Study Authors: Eugenie Jumai’an (PhDc Chemical and Biomolecular Engineering), Gustavo Carrizo (PhDc, Immunology), Yu-Chiao Lin (MS Healthcare Management), Prabhu Akhil Minumula (MS Engineering Management), The Johns Hopkins University
Vitamins and minerals were major scientific achievements in how we approach disease, health, and wellness. Experimental physiology using in vivo models played a vital role in research on nutrition and greatly helped people suffering from vitamin deficiencies.In this article, we review supplements used in Hello Health® products that contain vitamins and minerals, specifically in Mighty Might™, Belly Great™, Happy Organic Vitamin B-12, Happy Calm Magnesium Glycinate, and Happy Cognition and Heart Omega-3. We aim to show how state-of-the-art scientific literature supports the health and wellness benefits of vitamin B-12, vitamin D3, Folate, phosphatidylserine, magnesium, zinc, and Omega-3.
Background on Vitamin B12 (Cobalamin)
Vitamin B12 is a water-soluble vitamin, non-toxic in humans and because we don’t produce it is important to be consumed with the diet.
Natural sources of Vitamin B12
Vitamin B12 is found naturally in a wide variety of animal foods, and manufacturers add it to some fortified foods. Plant foods have no vitamin B12 unless they are fortified. You can get recommended amounts of vitamin B12 by eating a variety of foods including the following: Fish, meat, poultry, eggs, milk, and other dairy products contain vitamin B12, Clams and beef liver are some of the best sources of vitamin B12.
- Kids: 0.4-2.4 mcg
- Adults: 2.4 mcg
- Pregnant woman: 2.6-2.8 mcg
Why should we take Vitamin B12 Supplements?
Even though vegansare the only population group at risk of developing dietary B12 deficiency (Herbert 1996), the absorption of the vitamin may decline with age, the Food Protection Program recommended that older people attain their need of this vitamin from supplements or fortified food. Older people are at risk of developing vitamin B12 deficiency because of loss of intrinsic factor (in Addisonian pernicious anemia) or through decreased secretion of the gastric acid necessary to release the vitamin from food. People with pernicious anemia, an autoimmune disease, can’t make an intrinsic factor. As a result, they have trouble absorbing vitamin B12 from foods and dietary supplements.
How is Vitamin B12 absorbed in your body?
The absorption of dietary vitamin B12 requires its release from food by gastric acid, the formation of a complex with R-proteins and linkage to intrinsic factors secreted by the stomach. After absorption in the lower small intestine vitamin B12 is transferred to its utilization sites by three carriers, transcobalamin I, II and III.
Is Vitamin B12 Safe? Will it interact with other drugs?
Can vitamin B12 be harmful?
Vitamin B12 has not been shown to cause any harm, even at high doses.
Does vitamin B12 interact with medications or other dietary supplements?
Yes. Vitamin B12 supplements can interact or interfere with some medicines.
Here are several examples.
- Gastric acid inhibitors
People take gastric acid inhibitors to treat certain digestion problems, such as gastroesophageal reflux disease and peptic ulcer disease. These drugs can interfere with Vitamin B12 absorption from food by slowing the release of hydrochloric acid into the stomach, leading to vitamin B12 deficiency. Gastric acid inhibitors include omeprazole (Prilosec®), lansoprazole (Prevacid®), cimetidine (Tagamet®), and ranitidine (Zantac®).
Metformin is used to treat prediabetes and diabetes. Metformin might reduce vitamin B12 absorption and lower blood levels of vitamin B12.
Why do we need Vitamin B12?
One Carbon Metabolism, Vitamin B12 and Folate in Health and Disease
Methionine is an essential amino acid that contains sulfur, an important atom for many biological processes. This amino acid is used in a series of metabolic reactions that take place in the Methionine cycle where methyl groups are transferred generating new amino acids (like serine and Cysteine) with key biological implications, protein translation, regulation of oxidative stress, proliferation, etc. (Figure 1) (3)
Methionine can be recycled as well. The recycling is possible by a Methyl donation from the Folate cycle. The folate cycle relates to the Methionine cycle by Vitamin B12 metabolism.
Collectively these interconnected pathways are referred as one carbon metabolism (Figure 2) (4) Because the One carbon metabolism involves several metabolic pathways interconnected with each other, an impaired activity within one of the nodes can have a significant negative impact in the overall cell function as is commonly observed in disease contexts. (5)
Figure 1 & 2
Hello Health® Happy Organic Vitamin B12
It Is a vital nutrient that supports energy metabolism, cardiovascular health and the nervous system for greater brain health and cognitive function. It also supports the production and use of Serotonin for enhanced mood.
- About energy metabolism:
Mitochondria are the energy factory in the cell. Beta Oxidation of fatty acids (lipids) that take place in the mitochondria require a series of reactions to break down long chain fatty acids in small carbon units. These carbon units will be incorporated in the tricarboxylic acid cycle (TCA) to finally generate carbon dioxide, water and energy. When there’s a deficiency in vitamin B12, a B12 dependent enzyme can’t function properly and generates an increase in metabolic intermediates. The accumulation of intermediates ultimately inhibits the activity of a key protein, resulting in a decreased Beta oxidation. In summary, vitamin B12 influences mitochondrial energy and lipid metabolic pathways. (7, 8)
There is a possible association of vitamin B12 status with obesity and gestational diabetes (GDM) in pregnant women. The absence of B12 inhibits fatty acid oxidation which promotes lipogenesis and obesity is associated with insulin resistance. If early pregnancy B12 status is found to be independently predictive of incident GDM, such findings could potentially offer simple interventions to improve the metabolic health of pregnant women and their offspring. (9-11)
- About Cardiovascular Disease:
Elevated homocysteine levels are correlated with diseases of aging including cardiovascular disease and cognitive decline; however, clinical trials have not shown a benefit in supplemental vitamin B intake for these conditions. (12)
- Nervous system/Serotonin production/Cognition:
Presenting maternal low levels of Vitamin B12 may be a risk factor for neural tube disease (NTD). Neural tube defects are birth defects of the brain, spine, or spinal cord. They happen in the first month of pregnancy, often before a woman even knows that she is pregnant. Adding B12 to folic acid in food fortification may help prevent NTD, while at the same time reducing concern about masking B12-related neurologic disease, which can occur when fortifying with folic acid alone. (13) Another study in mice shows a clear association of NTD with the One Carbon metabolic pathway by using genetic models. (14)
Homocysteine levels (a product of the Methionine cycle) were positively correlated with obsessive-compulsive disorder scores as well as associated with cognitive decline, white matter damage, brain atrophy and dementia. The accumulation of Homocysteine is an indication of a defect in Folate cycle because in order to make Methionine, 5-MTHF is necessary (15-17)
- About Megaloblastic Anemia:
Vitamin B12 and folate deficiencies as causes of megaloblastic anemias. Anemia is a condition characterized by the low levels of circulating, red blood cells. Red blood cells are released from the marrow into the bloodstream where they travel throughout the body delivering oxygen to tissue. (18)
Vitamin B12 References
3)Kelly, B., & Pearce, E. L. (2020). Amino Assets: How Amino Acids Support Immunity. Cell metabolism, 32(2), 154–175.
4)Sanderson, S. M., Gao, X., Dai, Z., & Locasale, J. W. (2019). Methionine metabolism in health and cancer: a nexus of diet and precision medicine. Nature reviews. Cancer, 19(11), 625–637
5) Ducker, G. S., & Rabinowitz, J. D. (2017). One-Carbon Metabolism in Health and Disease. Cell metabolism, 25(1), 27–42
6) Ray JG, Wyatt PR, Thompson MD, Vermeulen MJ, Meier C, Wong PY et al. Vitamin B12 and the risk of neural tube defects in a folic-acid-fortified population. Epidemiology 2007; 18: 362–366
7) Boachie J, Adaikalakoteswari A, Samavat J, Saravanan P. Low Vitamin B12 and Lipid Metabolism: Evidence from Pre-Clinical and Clinical Studies. Nutrients. 2020;12(7):1925. Published 2020 Jun 29. doi:10.3390/nu12071925
8) Khaire A, Rathod R, Kale A, Joshi S. Vitamin B12 and omega-3 fatty acids together regulate lipid metabolism in Wistar rats. Prostaglandins Leukot Essent Fatty Acids. 2015;99:7-17. doi:10.1016/j.plefa.2015.04.006
9) Sukumar N, Venkataraman H, Wilson S, et al. Vitamin B12 Status among Pregnant Women in the UK and Its Association with Obesity and Gestational Diabetes. Nutrients. 2016;8(12):768. Published 2016 Dec 1. doi:10.3390/nu8120768
10) Yajnik CS, Deshpande SS, Jackson AA, et al. Vitamin B12 and folate concentrations during pregnancy and insulin resistance in the offspring: the Pune Maternal Nutrition Study. Diabetologia. 2008;51(1):29-38. doi:10.1007/s00125-007-0793-y
11) Knight BA, Shields BM, Brook A, et al. Lower Circulating B12 Is Associated with Higher Obesity and Insulin Resistance during Pregnancy in a Non-Diabetic White British Population. PLoS One. 2015;10(8):e0135268. Published 2015 Aug 19. doi:10.1371/journal.pone.0135268
12)Lonn E, Yusuf S, Arnold MJ, et al. Homocysteine lowering with folic acid and B vitamins in vascular disease [published correction appears in N Engl J Med. 2006 Aug 17;355(7):746]. N Engl J Med. 2006;354(15):1567-1577. doi:10.1056/NEJMoa060900
13) Ray JG, Wyatt PR, Thompson MD, et al. Vitamin B12 and the risk of neural tube defects in a folic-acid-fortified population. Epidemiology. 2007;18(3):362-366. doi:10.1097/01.ede.0000257063.77411.e9
14) Leung KY, Pai YJ, Chen Q, et al. Partitioning of One-Carbon Units in Folate and Methionine Metabolism Is Essential for Neural Tube Closure. Cell Rep. 2017;21(7):1795-1808. doi:10.1016/j.celrep.2017.10.072
15)Türksoy N, Bilici R, Yalçıner A, et al. Vitamin B12, folate, and homocysteine levels in patients with obsessive-compulsive disorder. Neuropsychiatr Dis Treat. 2014;10:1671-1675. Published 2014 Sep 9. doi:10.2147/NDT.S67668
16)Esnafoğlu E, Yaman E. Vitamin B12, folic acid, homocysteine and vitamin D levels in children and adolescents with obsessive compulsive disorder. Psychiatry Res. 2017;254:232-237. doi:10.1016/j.psychres.2017.04.032
17)Smith AD, Refsum H. Homocysteine, B Vitamins, and Cognitive Impairment. Annu Rev Nutr. 2016;36:211-239. doi:10.1146/annurev-nutr-071715-050947
18)Green R, Datta Mitra A. Megaloblastic Anemias: Nutritional and Other Causes. Med Clin North Am. 2017;101(2):297-317. doi:10.1016/j.mcna.2016.09.013
Background on Methylfolate (5-methyltetrahydrofolate/5-MTHF)
Folic acid, also known as Vitamin B9, is a water-soluble vitamin and an essential micronutrient. Folate metabolism is crucial for many biochemical processes, including nucleotide biosynthesis, mitochondrial protein translation, and methionine regeneration. (1)
5-MTHF shows several important advantages over folic acid. It displays better performance compared to folic acid in terms of plasma concentrations of folate. In addition, 5-MTHF would be a fast and ready to use metabolite. (2)
Some extra advantages of using 5-MTHF instead of folic acid:
- Reduces the potential for masking hematological symptoms of vitamin B12 deficiency,
- Reduces interactions with drugs that inhibit dihydrofolate reductase and overcomes metabolic defects caused by methylenetetrahydrofolate reductase polymorphism.
- Prevents the potential negative effects of unconverted folic acid in the peripheral circulation.
Natural sources of the Methylfolate
Folate can be found naturally in many foods. It is also added to food and sold as a supplement in the form of folic acid; this form is better absorbed than that from food sources. It can be found in Legumes, Broccoli, asparagus, eggs, beef liver, and others.
- Kids: 65-300 mcg
- Adults: 400 mcg
- Pregnant woman: 600 mcg
Why should we take Folate Supplements?
Yuxiang Zheng and Lewis C. Cantley J. Recently Reviewed the effects of folate metabolism in health and disease. Systemic folate deficiency, whether dietary, alcohol or drug induced, or due to mutations in key enzymes and transporters, invariably results in megaloblastic anemia.
The molecular basis for megaloblastic anemia has been described by defects in DNA synthesis that results in chromosome breakage, and continued cell growth without division during red blood cell production. Thus, folate metabolism plays a crucial role in hematopoiesis.
Signs of deficiency can include: megaloblastic anemia; weakness, fatigue; irregular heartbeat; shortness of breath; difficulty concentrating; hair loss; pale skin; mouth sores.
People who regularly drink alcohol should aim for increased amounts of folate daily since alcohol can impair its absorption.
How is Methylfolate absorbed in your body?
Dietary folate exists in the polyglutamate form, which must be converted into the monoglutamate form to be absorbed from the intestinal lumen.
Intestinal absorption occurs by both passive and carrier-mediated mechanisms, with the second process predominating in the proximal small intestine. Passive absorption occurs mainly at higher doses of folate. Intestinal folate transport is a saturable process with a pH optimum between 5.5 and 6.0, explaining why antacids appear to reduce folate absorption (Russell et al., 1988) Methylfolate has important advantages over synthetic folic acid – it is well absorbed even when gastrointestinal pH is altered, and its bioavailability is not affected by metabolic defects.
Is Methylfolate safe?
When obtaining folate from food sources it is extremely rare to reach toxic levels.
However, one of the possibilities is that high amounts of folate can mask Vitamin B12 deficiencies because both metabolic pathways are interconnected.
Masking occurs most often in older adults or vegans where a B12 deficiency is more likely to be present. It is recommended to stick to the lower range of folate per day because the rest will be obtained by natural sources from food. (5)
Why do we need Methylfolate?
Folate metabolism (Folate cycle)
Folate metabolism takes place in parallel in the mitochondria and the cytosol. This intercompartmental aspect of the folate cycle metabolism is very important because it supports anabolic reactions such as nucleotide synthesis as well as the methionine cycle that impacts in the translation of proteins.
When Folate is taken inside the cell it gets reduced to tetrahydrofolate (THF). The reaction with the amino acid serine produces MethylFolate (5-MTHF) and glycine. The latter already contributes to the methionine cycle and Thymidylate synthesis supporting the idea that supplementation with 5-MTHF bypasses certain enzyme deficiencies that cannot generate it from Folate. At the same time, it is a faster “ready to use” metabolite.
5-MTHF is converted to its most oxidized form “10-Formyl-THF” that will contribute to the production of nucleotides, important for cell proliferation. In the Mitochondria, 10-Formyl-THF is important to produce mitochondrial proteins. The existence of the mitochondrial compartment provides the necessary flexibility to balance cellular demands for glycine and 1Carbon units. This balance is extremely important because for example glycine is used in another metabolic pathway to generate antioxidants, as well as 1Carbon units contribute to the Methionine cycle. (6-7)
Figure 1. (From 6)
Hello Health® Belly Great™ Includes MethylFolate
Supports the immune system and helps maintain healthy digestion and bones.
- About Supporting the Immune System
Research on Hematopoiesis in mice fed with normal diet, low folate and high folate diet showed that low and high levels of Folate comprise the generation of immune cells in the Bone Marrow. The authors suggest that a high Folic acid supplementation would impact negatively in the enzymes related with Folic acid metabolism. Relevant when considering Folic acid amounts in the supplements. (8) An important remark is that, as mentioned before, Methylfolate may provide an advantage here compared with Folic acid because it doesn’t saturate the enzymes that reduce Folate to THF.
More research done studying T cells (key immune cells against pathogen infected cells and cancer cells) showed the importance of One Carbon metabolism for the correct activation, proliferation and survival of the cells.
These results make sense because of the importance of metabolic pathways that take place in the mitochondria and the cytosol to support an increased need from activated cells, being the Folate cycle one of the interconnected pathways in both compartments. A deficiency in folate therefore would reduce amounts of THF thatimpacts the production of nucleotides and oxidative stress balance. (9)
Figure 2. (From 9)
Methyl Folate References
1)Zheng Y, Cantley LC. Toward a better understanding of folate metabolism in health and disease. J Exp Med. 2019;216(2):253-266. doi:10.1084/jem.20181965
2) Scaglione F, Panzavolta G. Folate, folic acid and 5-methyltetrahydrofolate are not the same thing. Xenobiotica. 2014;44(5):480-488. doi:10.3109/00498254.2013.845705
4) Zheng Y, Cantley LC. Toward a better understanding of folate metabolism in health and disease. J Exp Med. 2019;216(2):253-266. doi:10.1084/jem.20181965
6) Zarou MM, Vazquez A, Vignir Helgason G. Folate metabolism: a re-emerging therapeutic target in haematological cancers. Leukemia. 2021;35(6):1539-1551. doi:10.1038/s41375-021-01189-2
7) Zheng Y, Cantley LC. Toward a better understanding of folate metabolism in health and disease. J Exp Med. 2019;216(2):253-266. doi:10.1084/jem.20181965
8) Henry CJ, Nemkov T, Casás-Selves M, et al. Folate dietary insufficiency and folic acid supplementation similarly impair metabolism and compromise hematopoiesis.
9) Haematologica. 2017;102(12):1985-1994. doi:10.3324/haematol.2017.171074
Ron-Harel N, Santos D, Ghergurovich JM, et al. Mitochondrial Biogenesis and Proteome Remodeling Promote One-Carbon Metabolism for T Cell Activation. Cell Metab. 2016;24(1):104-117. doi:10.1016/j.cmet.2016.06.007
Background on Plant-Based Phosphatidylserine
Phosphatidylserine (PS) is an amino acid compound that is fat-soluble and found in high amounts in the brain, where it contributes to cognitive functioning. It is a type of molecule known as a phospholipid that makes up cell membranes and is abundant in the nervous system. (1,2)
Natural sources of PS:
PS is synthesized in our bodies, but also is found in many foods accessible to vegans and non-vegans as well. It is found in soy (which is the main source), white beans, egg yolks, chicken liver, and beef liver. (3)
- Kids: 200 mg
- Adults: 200-400 mg
Why should we take PS Supplements?
Phosphatidylserine plays an important role in brain cell function, so supplementation with phosphatidylserine may protect our brain cells and promote improved cognitive function.
How is PS made and why do we need PS?
Most PS that is synthesized in our bodies, including PS made in our central nervous system (CNS) results from the PSsynthase 1-catalyzed substitution of serine for cholineon PS within mitochondria-associated membrane (MAM) do-mains of the endoplasmic reticulum (ER). Maintenance of an imbalance of PS across cell membranes is critical to cell survival since active translocation of PS to the extracellular region is a required and irreversible signal for the initiation of phagocytic engulfment of apoptotic cells.To maintain this imbalance, healthy cells in our body will use 4% of the energy molecules, ATP, to maintain this asymmetry!
Any orally supplemented PS is highly bioavailable in humans and readily crosses the blood–brain barrier. The amount of exogenous PS that is incorporated and transported increases as PS intake increases.
Is PS safe? Will it interact with other drugs?
It is thought that supplementation of up to 600mg of soy based PS for 12 weeks in elderly persons has not been associated with any adverse effects. However, side effects are more common at doses of 300 milligrams and above including: Gas, upset stomach, having trouble sleeping. However, optimal doses of phosphatidylserine have not been established for any condition. Quality and active ingredients in supplements may vary widely from maker to maker. This makes it very hard to establish a standard dose.
In terms of drug-interactions, there are no conclusive studies to show instances of phosphatidylserine adversely interacting with other medications. (7-9)
Hello Health® Mighty Might™ Includes Plant-Based Phosphatidylserine
Mighty Might™ ingredients supports the immune system and helps soothe environmental stressors, detox, and improves focus
- About Focus
PS supplementation was found to be correlated with improved focus, neurocognition, and memory in several studies.Studies show that aging of the human brain is associated with loss of neurons, decreased synthesis of ACh and other neuro-transmitters, abnormal or decreased membrane PS content, and reduced sensitivity of postsynaptic membranes to ACh. In a study on the influence of PS on Na+ + K+-stimulated ATPase and acetylcholinesterase activities of dog brain synaptosomal plasma membranes, among other clinical studies on elderly patients, supplementation with PS “increased interneuronal communication by increasing the fluidity of cell membranes, eliminating the typical age-dependent decrease in ACh release, cholinergic functioning, and cognitive problem solving”. (17-19)
In a randomized, placebo controlled clinical trial, there seemed to be a strong effect of PS supplementation on improving memory and symptoms of attention-deficit hyperactivity disorder, commonly known as ADHD. Results from this study showed that PS supplementation resulted in significant improvements in: ADHD (P < 0.01), AD (P < 0.01) and HD (P < 0.01); (ii) short-term auditory memory (P < 0.05); and (iii) inattention (differentiation and reverse differentiation, P < 0.05) and inattention and impulsivity (P < 0.05) compared to the placebo groups. This study shows that PS supplementation might be a “safe and natural nutritional strategy for improving mental performance in young children suffering from ADHD”. (20)
- About environmental stressors
There is some evidence PS may assist in reducing environmental stressors. A study on the Effects Of Phosphatidylserine On Exercise Capacity During Cycling In Active Males, a 2-week double blind trial, there was a minor correlation between PS supplementation and reducing the onset of fatigue with high intensity exercises but a notable increase in anaerobic running capacity in these athletes. (11)In another study by Baumeister et al on stress reduction, PS supplementation exhibited a minor possible stress reducing effect independent of cortisol and heart rate, although these effects seemed unreliable. (12) Moreover, double blind clinical, placebo controlled trials show that patients exhibiting symptoms of chronic depression responded to PS supplementation (100 mg three times/day, for 1–6 months) with “decreased apathy, withdrawal, and sleep disturbances and increased motivation and interest in others”. (13-16)
References for PS:
- Phosphatidylserine: quantitative EEG effects in healthy volunteers, G. Rosadini, W.G. Sannita, F. Nobili and T. Cenacchi, Neuropsychobiology, 24 (1990–1991), pp. 42-48
- Age-dependent spontaneous EEG bursts in rats: effects of brain phosphatidylserine, F. Aporti, R. Borsato, G. Calderini, R. Rubini, G. Toffano, A. Zanotti et al., Neurobiol Aging, 7 (1986), pp. 115-120
- Metabolism and functions of phosphatidylserine, J.E. Vance and R. Steenbergen, Prog Lipid Res, 44 (2005), pp. 207-234
- Cognitive decline in the elderly: a double blind, placebo-controlled multicenter study on efficacy of phosphatidylserine administration, T. Cenacchi, T. Bertoldin, C. Farina, M.G. Fiori and G. Crepaldi
- Aging Clin Exp Res, 5 (1993), pp. 123-13
- Double-blind controlled trial of phosphatidylserine in patients with senile mental deterioration, G. Palmieri, R. Palmieri, M.R. Inzoli, G. Lombardi, C. Sottini, B. Tavolato et al. Clin Trials J, 24 (1987), pp. 73-83
- Effects of phosphatidylserine therapy in geriatric patients with depressive disorders, M. Maggioni, G.B. Picotti, G.P. Bondiolotti, A. Panerai, T. Cenacchi, P. Nobile et al., Acta Psychiatr Scand, 81 (1990), pp. 265-270
- Influence of phosphatidylserine on (Na+ + K+)-stimulated ATPase and acetylcholinesterase activities of dog brain synaptosomal plasma membranes, S. Tsakiris and G. Deliconstantinos, Biochem J, 220 (1984), pp. 301-307
- Cognitive decline in the elderly: a double blind, placebo-controlled multicenter study on efficacy of phosphatidylserine administration, T. Cenacchi, T. Bertoldin, C. Farina, M.G. Fiori and G. Crepaldi, Aging Clin Exp Res, 5 (1993), pp. 123-133
- Effects of phosphatidylserine in age-associated memory impairment, T.H. Crook, J. Tinklenberg, J. Yesavage, W. Petrie, M.G. Nunzi and D.C. Massari, Neurology, 41 (1991), pp. 644-649
- Figure 1: https://www.intelligentlabs.org/what-is-phosphatidylserine/
Background on Magnesium (glycinate)
Magnesium (Mg) is an essential dietary mineral. Required for over 300 biochemical reactions (1) and over 600 enzymes in the body (2). The mineral is utilized for both nerve and muscle function in the body. Being easily soluble, it is readily available for use in the body.
Natural Sources of Mg:
Magnesium is available in plant and animal foods and in beverages. Green leafy vegetables, such as spinach, legumes, and nuts, seeds, and whole grains, are a good source of the mineral.
Dose Recommendation (3)
- Kids: 30 – 410 mg
- Adults: 310 – 420 mg
- Elderly: 320 – 420 mg
- Pregnant women: 350 – 400 mg
Why should we take Mg supplements?
Low intake of magnesium might result in the following (3):
- cardiovascular disease
- type 2 diabetes, osteoporosis
- migraine headaches
Furthermore, dietary intake of Magnesium has shown to be insufficient in the western population. 68% of Americans and 72% of French adults have been shown to consume less than recommended levels of magnesium. Moreover, the following are at high risk of Mg deficiency:
- People with gastrointestinal diseases
- People with type 2 diabetes
- People with alcohol dependence
- Older adults
How is Mg absorbed in our bodies?
Magnesium is absorbed in the small intestine through a saturable transport system and via passive diffusion through bulk flow of water. Absorption of magnesium depends on the amount taken. When the dietary content of magnesium is typical, approximately 30-40% is absorbed. Under conditions of low magnesium intake (ie, 1 mmol/d), approximately 80% is absorbed, while only 25% is absorbed when the intake is high (25 mmol/d).
Figure 1 displays the regulation of magnesium balance in humans:
Reference for Figure 1 (6)
Moreover, the absorption mechanism is depicted in figure 2. Absorption pathways. Two Mg2+ -absorbing pathways have been identified in the mammalian intestine (Figure 2). Paracellular transport involves the absorption of Mg2+ through the small spaces between the epithelial cells and is a passive mechanism. Secondly, the transcellular pathway involves the active transport of Mg21 to the blood through the interior of the epithelial cell. This second type of Mg21 transport is subject to tight regulation since the ions have to pass through two cell membranes. Though having discovered the pathways, the exact mechanism is poorly understood (6)
Figure 2. Magnesium absorption mechanism
Hello Health® Happy Calm Magnesium Glycinate
Happy Calm Bolsters the Immune System as an essential nutrient used to keep the body’s defences strong. It supports calm & relaxation, allowing for more restful sleep while promoting optimal function of the nervous, muscular-skeletal and digestive systems for increased heart health, energy metabolism, brain function and more.
- About Anxiety (1):
On consuming oral Mg supplements in 200 mg - 300 mg, in combination with Vit B6 somatic anxiety rating drops significantly in individuals (both male and female, across all age groups.
- About Negative Effects of PMS (1)
PMS is a condition that affects women which occurs on certain days of the menstrual cycle. It affects the woman’s emotions, physical health and behavior. On consuming oral Mg supplement in 200 mg dosage, there seemed to be an improvement on the quality-of-life postpartum women.
- About ADHD (7)
Magnesium is a cofactor for many enzymes and has been demonstrated to interact with many monoamine receptors relevant in ADHD pathophysiology (serotonin 5-HT1A, 5-HT2A, and 5-HT2C), noradrenergic (alpha1 and alpha 2) and dopamine (D1 and D2) receptors in mouse models. A single, double-blind placebo-controlled trial demonstrated that psychostimulants increased serum magnesium levels in ADHD after 3 weeks of treatment.
- About Cardiovascular Health (3,9)
Magnesium deficiency results in the enzyme NA-K-ATPase. In this case the sodium and calcium reach higher levels and a result increases the probability of vasoconstriction in the coronary arteries. This leads to various cardiovascular conditions such as coronary artery spasms, myocardial infarction and arrhythmias.
- About Energy Production (3)
Magnesium in your body creates energy by activating adenosine triphosphate (ATP), which is the fundamental unit of energy within the body’s cells. Without proper levels of magnesium, the nutrients that you take in through food and supplements would not be metabolized into energy.
References for Mg:
- Boyle NB, Lawton C, Dye L. The Effects of Magnesium Supplementation on Subjective Anxiety and Stress-A Systematic Review. Nutrients. 2017 Apr 26;9(5):429. doi: 10.3390/nu9050429. PMID: 28445426; PMCID: PMC5452159.
- Pardo MR, Garicano Vilar E, San Mauro Martín I, Camina Martín MA. Bioavailability of magnesium food supplements: A systematic review. Nutrition. 2021 Sep;89:111294. doi: 10.1016/j.nut.2021.111294. Epub 2021 Apr 28. PMID: 34111673.
- NIH – National institute of health (https://ods.od.nih.gov/factsheets/Magnesium-HealthProfessional/)
- King DE, Mainous AG 3rd, Geesey ME, Woolson RF. Dietary magnesium and C-reactive protein levels. J Am Coll Nutr. 2005 Jun;24(3):166-71. doi: 10.1080/07315724.2005.10719461. PMID: 15930481.
- Galan P, Preziosi P, Durlach V, Valeix P, Ribas L, Bouzid D, Favier A, Hercberg S. Dietary magnesium intake in a French adult population. Magnes Res. 1997 Dec;10(4):321-8. PMID: 9513928.
- de Baaij JH, Hoenderop JG, Bindels RJ. Regulation of magnesium balance: lessons learned from human genetic disease. Clin Kidney J. 2012 Feb;5(Suppl 1):i15-i24. doi: 10.1093/ndtplus/sfr164. PMID: 26069817; PMCID: PMC4455826.
- Nutritional Supplements for the Treatment of ADHD Michael H. Bloch, MD, MS*, Jilian Mulqueen
- Lamontagne, C., Sewell, J.A., Vaillancourt, R., & Kuhzarani, C. (2012). Rapid Resolution of Chronic Back Pain with Magnesium Glycinate in a Pediatric Patient. Journal of Pain and Relief, 2012.
- Subclinical magnesium deficiency: a principal driver of cardiovascular disease and a public health crisis James J DiNicolantonio,1 James H O’Keefe,1 William Wilson
Background on Vitamin D3 (calciferol)
Vitamin D3 is a fat-soluble vitamin. Unlike many vitamins, Vit. D3 does not commonly exist in food, so its main resource is through dermal synthesis, which largely depends on the length of sun exposure.
Natural sources of Vitamin D3:
Natural vitamin D3 people intake through dermal synthesis or diet (few kinds of natural diets still contain vitamin D3, such as cod liver oil) is biologically inactive. Vitamin D3 needs to be converted into active form by liver and kidney. (Figure 1) (1) Due to its scarcity in daily diet, many products are artificially fortified with vitamin D, including milk and infant formula.
Infants(0~1 year old):10 mcg/day
Adults(1~70 years old):15 mcg/day
Elders(>70 years old):20 mcg/day
Why should we take Vitamin D3 Supplements?
Since very few foods naturally contain Vitamin D3, human beings acquire the Vitamin D3 mainly through dermal synthesis during exposure to sunlight. Though the synthesis system shows high efficiency and is able to produce abundant Vitamin D3 with adequate sun exposure, the daily amount usually fluctuates owing to weather, season or personal schedules, and varies with individual factors such as skin type (2). Besides, prolonged sun exposure may increase disease risks like skin cancer. (3)
People may not receive enough sunlight for various reasons. For instance, the elderly or disabled people may lack sun exposure because of limited moving ability. Also, people living in the northern latitude can’t get much sunlight in the winter due to the reduced time of day. Therefore, taking Vitamin D3 supplements can be an ideal way to maintain recommended daily intake for those groups.
How is Vitamin D3 absorbed in your body?
Given that Vitamin D3 is fat-soluble, it will be incorporated into micelles and absorbed by the intestine. Disorders affecting fat absorption can simultaneously influence the Vitamin D3 level. Also, since the liver and kidney are responsible to convert dietary vitamin D3 into active form, their disorder may contribute to low Vitamin D3 levels. (4)
Is Vitamin D3 Safe? Will it interact with other drugs?
Can vitamin D3 be harmful?
The toxicity dose Vitamin D3 stays unclear, which can vary due to age or individual factors like lipid malabsorption. Intoxication of Vitamin D3 mainly results from hypercalcemia. The symptom includes confusion, polyuria, polydipsia, anorexia, vomiting, and muscle weakness. Chronic intoxication can lead to nephrocalcinosis, pain, and bone demineralization. (1)
Does vitamin D3 interact with medications or other dietary supplements?
Yes. Vitamin D3 supplements can interact or interfere with some medicines: (5)
Altered serum phosphate levels: ERDAFITINIB
Decreased systemic cholecalciferol (vitamin D) concentrations:CIMETIDINE,ORLISTAT,CHOLESTYRAMINE,MINERAL OIL,COLESTIPOL,OLESTRA
Why do we need Vitamin D3?
Bone health, immunity regulation and URTI prevention
The most common understanding of Vitamin D3 is its role on bone health. Even a layman in the healthcare field knows that Vitamin D3 and calcium are beneficial to bone. Vitamin D3 not only facilitates the absorption of calcium, but also helps maintain serum calcium and phosphate concentration. Therefore, sufficient Vitamin D3 intake can prevent bone disorders like osteoporosis. Another less known benefit of Vitamin D3 is its ability to regulate our immune systems. Studies support that Vitamin D3 supplementation may hold therapeutic promise in many diseases characterized by inflammation. (6), and Vitamin D3 deficiency is associated with greater inflammation and activated monocyte phenotypes. (7)
Vitamin D3 may help prevent upper respiratory tract infection as well. Given that Vitamin D3 plays a crucial role in immunity, many scientists try to investigate its relation to diseases. It turns out that the insufficiency or deficiency of vitamin D3 may lead to higher risk of URTI, especially those with asthma and chronic obstructive pulmonary disease. (8) Besides, vitamin D3 may also have a protective effect towards influenza A on schoolchild. (9) Hence, since cutaneous vitamin D3 synthesis is naturally weakened in the winter, when viral infections typically peak, the vitamin D3 supplement may be strongly recommended to prevent these diseases.
Hello Health® Belly Great™ Includes Vitamin D3
Belly Great™ supports the immune system and helps maintain healthy digestion and bones.
- About Supporting the Immune System
Vitamin D3 plays a vital role in immunity, and inadequate consumption may lead to increased infection rates and autoimmunity. (10) Many research supports that Vitamin D3 supplementation may hold therapeutic promise in many diseases characterized by inflammation. (11)A system review substantiates that deficiency or Insufficiency of Vitamin D3 can lead to increased risk of URTI infection, and those who experience serious deficiency but not receive single doses over a short period of time benefit most from Vitamin D3 supplement. (12)
- About Improving Bone Health
Vitamin D3 is commonly recommended to prevent osteoporosis and falls for the elderly, for it can improve the calcium absorption and avoid loss of bone and tooth. Moreover, infants who are exclusively breastfed also require Vitamin D3 supplement because human milk doesn’t contain much Vitamin D3. (Unlike market milk and baby formula, which are intentionally fortified with Vitamin D.) (13)
Vitamin D3 References:
1) Overview of vitamin D. UpToDate
2) Binkley N, Novotny R. (2007). Low vitamin D status despite abundant sun exposure., J Clin Endocrinol Metab. 2007;92(6):2130.
3) Honnavara N A. (2001). Sunlight and skin cancer. J Biomed Biotechnol. 1(2): 49.
4) Dibble JB, Sheridan P. (1984). A survey of vitamin D deficiency in gastrointestinal and liver disorders. Q J Med. 1984;53(209):119.
5) Cholecalciferol: Drug Interactions. IBM Micromedex.
6) Michelino D.R., Michele M, (2011). Vitamin D3: a helpful immuno-modulator. Immunology. 2011 Oct;134(2):123-39
7) Maura M, Katherine H.H. (2017). Vitamin D deficiency is associated with IL-6 levels and monocyte activation in HIV-infected persons. 2017; 12(5): e0175517.
8) Adit A.G., Jonathan M. M. (2006). Association Between Serum 25-Hydroxyvitamin D Level and Upper Respiratory Tract Infection in the Third National Health and Nutrition Examination Survey. Arch Intern Med. 2009 Feb 23; 169(4): 384–390.
9) Mitsuyoshi U., Takaaki S. (2010). Randomized trial of vitamin D supplementation to prevent seasonal influenza A in schoolchildren. Am J Clin Nutr . 2010 May;91(5):1255-60.
10) FemkeB, Tatiana T. (2010). Vitamin D: modulator of the immune system. Immunology. 2011 Oct;134(2):123-39. doi: 10.1111/j.1365-2567.2011.03482.x.
11) Michelino DR, Michele M. (2011). Vitamin D3: a helpful immuno-modulator. Immunology. 2011 Oct;134(2):123-39. doi: 10.1111/j.1365-2567.2011.03482.x.
12) Adrian RM. (2016). Vitamin D supplementation to prevent acute respiratory tract infections: systematic review and meta-analysis of individual participant data. BMJ 2017; 356 doi: https://doi.org/10.1136/bmj.i6583
13) Madhusmita M, Danièle P. (2008). Vitamin D deficiency in children and its management: review of current knowledge and recommendations. Pediatrics . 2008 Aug;122(2):398-417.
Background on Omega-3 (EPA&DHA)
Omega-3 is a class of polyunsaturated fatty acids (PUFAs), which contains three major categories: alpha-linolenic acid (ALA), eicosapentaenoic acid (EPA), and docosahexaenoic acid (DHA). Our following focus will lie on EPA and DHA.
Natural sources of Omega-3
Omega-3 is abundantly present in flaxseed, microalgae and fish. Therefore, fish oil extracts have been a popular product for omega-3 supplements. Although fish oils are the main sources for omega-3 dietary products, they’re not actually produced by fish. Instead, microalgae are the hero behind the scenes. After consuming the phytoplankton which eat microalgae as main food sources, the omega-3 accumulates inside fish bodies.
Recommended EPA + DHA (mg/day):
USA : 270 mg/day (Institute of Medicine)
UK: 200 mg/day (Department of Health)
Belgium: 680 mg/day(Belgian Health Council)
Why should we take Omega-3 Supplements?
Omega-3 has been widely believed to improve cardiovascular health, and many studies have shown consistent results for its effectiveness. Unlike many other supplements, omega-3 has copious research investigating its physiologic effects, especially on cardiovascular disease reduction.
Cardiovascular disease is the leading cause of death in the US, so dietary omega-3 may be an appropriate way to improve overall health outcome. According to a survey conducted around 2012, 7.8 % adults in the U.S. take omega-3 supplements, while only 1.1% children are using the supplement. (3,4)
Aside from the benefits to the cardiovascular system, omega-3 is also crucial for human beings as components. It can not only comprise vital structures like cell membrane (5), but also contribute to the formation of eicosanoids. Hence, their deficiency may end up compromising various body systems, such as cardiovascular and immune systems. (6)
How is omega-3 absorbed in your body?
Since omega-3 is by definition a kind of fatty acid, its absorption is similar to other lipids. After passing through the stomach, omega-3 will be subsequently absorbed by the gastrointestinal tract and be transported to the liver in chylomicron particles. Liver will release these fatty acids in lipoprotein particles into circulation.
Is omega-3 safe? Will it interact with other drugs?
Can omega-3 be harmful?
One of the reasons that omega-3 can reduce cardiovascular risks is the blood-thinning effects, and like other anticoagulants. Bleeding risk could be the inevitable side effect. However, a study argues that high doses of omega-3 (8 to 10 g loading dose over two to five days preoperatively, followed by 2 g/day postoperatively) do not necessarily lead to increased bleeding risks. (7)
Carcinogenicity is usually a concern when it comes to animal products. Current studies support that fish consumption won’t increase cancer risk of any type. (8) However, a little research suggests that higher levels of omega-3 can increase the risk of prostate cancer (9,10), though the meta-analysis finds no solid association between omega-3 and prostate cancer. (11)
Does omega-3 interact with medications or other dietary supplements?
Yes. omega-3 supplements can interact or interfere with some medicines. (12,13)
Increase bleeding risk: Aspirin, Warfarin
Why do we need omega-3?
Cardiovascular risk reduction and microbiome regulation. The most common understanding of omega-3 is its effect on cardiovascular risk. Numerous studies have investigated the clinical effect of omega-3, which mainly focus on EPA and DHA, and many studies show a consistent positive effect on cardiovascular protection, even for those who don’t receive regular medication. For instance, Omega-3 may benefit drug-naïve patients with type 2 diabetes for cardiovascular risk. (14) Due to the abundant supportive research, FDA even approved a health claim stating that omega-3 may help reduce coronary heart disease risk. (15)
In addition to the cardiovascular effect, recent studies show that omega-3 may also play a role in immunity, and it may help regulate the microbiome composition in the gut. (16) Also, the application of omega-3 is not limited to oral supplement, a study shows that enteral delivery of omega-3 improved bacterial diversity and lowered abundance of pathogenic bacteria such as Streptococcus and E.coli on premature infants. (17)
Hello Health® Mighty Might™ Includes Omega-3
Mighty Might™ supports the immune system and helps soothe environmental stressors.
- About Supporting Immune System
Gut microbiota is a very popular topic in immunity. Recent studies show that composition and diversity of gut bacteria are strongly related to the immune system. It turns out that omega-3 may have the potential to regulate gut microbiota. For example, omega-3 PUFAs can lower both Bacteroidetes and Firmicutes, whose ratio has been linked to weight gain and other metabolic conditions, such as insulin resistance. (18)
- About Helping Soothe Environmental Stressors
Air pollution is one of the major environmental stressors, and those who live in cities or near factories. Research found out the protective effect of omega-3 supplement against PM 2.5 long ago, (19) and recent studies show a consistent result that it can help decrease particle-induced pulmonary and systemic inflammation. (20) Therefore, omega-3 may be an ideal supplement for those who are bothered by air pollutants, especially people with asthma or COPD.
1) Harris WS. Omega-3 fatty acids. In: Coates PM, Betz JM, Blackman MR, et al., eds. Encyclopedia of Dietary Supplements. 2nd ed. London and New York: Informa Healthcare; 2010:577-86.
2) D. Ian Givens. (2008). Current intakes of EPA and DHA in European populations andthe potential of animal-derived foods to increase them. Proceedings of the Nutrition Society (2008), 67, 273–280
3) Clarke TC, Black LI. (2015). Trends in the use of complementary health approaches among adults: United States, 2002-2012. Natl Health Stat Report 2015:1-16.
4) Black LI, Clarke TC. (2014). Use of complementary health approaches among children aged 4-17 years in the United States: National Health Interview Survey, 2007-2012. Natl Health Stat Report 2015:1-19.
5) Institute of Medicine, Food and Nutrition Board. Dietary reference intakes for energy, carbohydrate, fiber, fat, fatty acids, cholesterol, protein, and amino acids (macronutrients). Washington, DC: National Academy Press; 2005.
6) Jones PJH, Papamandjaris AA. (2012). Lipids: cellular metabolism. In: Erdman JW, Macdonald IA, Zeisel SH, eds. Present Knowledge in Nutrition. 10th ed. Washington, DC: Wiley-Blackwell; 2012:132-48.
7) Akintoye E, Sethi P. (2019). Fish Oil and Peri-operative Bleeding: Insights from the Omega-3 Fatty Acids for Prevention of Postoperative Atrial Fibrillation (OPERA) Randomized Trial. Circ Cardiovasc Qual Outcomes. 2018 Nov; 11(11): e004584.
8) Aleix SV 1, Philip CC. (2011). Update on the relationship of fish intake with prostate, breast, and colorectal cancers. Crit Rev Food Sci Nutr . Oct-Nov 2011;51(9):855-71.
9) Theodore MB, Cathee T. (2013). Serum phospholipid fatty acids and prostate cancer risk: results from the prostate cancer prevention trial. Am J Epidemiol
. 2011 Jun 15;173(12):1429-39.
10) Song YP, Lynne RW. (2009). Circulating fatty acids and prostate cancer risk in a nested case-control study: the Multiethnic Cohort. Cancer Causes Control. 2009 Mar;20(2):211-23. doi: 10.1007/s10552-008-9236-4. Epub 2008 Sep 27
11) Dominik DA, Julie KB. (2015). Meta-Analysis of Long-Chain Omega-3 Polyunsaturated Fatty Acids (LCω-3PUFA) and Prostate Cancer 12). Nutr Cancer. 2015;67(4):543-54. doi: 10.1080/01635581.2015.1015745.
12) Omega-3 (omega-3 polyunsaturated fatty acids) Interactions. Drugs.com
13) Eicosatetraenoic Acid/ Docosahexaenoic Acid. Drug Interactions. IBM Micromedex.
14) Mariona B, Silvia C. (2016). Effects of sardine-enriched diet on metabolic control, inflammation and gut microbiota in drug-naïve patients with type 2 diabetes: a pilot randomized trial
15) U.S. Food and Drug Administration. (2014). Summary of qualified health claims subject to enforcement discretion. External link disclaimer
16) Cristina M, Jonas Z (2017). Omega-3 fatty acids correlate with gut microbiome diversity and production of N-carbamylglutamate in middle aged and elderly women.Sci Rep 7, 11079. https://doi.org/10.1038/s41598-017-10382-2
17) Noelle Y. Qing Y. (2017). Enteral High Fat-Polyunsaturated Fatty Acid Blend Alters the Pathogen Composition of the Intestinal Microbiome in Premature Infants with an Enterostomy.
18) Lara C, Romina M. (2017). Impact of Omega-3 Fatty Acids on the Gut Microbiota. Int J Mol Sci . 2017 Dec 7;18(12):2645.
19) Isabelle R, Raquel GE. (2008). The effect of supplementation with omega-3 polyunsaturated fatty acids on markers of oxidative stress in elderly exposed to PM(2.5). Environ Health Perspect . 2008 Sep;116(9):1237-42. doi: 10.1289/ehp.10578.
20) Xiang YL. Lei H. (2017) Protection against fine particle-induced pulmonary and systemic inflammation by omega-3 polyunsaturated fatty acids. Biochimica et Biophysica Acta (BBA) - General Subjects. https://doi.org/10.1016/j.bbagen.2016.12.018
Background on Zinc
Zinc is one of the essential trace elements, and a member of one of the major micronutrient subgroups in human nutrition and health (1). Zinc is active in a variety of cellular functions, including signal transduction, transcription and replication (Vallee & Falchuk, 1993) and strongly influences the immune system affecting both nonspecific and acquired immunity (Fraker et al, 2000). Also, it plays a critical role in many biochemical functions, including protein synthesis and nucleic acid metabolism (2)
Furthermore, Zinc is essential in growth and development. Examples of functions that require zinc include mmunity, metabolism, DNA metabolism and repair, reproduction, vision and cognitive (3)
TABLE 1. Various natural sources of Zinc (1)
Oysters, cooked, breaded and fried, 3 ounces
Beef chuck roast, braised, 3 ounces
Crab, Alaska king, cooked, 3 ounces
Beef patty, broiled, 3 ounces
Lobster, cooked, 3 ounces
Pork chop, loin, cooked, 3 ounces
Baked beans, canned, plain or vegetarian, ½ cup
Breakfast cereal, fortified with 25% of the DV for zinc, 1 serving
Chicken, dark meat, cooked, 3 ounces
Pumpkin seeds, dried, 1 ounce
Yogurt, fruit, low fat, 8 ounces
Cashews, dry roasted, 1 ounce
Chickpeas, cooked, ½ cup
Cheese, Swiss, 1 ounce
Oatmeal, instant, plain, prepared with water, 1 packet
Milk, low-fat or non fat, 1 cup
Almonds, dry roasted, 1 ounce
Kidney beans, cooked, ½ cup
Chicken breast, roasted, skin removed, ½ breast
Cheese, cheddar or mozzarella, 1 ounce
Peas, green, frozen, cooked, ½ cup
Flounder or sole, cooked, 3 ounces
Dose Recommendations (1):
- Kids: 5 – 11 mg
- Adults: 11 mg
- Geriatric: 11 mg
- Pregnant women: 11 mg
Why do we need Zinc supplements?
Based on research the following do not consume the daily requirement (3)
- White: Male >70 years, Female > 50 years
- Hispanic: Male >50 years, Female >60 years
- Black: Male >30 years, Female >30 years
Also, figure 1 displays all the possible diseases or morbidities due to zinc deficiency:
Figure 1. Parts which require zinc and the morbidities a deficiency can cause (11)
How is Zinc absorbed in our bodies?
Zinc is absorbed throughout the whole small intestine (4,5) but the major site of intestinal zinc absorption in humans remains controversial. However, using small intestine perfusion techniques in healthy individuals, the major absorption sites in human intestines are found to be both the duodenum and jejunum (6)
Zinc uptake takes place at the intestinal brush border membrane, where it is transported from the lumen into absorptive cells of the epithelium: the enterocytes. The subsequent excretion of the cation at the basolateral side of enterocytes releases it into the portal blood, where it is predominantly bound to albumin, which distributes the metal in the body (7)
Fractional absorption of dietary zinc in humans is typically in the range of 16–50%, which is inversely related to oral zinc intake. Moreover, net absorption is regulated by body zinc homeostasis and, thus, depends on the individual zinc status adapting to prolonged low zinc diets. Consequently, zinc-deficient humans and animals show increased fractional zinc absorption, absorbing up to 92% of dietary zinc (8). Accordingly, human zinc absorption is more efficient from low zinc diets (9) Net absorption is higher from orally administered aqueous zinc solutions than the absorption of the same amount of zinc included in a meal.
Figure 2. Zinc absorption in human body (11)
Hello Health® Mighty Might™ Includes Zinc
Mighty Might™ supports the immune system and helps soothe environmental stressors.
Zinc supplements have been effective as a therapeutic and is important for the following:
- About Immunity
Based on various research studies, zinc supplements: It has been observed that in healthy young adults the oral administration of zinc increases in vitro lymphocyte response to mitogens. Furthermore, oral zinc augments the circulating pool of a T lymphocyte subpopulation in patients with acute lymphoblastic leukaemia 
Zinc supplementation resulted in lower incidence of anorexia and morbidity from cough, diarrhea, fever and vomiting in the stunted children (11)
COVID symptoms and morbidities are: Dry cough, lower RTI, Upper RTI, pneumonia, ventilation associated pneumonia, acute lung injury. Utilizing zinc supplements decreases the probability of the above morbidities and also works as therapeutic. (12)Women who consumed zinc had children with greater birth weight and head circumference (2)
- About Stress
Zinc plays a significant role with respect to the stress response. Proper maintenance of zinc status can help to stabilize serum cortisol levels over time, and zinc intake has been shown to temporarily inhibit cortisol secretions.However, in turn, prolonged stress will deplete zinc concentrations in the blood. (14, 15, 16)
References for Zn:
- NIH: Zinc – fact sheet for health professionals. https://ods.od.nih.gov/factsheets/Zinc-HealthProfessional/
- Goldenberg RL, Tamura T, Neggers Y, et al. The Effect of Zinc Supplementation on Pregnancy Outcome. JAMA. 1995;274(6):463–468. doi:10.1001/jama.1995.03530060037030
- Maret W, Sandstead HH. Zinc requirements and the risks and benefits of zinc supplementation. J Trace Elem Med Biol. 2006;20(1):3-18. doi: 10.1016/j.jtemb.2006.01.006. Epub 2006 Feb 21. PMID: 16632171.
- Sandström, B. (1992). Dose dependence of zinc and manganese absorption in man. Proceedings of the Nutrition Society, 51(2), 211-218. doi:10.1079/PNS19920031
- Maares, Maria, and Hajo Haase. “A Guide to Human Zinc Absorption: General Overview and Recent Advances of In Vitro Intestinal Models.” Nutrients vol. 12,3 762. 13 Mar. 2020, doi:10.3390/nu12030762
- Steinhardt H.J., Adibi S.A. Interaction between transport of zinc and other solutes in human intestine. Am. J. Physiol.1984;247:G176–G182. doi: 10.1152/ajpgi.1984.247.2.G176
- Reyes J.G. Zinc transport in mammalian cells. Am. J. Physiol.1996;270:C401–C410. doi: 10.1152/ajpcell.1996.270.2.C401.
- Istfan N.W., Janghorbani M., Young V.R. Absorption of stable70 zn in healthy young men in relation to zinc intake. Am. J. Clin. Nutr.1983;38:187–194. doi: 10.1093/ajcn/38.2.187.
- Hunt J.R., Beiseigel J.M., Johnson L.K. Adaptation in human zinc absorption as influenced by dietary zinc and bioavailability. Am. J. Clin. Nutr.2008;87:1336–1345. doi: 10.1093/ajcn/87.5.1336.
- Maares, Maria, and Hajo Haase. “A Guide to Human Zinc Absorption: General Overview and Recent Advances of In Vitro Intestinal Models.” Nutrients vol. 12,3 762. 13 Mar. 2020, doi:10.3390/nu12030762
- Zinc supplementation and stunted infants in Ethiopia: a randomised controlled trial Melaku Umeta, Clive E West, Jemal Haidar, Paul Deurenberg, Joseph G A J Hautvast
- The Potential Impact of Zinc Supplementation on COVID-19 Pathogenesis Inga Wessels 1†, Benjamin Rolles 2† and Lothar Rink 1
- Zinc supplementation decreases incidence of infections in the elderly: effect of zinc on generation of cytokines and oxidative stress1–3 Ananda S Prasad, Frances WJ Beck, Bin Bao, James T Fitzgerald, Diane C Snell, Joel D Steinberg, and Lavoisier J Cardozo
- Faure H, Peyrin JC, Richard MJ, Favier A. Parenteral supplementation with zinc in surgical patients corrects postoperative serum-zinc drop. Biol Trace Elem Res. 1991;30(1):37-45.
- Brandão-Neto J, de Mendonça BB, Shuhama T, Marchini JS, Pimenta WP, Tornero MT. Zinc acutely and temporarily inhibits adrenal cortisol secretion in humans. A preliminary report. Biol Trace Elem Res. 1990;24(1):83-9.
- Córdova A, Navas FJ. Effect of training on zinc metabolism: changes in serum and sweat zinc concentrations in sportsmen. Ann Nutr Metab. 1998;42(5):274-82.
Background on Pre- and Probiotics
Probiotics are microorganisms that have health benefits when consumed. Although people often think of bacteria and other microorganisms as harmful, in fact, many are helpful. Some bacteria are known to help digest food, destroy cells that induce disease, or they may produce vitamins. Many of the microorganisms in probiotic products are the same as or similar to microorganisms that naturally occur/live in our bodies. (1)
Prebiotics are described as “selectively fermented ingredients that result in specific changes in the composition and/or activity of the gastrointestinal microbiota, thus conferring benefit(s) upon host health”. (2)Prebiotics feed probiotics and provide optimum environments for “good” bacteria to grow. Commercial products containing both prebiotic sugars and probiotic organisms are often called “synbiotics.”
Natural sources of Pre and Probiotics
Probiotics are found in yogurt, kefir, cottage cheese, cheddar cheese, sauerkraut, kombucha, pickled vegetables, kimchi, miso, and tempeh, and probiotics are found in onions, garlic, leeks, soybeans, chicory root, honey, banana, and Jerusalem artichoke. (3)
Why should we take Pre and Probiotic Supplements?
Probiotics and prebiotics can help restore the balance when our gut becomes unbalanced with unhealthy levels of certain bacteria, according to Harvard Health. They've been shown to secrete protective substances, which may turn on the immune system and prevent pathogens from taking hold and creating major disease. Probiotics taken as a supplement may also reduce the number of colds you'll have in a year. Probiotics are commonly used to reduce gastrointestinal symptoms that are not due to acute illness, such as gas, bloating, and constipation. (1)
Figure 1: Diseases influenced by gut microbial metabolism. The variety of systemic diseases that are directly influenced by gut microbial metabolism and its influence on other pathways like the innate immune system. (9)
How do probiotics manifest in our gut?
According to a study by Zmora et al, the human gastrointestinal tract is colonized by microorganisms, including bacteria, viruses, and fungi. The activity and composition of these microorganisms may affect human health and disease. Probiotics may influence the intestinal microbiota and can transiently colonize the human gut mucosa in highly individualized patterns, depending on the baseline microbiota, probiotic strain, and gastrointestinal tract region (4).
According to an article by Hill et al, probiotics exert health effects via nonspecific, species-specific, and strain-specific mechanisms. The nonspecific mechanisms depend on the strain, species, or even type of commonly used probiotic supplements and include inhibition of the growth of pathogenic microorganisms in the gastrointestinal tract, production of bioactive metabolites like short-chain fatty acids, and reduction of luminal pH in the colon. Species-specificmechanisms include vitamin synthesis, gut barrier reinforcement, and toxin neutralization. Strain-specific mechanisms, which are rare and are used by only a few strains, include cytokine production, immunomodulation, and effects on the endocrine (hormone) and nervous systems. (5)
Are prebiotics and probiotics safe? Will they interact with other drugs?
Can prebiotics and probiotics be harmful?
Probiotics have an extensive history of safe use, particularly in healthy people. However, few studies have looked at the safety of probiotics in detail, so there is no consensus on the frequency and severity of side effects. The risk of harmful effects from probiotics is greater in people with severe illnesses or compromised immune systems. Possible harmful effects of probiotics include infections, production of harmful substances by the probiotic microorganisms, and transfer of antibiotic resistance genes to other microorganisms in the digestive tract. (1)Some probiotic products have been reported to contain microorganisms other than those listed on the label. So, it is important to ensure transparent labelling practices among supplement manufacturers.
However, prebiotics are assumed to lack life-threatening or severe side effects. Intestinal enzymes cannot break down oligosaccharides and polysaccharides. They are transported to the colon to be fermented by the gut microbiota. Therefore, the side effects of prebiotics are mostly the result of their osmotic functions. In this regard, osmotic diarrhea, bloating, cramping, and flatulence could be experienced in prebiotic recipients. A study by Svensson et al showed that low (2.5–10 g/day) and high (40–50 g/day) doses of prebiotics can cause flatulence and diarrhea noting that, a daily dose of 2.5–10 g prebiotics is required to exert their beneficial effect on human health. This means that prebiotics within their therapeutic doses can cause mild to moderate side effects. (6)
Do Probiotics and Prebiotics interact with medications or other dietary supplements?
Drugs are known to interfere with administered probiotics. Interactions between probiotics and warfarin are known. There is also potential interaction with warfarin; for example, Bifolac is a probiotic that is used for normalisation of gut flora, prophylactic, or temporary gastrointestinal disorders. The drug contains two bacterial strains: Lactobacillus rhamnosusand Bifidobacterium longum. (7,8)
Hello Health® Belly Great™ Includes Prebiotics & Probiotics
Supports the immune system and helps maintain healthy digestion and bones.
Probiotic and prebiotic supplements may be important for the following:
- About Immunity:
There is a dynamic relationship between the immune system and the microbiota. The intestinal mucosa averts threats by signaling to the innate immune system through toll-like receptors that recognize and bind to specific microbial macromolecules, like lipopolysaccharide, flagellin, peptidoglycan, and N-formylated peptides. In the intestinal mucosa, the activation of toll-like receptors initiates nuclear factor-kB pathways, mitogen-activated protein kinase, and caspase-dependent signaling cascades.The result can be a protective response to commensal bacteria, an inflammatory response to pathogenic organisms, or a trigger of apoptosis. Therefore, commensal bacteria of the gastrointestinal tract play active roles in the development and balance of the immune system. (10)
- About Digestive Health
In the case of irritable bowel syndrome, proinflammatory bacterial species, including Enterobacteriaceae, are present at high levels in patients with IBS, who typically also have a reduction in amounts of Lactobacillus and Bifidobacterium. (11)A meta-analysis of 23 random controlled trials in a total of 2,575 patients found that probiotics reduced the risk that IBS symptoms would persist or not improve by 21% (12). A second meta-analysis of 15 randomized- controlled trials in a total of 1,793 patients with IBS found that probiotics reduced overall symptoms and abdominal pain after 8 to 10 weeks of therapy, compared to the control/placebo cases. In children, these supplements also were found to improve mucosal barrier function. (13) Overall, the evidence indicates that probiotics might reduce some symptoms of digestive issues like IBS. However additional, more thorough clinical trials are needed to confirm the effect of a specific strain, dose, and duration of treatment in addition to the specific type of digestive issue.
References for Prebiotics and Probiotics:
(2) Gibson G.R., Scott K.P., Rastall R.A., Tuohy K.M., Hotchkiss A., Dubert-Ferrandon A., Gareau M., Murphy E.F., Saulnier D., Loh G., et al. Dietary prebiotics: Current status and new definition. Food Sci. Technol. Bull. Funct. Foods.2010;7:1–19. doi: 10.1616/1476-2137.15880.
(4) Zmora N, Zilberman-Schapira G, Suez J, Mor U, Dori-Bachash M, Bashiardes S, et al. Personalized Gut Mucosal Colonization Resistance to Empiric Probiotics Is Associated with Unique Host and Microbiome Features. Cell 2018;174:1388-405.e21
(5) Hill C, Guarner F, Reid G, Gibson GR, Merenstein DJ, Pot B, et al. The International Scientific Association for Probiotics and Prebiotics consensus statement on the scope and appropriate use of the term probiotic. Nat Rev Gastroenterol Hepatol 2014;11:506-14
(6) Svensson U., Håkansson J. Safety of Food and Beverages: Safety of Probiotics and Prebiotics. Elsevier; New York, NY, USA: 2014.
(7) Williams NT, Am J Health Syst Pharm. 2010 Mar 15; 67(6):449-58.
(8) [Possible interaction between probiotics and warfarin]. Lindh J, Lakartidningen. 2010 Mar 31-Apr 13; 107(13-14):917.
(9) Kinross et al. Genome Medicine 2011 3:14.
(10) Vyas, Usha, and Natarajan Ranganathan. “Probiotics, prebiotics, and synbiotics: gut and beyond.” Gastroenterology research and practice vol. 2012 (2012): 872716. doi:10.1155/2012/872716
(11) Zhuang X, Xiong L, Li L, Li M, Chen M. Alterations of gut microbiota in patients with irritable bowel syndrome: A systematic review and meta-analysis. J Gastroenterol Hepatol 2017;32:28-38
(12) Ford AC, Quigley EM, Lacy BE, Lembo AJ, Saito YA, Schiller LR, et al. Efficacy of prebiotics, probiotics, and synbiotics in irritable bowel syndrome and chronic idiopathic constipation: systematic review and meta-analysis. Am J Gastroenterol 2014;109:1547-61; quiz 6, 62.
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Several years of scientific and clinical research clearly show that a deficiency or an imbalance in any of the components included in this review have an impact on the overall health. Under conditions where food cannot be consumed to provide these nutrients, it is important to obtain them by supplementation under the right amounts. The same is true when a particular disease compromises the metabolism of any of the mentioned nutrients. The nervous system, Immune system and gut microbiota are the only mentioned and reviewed compartments here. Nevertheless, the vitamins and minerals that are part of this review have shown to impact key cellular processes, opening the possibility that many other compartments of our body can be benefited by the correct supplementation under systemic deficiencies. Even though many of the molecular mechanisms by how these components work is very well understood, many others are still under research. For example, there is an increasing knowledge about how our microbiota impacts other systems of our body, and how metabolites could shape the composition of the microbiota in humans. The manipulation of these pathways provides an attractive strategy for maximizing the contribution of vitamins and micronutrients to health. Ensuring a correct supplementation that contributes to achieve normal and physiologic amounts is the first and key step we have to make.