For best absorption and optimization of your expensive supplements take into consideration these combinations.

Iron plus Vitamin C (Ascorbic Acid)

Starting with the most well known combination of supplements and the most recommended. Elemental iron, also called non-heme iron, is best absorbed when taken with ascorbic acid. Even in dietary means, having spinach with something citrus like tomatoes or mandarin orange slices will increase your bodies absorption of iron (1). This is even more important in those who are suffering iron-deficiency anemia as well as vegans/vegetarians who aren’t getting their iron from meat sources (2). The ascorbic acid prevents iron from creating insoluble forms of itself while also changing its composition. Other factors must also be considered with iron absorption such as not taking dietary fibre at the same time or foods high in tannins.

Folate (B9) and Vitamin B12

Folate (naturally occurring in foods) or folic acid (synthetic form) supplementation can mask B12 deficiency symptoms. So with most folate products you will see small to moderate amounts of B12 listed in its ingredients, which is required by Health Canada. In cardiovascular disease (CVD) folate is important in reducing homocysteine levels which are aggravators/indicators of disease and even more so in combination with Vitamin B12 (3). When it comes to reducing the risk of cardiovascular disease it isn’t shown to be as effective. A meta-analysis of 34 851 patients showed a reduction of homocysteine levels in otherwise healthy patients but no reduced incidence of CVD in their lifetime (4). As a treatment in those who are already high risk or have a CVD, it is seen to reduce incidence of stroke and cardiovascular events (5). The importance of B12 in the absorption and storage of Folate is crucial for optimal health and many various treatments.

Curcumin with Piperine

Curcumin is a wonder molecule that is found in Turmeric root and gives the herb its bright yellow colour. Well researched in many aspects of medicine and health, it is a potent anti-oxidant and anti-inflammatory used in various health conditions such as osteoarthritis, cardiovascular disease, autoimmune disorders, diabetes, cancer and more. Curcumin is a very big molecule though, and not very well absorbed by the body and quickly metabolized, so many supplement companies have made patent versions of curcumin boasting their higher availability. One of the more simpler ways to increase absorption is through combination with piperine. Piperine is an active constituent in black pepper. The combination of black pepper and turmeric has been used for thousands of years by Indian and Asian communities. Piperine combined with curcumin has shown to increase bioavailability by 2000% than Turmeric alone, which keep in mind is a very small number to begin with (6). Most high quality line supplements that have Curcumin as a product tend to have optimal bioavailability to show significant health benefits. Turmeric or turmeric extracts on their own do not.

CoQ10 plus PQQ

CoQ10 is well known to improve heart health and blood sugar regulation in those with CVD and/or diabetes. Not only that but it is incredibly important in redox reactions in the electron transport chain. Can’t remember Grade 12 biology? It is one of the main reactions in the mitochondria, which of course are the powerhouse of the cell, providing our bodies with the high energy molecule ATP. Supporting our mitochondria with CoQ10 helps with infertility issues, cognitive decline and muscle atrophies to name a few benefits (7). A newer molecule found in many plants called PQQ is shown to increase mitochondrial count in the body, which is important for many diseases that cause destruction and decline in our important mitochondria (8). The combination of PQQ with CoQ10 has shown a drastic increase in mitochondria count due to PQQ, and function due to CoQ10, which is important in those diseases where mitochondria in the body is dysfunctional. This also includes preventing cognitive decline and in newer developments of anti-aging.

Niacin (B3) and Tryptophan

Not really a combo but more of an important duo. Niacin is a B vitamin that is often used in supplement form to help with cholesterol levels. Daily needs of niacin are fairly low but to have clinical health effects it is supplemented at high dosages. Tryptophan obtained through turkey and chicken consumption is converted to many different constituents, one being Niacin, at about 3.3% (9). Pellagra, a disease resulting from low animal protein consumption was thought to be due to tryptophan deficiency, but what wasn’t known at the time is that the lack of niacin from metabolized tryptophan was the issue. So even though we can supplement Niacin now, a majority of it comes from animal sources high in tryptophan. Those who are vegan or vegetarian should eat fortified foods or add niacin supplements to their daily routine. Tryptophan is also a large contributor of 5-HTP in the body, the precursor to awake and sleep hormones Serotonin and Melatonin depending on the time of day. Supplementing both together doesn’t necessarily increase health outcomes, but each are used separately in various treatments.

BCAAs and Whey

Many avid gym goers most likely know this combination, as these two supplements are rumoured for optimal muscle growth in the way of muscle protein synthesis. BCAAs are branched chain amino acids consisting of Leucine, Isoleucine and Valine, the main regulators of protein synthesis in the body aka muscle gains over time with exercise. Alone they have not shown significant increases in the body’s natural protein synthesis processes, as there are rate-limiting steps with the availability of these amino acids and amount of protein broken down with exercise (10). During exercise there is already significant amounts of released amino acids to help with reconstructing those muscles. BUT, when there is additional protein circulating by means of supplementation (Whey or other animal based proteins), BCAAs can help utilize those extra proteins into muscle synthesis more optimally, even at small doses (11). It is even seen that at smaller doses of Whey (6-8g) we see BCAAs work more effectively, while at 25g of Whey protein, BCAAs show no benefit. Most likely due to how fast our body can synthesize proteins into muscle with these rate-limiting steps.

Zinc and Copper

Zinc deficiencies and its prevalence has been widely debated as zinc is found in abundance in some foods. Yet we still see symptoms of zinc deficiency in North America especially in older populations (12). This mineral has implications in immune health, acne, hormone regulation and much more. More on zinc and zinc deficiency can be read here. The reason copper is important alongside supplementation of zinc is that high dosages over 4 months or more can cause a copper deficiency leading to a ballad of health problems (13). Copper and zinc compete for the same absorption sites in the small intestine and both take some time to be absorbed by those sites. The amounts of zinc needed for such complications is over 50mg. There are many supplements that can cause issues when taken in high dosage over long periods of time. So it is best to ask a health professional who is familiar with both natural supplements and your health history about recommended dosages.

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References:
(1) Hallberg L, Brune M, Rossander L. The role of vitamin C in iron absorption. Int J Vitam Nutr Res Suppl. 1989;30:103-108.

(2) Li N, Zhao G, Wu W, et al. The Efficacy and Safety of Vitamin C for Iron Supplementation in Adult Patients With Iron Deficiency Anemia: A Randomized Clinical Trial. JAMA Netw Open. 2020;3(11):e2023644.

(3) Lee BJ, Huang MC, Chung LJ, et al. Folic acid and vitamin B12 are more effective than vitamin B6 in lowering fasting plasma homocysteine concentration in patients with coronary artery disease. Eur J Clin Nutr. 2004;58(3):481-487.

(4) Li J, Li B, Qi J, Shen B. [Meta-analysis of clinical trials of folic acid, vitamin B12 and B6 supplementation on plasma homocysteine level and risk of cardiovascular disease]. Zhonghua Xin Xue Guan Bing Za Zhi. 2015;43(6):554-561.

(5) Wang Y, Jin Y, Wang Y, et al. The effect of folic acid in patients with cardiovascular disease: A systematic review and meta-analysis. Medicine (Baltimore). 2019;98(37):e17095.

(6) Shoba G, Joy D, Joseph T, Majeed M, Rajendran R, Srinivas PS. Influence of piperine on the pharmacokinetics of curcumin in animals and human volunteers. Planta Med. 1998 May;64(4):353-6.

(7) Hernández-Camacho JD, Bernier M, López-Lluch G, Navas P. Coenzyme Q10 Supplementation in Aging and Disease. Front Physiol. 2018;9:44. Published 2018 Feb 5.

(8) Chowanadisai, W., Bauerly, K.A., Tchaparian, E., et al. (2010). Pyrroloquinoline quinone stimulates mitochondrial biogenesis through cAMP response element-binding protein phosphorylation and increased PGC-1alpha expression. J Biol Chem, 285(1), 142-52.

(9) Grace A. Goldsmith, M.D. Niacin-Tryptophan Relationships in Man and Niacin Requirement. The American Journal of Clinical Nutrition, Volume 6, Issue 5, September-October 1958, 479–486.

(10) Wolfe RR. Branched-chain amino acids and muscle protein synthesis in humans: myth or reality?. J Int Soc Sports Nutr. 2017;14:30. Published 2017 Aug 22. doi:10.1186/s12970-017-0184-9

(11) Churchward-Venne TA, Burd NA, Mitchell CJ, et al. Supplementation of a suboptimal protein dose with leucine or essential amino acids: effects on myofibrillar protein synthesis at rest and following resistance exercise in men. J Physiol. 2012;590(11):2751-2765.

(12) Prasad AS, Halsted JA, Nadimi M. “Syndrome of iron deficiency anemia, hepatosplenomegaly, hypogonadism, dwarfism and geophagia.” Am J Med. 1961;31:532–546.

(13) Duncan A. et al. “The risk of copper deficiency in patients prescribed zinc supplements.” J Clin Pathol. 2015;68(9):723-5.