💊Supplementation and micronutrient protocol

This page covers high-yield, evidence-based supplementation protocols.

Last updated: May 12, 2024

Conflicts to declare: None. Please remember to consult with a healthcare provider prior to undertaking any of the protocols available here.

This protocol is under active development.

The Big Picture:

What's the purpose of a supplementation and micronutrient protocol?

• Broadly speaking, there are three potential reasons for supplementation:

  • To correct a pre-existing deficiency.

  • To maintain an optimal micronutrient level or to prevent a new deficiency due to environmental conditions (e.g. lack of sunlight in northern climates requires most of us to take Vitamin D) or dietary conditions (e.g. a vegan diet requires some supplementation such as Vitamin B12).

  • To enhance performance (cognitive performance or physical performance).

  • To improve longevity or reduce mortality.

What's a general framework for thinking about the evidence for and against supplements?

• The first principle to understand is that human physiology is a complex system. This means that simple intuitions that we have about nutritional deficiency do not necessarily cleanly map onto reality and actual outcomes.

• Consider the widely-held belief that multivitamins are an effective tool for preventing (or correcting) a broad spectrum of vitamin & micronutrient-related deficiencies. Large studies have actually shown that multivitamin supplementation does not appear to be effective and may even be harmful in some cases.

• A large study in 2013, for example, demonstrated no cognitive benefit to multivitamin supplementation in older men.

• The second principle to understand comes down to another common problem that people run into: over-extrapolating from small, statistically under-powered studies. In general, it has been persuasively argued that most published medical research is false. This is because of systemic issues in scientific publishing, such as publication bias, low sample sizes, and poor statistical methodolgy. The burden of proof comes down to high-quality evidence, and our standard of evidence should be high.

• The third principle is the sum of the first two: we believe that supplement stacks should be weighted according to the quality of evidence. This means, simply, that the strength of the recommendation should match the strength of evidence. This almost instantly eliminates a huge swath of common supplement stacks which contain a very high numberb of supplements, most of which have a weak evidentiary base.

Supplements we currently recommend:

Vitamin D - 2000 IU per day Strong Recommendation

• Rationale:

  • Maintenance of an optimal level: Vitamin D is a crucial nutrient and hormone vital for overall health and plays a significant role in longevity. It supports bone health by aiding calcium absorption and has broader effects, including muscle strength enhancement, inflammation reduction, and immune function improvement. Research indicates that vitamin D influences longevity genes and may impact aging processes and age-related diseases such as cancer, heart disease, and cognitive decline. Vitamin D is also utilized and correlated with immune function. Maintaining adequate vitamin D levels, through sunlight exposure, diet, or supplementation, could be beneficial for extending lifespan and improving health span, underscoring its importance beyond just bone health.

• Dosing:

  • Canadian osteoporosis guidelines discuss 1,000 IU/day as a target dose with an upper daily bound of 2,000 IU/day (assuming no known deficiency).

  • In the absence of a measured deficiency, dosing levels above 4,000 IU/day are of particular concern due to the risk of kidney damage with long term supplementation.

  • Based on a study from Osteoporosis International, we recommend 2,000 IU/day, with potentially higher doses depending on your blood levels.

  • This higher dose also accords with a healthy aging study in Europe also used a 2,000 IU/day dose as well.

Supplements under literature review:

Omega-3

• Rationale: Reduction in mortality and for maintaining overall brain health and cognitive performance.

  • The latest Canadian Cardiovascular Society 2021 guidelines do not recommend omega-3 supplementation for the purposes of preventing cardiovascular disease based on lack of evidence for benefit.
  • Conversely, another large study has found that Omega-3 levels are inversely associated with all-cause mortality. This study, among authors, has been cited by Rhonda Patrick as part of her overall argument in favour of Omega-3 supplementation.
  • Conversely, data has accumulated to suggest that Omega-3 supplementation is good for maintaining cognitive health from middle age onward.

  • In 2002, a study about 2,000 people, suggested that "higher omega-3 fatty acid concentrations are related to better brain structure and cognitive function in a predominantly middle-aged cohort free of clinical dementia."
  • A small study in 2023 with a mean patient age of 76 years found that Omega-3 levels were positively associated with "better memory, processing speed, and structural brain measures."
  • A 2018 review indicated that Omega-3 supplementation could be useful for maintaining brain health and summarized a number of small studies in Table 2.
  • Under review.

• Dosing and formulation:

  • Under review.

Creatine

• Rationale: Numerous. (Muscle-building & strength-building benefits are already well established and well known).
• Under review: Cognitive benefits, particularly in vegans and vegetarians who are not eating meat as part of their diet. Evidence for benefit in vegetarians is stronger than it is for non-vegetarians. However, evidence for cognitive

Magnesium

• Rationale: Multiple potential indications. Under review

• For reduced inflammation: A 2022 meta-analysis of 17 randomized controlled trials (RCTs) found that magnesium supplementation significantly decreased serum C-reactive protein (CRP), a marker of inflammation, and increased nitric oxide levels.
• For glycemic control: A national survey of Canadians found associations between higher serum magnesium concentrations and lower prevalence of diabetes, poor glycemic control, and insulin resistance.
• For insomnia: "This review confirms that the quality of literature is substandard for physicians to make well-informed recommendations on usage of oral magnesium for older adults with insomnia. However, given that oral magnesium is very cheap and widely available, RCT evidence may support oral magnesium supplements (less than 1 g quantities given up to three times a day) for insomnia symptoms."

Various supplements for vegan diets

• Under review.

• "Veganism is also associated with low intake of vitamins B2, (B3), B12, D, iodine, zinc, calcium, potassium, selenium," however, the same study noted that "low micro- and macronutrient intakes are not always associated with health impairments." This folds into the broader question of whether or not asymptomatic micronutrient deficiencies lead to suboptimal health and performance (i.e., not just disease).

Andrew Huberman's sleep supplement protocol

• 50 mg of apigenin under review

• 300-400 mg of magnesium threonate or bisglycinate covered under 'Magnesium' above

• 200-400 mg of theanine under review

Disclaimer: The information provided on this page is for general informational purposes only and does not constitute the practice of medicine, nursing or other professional health care services, including the giving of medical advice, and no healthcare-provider/patient relationship is formed. The content of this article is not intended to be a substitute for professional medical advice, diagnosis, or treatment and the use of this information is provided. Prior to taking any action based on the information on this page, you should speak to your licensed healthcare provider. Our licensed PHC-Nurse Practitioner coaches can assist you with individualized implementation of this protocol and others.