mortality: 2020 Cochrane review of 86 RCTs (n=162,796) concluded EPA+DHA reduced coronary heart disease mortality (10%), but not overall risk of CVD (primary or secondary), or all-cause mortality, noting that high intake of EPA+DHA vs low decreased triglycerides by 15%. (Abdelhamid 2020)
• Longevity and aging: 1.25-2.5 g/day of omega-3 (n-3) supplements were given to 138 individuals for 4 months and were found to be associated with improved markers of aging, including reduced levels of telomerase (24%), cortisol (33%), IL-6 (33%), and IL-10 (26%), with a note that 2.5 g/day produced superior results to 1.25 g/day. (Madison, 2021)
• Cognitive decline: In two separate systematic reviews, n-3 supplementation was associated with improvements in episodic memory (immediate recall) (Yurko-Mauro, 2015), as well as improvements in global cognition, visual memory, and executive functioning. (Masana 2017)
• Mood: A 2021 meta-analysis found n-3 supplementation to benefit depressive symptoms regardless of severity; subgroup analyses identified possible additional benefits with lower severity (no, or mild-moderate depression), and with longer treatment duration (>12 weeks). (Wolters 2021)

Omega-3

Vitamin D

800-3000 IU per day for ~6 months (Gao 2017; Jolliffe 2021; NIH 2021)

Upper limit (UL) of vitamin D is 4,000 IU per day (NIH 2021)

• All-cause mortality: A 2017 systematic review of meta-analyses (MAs) on vitamin D found that 8 of 12 MAs showed a significant correlation between vitamin D and reduced all-cause mortality; (Rejnmark 2017) the most recent MA on D3 found a risk reduction of 11%. (Chowdhury 2014)
• Immune health: A 2021 MA of 46 randomized controlled trials (n=75,541) found that 400-1,000 IU/day of vitamin D safely reduced acute respiratory infection (ARI) risk by 8% (Jolliffe 2021); vitamin D may also play a role in autoimmune health. (Antico 2012)
• Musculoskeletal health: With regards to aging and arthritis, a 2017 MA found doses of vitamin D over 2000 IU to improve pain and function scores in knee osteoarthritis. (Gao 2017)
• Mood: A 2019 meta-analysis found an association between vitamin D and moderate effect size improvements in symptoms of major depression. (Vellekkatt 2019)
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Vitamin D

Magnesium

400 mg per day (NIH 2021a; Zhao 2019) for > 8 weeks (Mah 2021)

• Hypertension: A meta-analysis found that both serum and dietary levels of magnesium were significantly inversely associated with both coronary heart disease and cardiovascular disease overall, with effects seen between 173-457 mg per day in their model (Zhao 2019). Magnesium appears to reduce blood pressure in uncontrolled hypertensive patients at >240 mg per day. (Rosanoff 2021)
• Headaches: Magnesium has strong evidence for the prevention of migraine headaches as it was found to reduce risk by 62% in a 2020 meta-analysis. (Veronese 2020)
• Sleep: Sleep latency was found to be significantly reduced by magnesium supplementation in a 2021 meta-analysis where < 1000 mg of elemental magnesium three times per day was recommended. (Mah 2021)
• Cognitive health: A 2019 meta-analysis of observational studies showed a significant relationship between ADHD and lower serum magnesium. (Effatpanah 2019)
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Magnesium

B complex

Variable based on each B vitamin and form

• Stress and mood: B complex supplementation was found to benefit feelings of stress in healthy populations and populations “at-risk” for low mood and anxiety. (Young 2019)
• Cognitive health: B Vitamins have been shown to reduce homocysteine, and in those with elevated homocysteine, B vitamins improved global cognition, episodic memory, and semantic memory. (de Jager 2012)
• Pain: Acute low back pain may be improved through B complex supplementation as it reduced treatment duration by 50% in a 2020 meta-analysis when added to diclofenac (an NSAID). (Calderon-Ospina 2020)
• Hormonal health: B6, in particular, may improve premenstrual symptoms as a meta-analysis found an overall 2.3 fold improvement vs. placebo. (Wyatt 1999)

B complex

Ashwagandha (Withania somnifera)

600 mg per day for 8 weeks (Lopresti 2019)

• Sexual health: A 2018 systematic review noted ashwagandha was associated with enhanced sexual behavior in females, as measured by the female sexual function index (FSFI) and female sexual distress index (FSDI), and improved spermatogenesis in males. (Azgomi 2018)
• Strength training: Ashwagandha supplementation has been associated with increased muscle mass, strength, and testosterone, and reduced muscle damage and fat mass compared to placebo. (Wankhede 2015)
• Stress and mood: Increased testosterone and reduced cortisol, anxiety, and borderline depression scores were associated with ashwagandha versus placebo. (Lopresti 2019)
• Sleep: Ashwagandha was found to benefit sleep onset latency, mental alertness, sleep quality, and anxiety versus placebo. (Langade 2021)

Ashwagandha