Research Recap on Some Favorite Foundational Nutraceuticals

The public awareness on nutrition has been palpable over the past few years, with people showing interest in taking charge of their health. The collective goal of achieving better health has naturally motivated people to learn more about improving their diets and using nutraceuticals. Nutraceuticals should complement a nutrient-dense diet and not replace food altogether. A balanced diet—mostly made of unprocessed, whole foods, which ideally is generally free of additives and toxic agricultural chemicals—provides a significant amount of macro- and micronutrients that are essential for maintaining good health. ^1,2

Thoughtful consideration must be done before deciding if relying on diet or using nutraceuticals therapeutically, as there are certain nutrients that people may benefit from consumption. One must think about health conditions that may limit the absorption of nutrients, such as inflammatory bowel disease, hypochlorhydria, bile-acid malabsorption, and chronic infectious diseases. Some natural and normal physiological states, like pregnancy and aging, may also increase nutritional requirements and needs. It is crucial to factor the manufacturing process and additives included in food that may significantly affect how one may react to foods. ^3,4

Here is a recap of foundational nutraceuticals, general information on bioavailability, and new research. Dosing suggestions below are listed as recommended dietary allowances (RDAs), adequate intakes (AIs), and tolerable upper intake levels (ULs) per Health Canada references.

 Vitamin D₃

Vitamin D₃ (cholecalciferol) is a fat-soluble vitamin and functions as a prohormone (hormone precursor). Vitamin D promotes bone mineralization and remodeling by enhancing the intestinal absorption of calcium and phosphorus, plays a role in neuromuscular function and insulin regulation, influences cellular growth and differentiation, and modulates immune function. Vitamin D₃ occurs naturally in fish and in small amounts in a few other foods (e.g., cheese, egg yolk, beef liver). ^5,6

Bioavailability

As vitamin D is biologically inactive, it goes through two hydroxylation reactions; first in the liver to form 25 hydroxy vitamin D (25(OH)D), and second in the kidney to produce 1,25 dihydroxyvitamin D (1,25(OH)₂D), which is the biologically active form of vitamin D and functionally a steroid hormone. In the skin, provitamin D₃ (7 dehydrocholesterol) is converted to vitamin D₃ after exposure to sunlight or other sources of ultraviolet light. Vitamin D₂ (ergocalciferol) is produced by solar irradiation of provitamin D₂ (ergosterol), a sterol present in fungi. Vitamin D becomes an essential nutrient when sunlight exposure is inadequate. Food sources may not provide enough to treat deficiency. ^7,8,9,10

Dosing

Current recommendations call for adults ages 19–70 to get 600–4,000 international units (IU) of vitamin D per day, and 800 IU per day starting at age 71. ¹¹

New Research

Vitamin D deficiency is associated with the extent of the risk of mortality from cancer, cardiovascular disease, and respiratory diseases. The risk for death decreased steeply with increasing concentrations until 50 nmol/L, whereas odds of all-cause mortality were estimated to increase by 25% for participants with a measured 25(OH)D concentration of 25 nmol/L compared to 50 nmol/L. ¹² Supplementation of vitamin D also appears to alleviate depressive symptoms in adults as seen in randomized placebo-controlled trials in different populations—those with depression, the general population, and those with various physical conditions. Dosing varied among the studies but typically were 50–100 micrograms daily (resp. 2,000 and 4,000 IU). ¹³ There also seems to be a protective effect of antenatal cholecalciferol supplementation. Babies had a lower risk of developing atopic eczema in their first year of life if their mothers took 1,000 IU of vitamin D daily from 14 weeks of pregnancy until delivery. ¹⁴ A new observational study from the University of South Australia also demonstrated a direct link between dementia and vitamin D levels. 25(OH)D had an inverse association with white matter hyperintensity volume, and deficiency was associated with an increased risk of dementia and stroke. In some populations, dementia cases (as much as 17%) may be mitigated by correction to normal vitamin D levels (50 nmol/L).¹⁵

Vitamin _K₂

Vitamin K is a fat-soluble vitamin and the general term for a group of structurally related compounds with a 2 methyl 1,4 naphthoquinone nucleus that have antihemorrhagic activity. Vitamin K₂ is involved in calcium metabolism, particularly by guiding calcium towards the skeletal system and diverting from arterial calcification. Vitamin K is used in the treatment of vitamin K deficiency caused by broad-spectrum antibiotics, cephalosporins, and prednisone. It is involved in blood coagulation, bone metabolism, prevention of vessel mineralization, and regulation of various cellular functions. ^16,17,18

Phylloquinone (vitamin K₁) is found in green leafy vegetables and vegetable oils. Low levels of phylloquinone and modest amounts of menaquinones (vitamin K₂) can be found in meat, dairy, and eggs. Menaquinone 7 (MK 7) is the fraction with the highest bioavailability and activity of menaquinones forming vitamin K₂. Fermented soybeans (natto) contain high amounts of menaquinones. ¹⁹

Bioavailability

Low dietary vitamin K intake or a failure to consume enough fat with vitamin K–rich foods may contribute to suboptimal vitamin K status. The hydrogenation of vegetable oils also affects the overall effect of vitamin K activity on bone formation. Vitamin K content in foods largely depends on bacterial strains used in manufacturing and fermentation conditions. ^20,21

Dosing

Current recommendations call for adults ages 19 and above to get 90–120 IU of vitamin K per day. ²²

New Research

In a double-blind, randomized clinical trial involving 244 healthy postmenopausal Dutch women, vitamin K₂ taken at a nutritional dose (180 μg as MK 7) for three years brought substantial benefits in inhibiting age-related stiffening of arteries, especially in women having a high arterial stiffness. MK 7 not only suppressed arterial stiffening but also resulted in an unprecedented statistically significant improvement of vascular elasticity. Vitamin K₂ supplementation has been associated with improved cardiovascular outcomes and potentially improved survival among cardiac patients. Intake has also been inversely associated with cancer incidence and mortality in observational studies. Vitamin K in cancer cells functions in the activation of the steroid and xenobiotic receptor (SXR) and in the regulation of oxidative stress, apoptosis, and autophagy. ²⁵

Vitamin B₁₂

Vitamin B₁₂ is a water-soluble vitamin that is naturally present in some foods, added to others, and available as a dietary supplement and a prescription medication. Compounds with vitamin B₁₂ activity are called “cobalamins” for their cobalt content. Vitamin B₁₂ plays a role in DNA synthesis, red blood cell formation, and homocysteine metabolism. It is involved in the functioning of the nervous system and immune system. ^26,27,28

Bioavailability

Methylcobalamin and 5 deoxyadenosylcobalamin are the metabolically active forms of vitamin B₁₂. Hydroxycobalamin and cyanocobalamin become biologically active after they are converted to methylcobalamin or 5 deoxyadenosylcobalamin. Vegan diets contain very little vitamin B₁₂ (average 0.3–0.4 μg/day). Low vitamin B₁₂ status is also common in elderly populations, those with pernicious anemia, people with chronic digestive issues, and people who are using certain medications on the long term (e.g., acid-suppressive therapy, aspirin, oral contraceptives, metformin). Low vitamin B₁₂ intakes are also likely in people of low socioeconomic status, women, and non Hispanic Black Americans. ²⁹

Dosing

Current recommendations call for adults ages 19 and above to get 2.4 mcg of vitamin B₁₂ per day. ³⁰

New Research

A Burkinabe study looked at the effect of vitamin B₁₂ status and pediatric development. Vitamin B₁₂ deficiency in infants leads to poor motor development and anemia (impaired erythropoiesis). This finding emphasizes the gravity of how short-term food relief is not sufficient in improving vitamin B₁₂ stores in children. ³¹ An interesting study on Caenorhabditis elegans (roundworm) models was done to understand how early-life B₁₂ status may impact adult health, with the intent of potentially connecting B₁₂ deficiency in infants and the associated increased propensity to develop obesity and diabetes later in life. Early-life B₁₂ deficiency in adult C. elegans worms causes increased lipogenesis, lipid peroxidation, and ferroptosis-induced germline defects, resulting in increased adiposity and infertility later in adulthood. Repressing lipogenesis or ferroptosis were suggested mechanisms in addressing infertility. ³²

Iron

Iron is a mineral essential for the delivery of oxygen to the tissues as a component of hemoglobin. Iron in myoglobin supports musculoskeletal metabolism and connective tissue function. Iron is also involved in neurological development, cellular functioning, synthesis of some hormones, thyroid, and immune function. ^33,34,35

Bioavailability

Heme and non heme iron are the main forms of dietary iron. Plants and iron-fortified foods contain non heme iron only, whereas meat, seafood, and poultry contain both heme and non heme iron. Heme iron has higher bioavailability than non heme iron. The bioavailability of iron is approximately 5–12% from vegetarian diets, compared to approximately 14–18% from mixed diets that include substantial amounts of meat, seafood, and vitamin C which enhances iron absorption. ^36,37,38

Bioavailability

Current recommendations call for adults ages 19 and above to get 8–45 mg of iron per day. ³⁹

Conclusionh

A multivariate genomic scan for health span, parental lifespan, and longevity—data from more than a million people—implicates 10 genomic loci (near FOXO3, SLC4A7, LINC02513, ZW10, and FGD6) associated with effects on cardiovascular disease and activities of aging, such as response to DNA damage, apoptosis, and homoeostasis, and interestingly iron metabolism. This international study suggests that maintaining healthy levels of iron in the blood could be a key to aging better and living longer. ⁴⁰

New Research

The science, even for basic vitamins and minerals, continues to evolve, as more evidence is gathered on the long-term effects of these essential nutrients on our health. The idea of deficiency versus sufficiency, based on generalizations for all, is no longer serving the wellbeing. This knowledge helps to deepen the understanding of health and longevity based on individual characteristics, disease states, and the environment. These all impact how much nutrients we may need in any given period of our life.