Ingredient #1: Total Carbohydrate

Provide stored energy

• The Role of Skeletal Muscle Glycogen Breakdown for Regulation of Insulin Sensitivity by Exercise
• https://www.frontiersin.org/journals/physiology/articles/10.3389/fphys.2011.00112/full
• Glycogen is the storage form of carbohydrates in mammals. In humans the majority of glycogen is stored in skeletal muscles (∼500 g) and the liver (∼100 g)
• During a hyperinsulinemic euglycemic clamp, 70–90% of glucose disposal will be stored as muscle glycogen in healthy subjects.
• The glycogen stores in skeletal muscles are limited because an efficient feedback-mediated inhibition of glycogen synthase prevents accumulation. De novo lipid synthesis can contribute to glucose disposal when glycogen stores are filled. Exercise physiologists normally consider glycogen’s main function as energy substrate.
• Glycogen is the main energy substrate during exercise intensity above 70% of maximal oxygen uptake (Vo2max⁡) and fatigue develops when the glycogen stores are depleted in the active muscles. After exercise, the rate of glycogen synthesis is increased to replete glycogen stores, and blood glucose is the substrate. Indeed insulin-stimulated glucose uptake and glycogen synthesis is elevated after exercise, which, from an evolutional point of view, will favor glycogen repletion and preparation for new “fight or flight” events.
• In the modern society, the reduced glycogen stores in skeletal muscles after exercise allows carbohydrates to be stored as muscle glycogen and prevents that glucose is channeled to de novo lipid synthesis, which over time will causes ectopic fat accumulation and insulin resistance.
• The reduction of skeletal muscle glycogen after exercise allows a healthy storage of carbohydrates after meals and prevents development of type 2 diabetes.

Helps preserve muscle

• The Effect of Carbohydrates on Ammonium and Ketoacid Excretion during Starvation
• https://www.ncbi.nlm.nih.gov/pmc/articles/PMC292366/pdf/jcinvest00204-0169.pdf
• In this study a systematic investigation was undertaken to define the minimal amount of exogenous carbohydrate required to reduce urinary ketoacid and ammonium excretion during starvation.
• the effect of the ingested carbohydrate on acid-base parameters, blood glucose, serum insulin, plasma free fatty acids, and blood acetoacetate and beta-hydroxybutyrate concentrations was evaluated.
• The results of the study indicate that minute amounts of carbohydrate (7.5 g ingested daily) will significantly alter the excretion of urinary ketoacids and ammonium in man after prolonged starvation.

Ingredient #2: Vitamin A

Supports a Healthy Immune System

• Increased risk of respiratory disease and diarrhea in children with preexisting mild vitamin A deficiency
• https://www.sciencedirect.com/science/article/abs/pii/S0002916523245098?via%3Dihub
• Preschool-age rural Indonesian children were reexamined every 3 months for 18 months.
• An average of 3135 children were free of respiratory disease and or diarrhea at the examination initiating each of the six, 3-month follow-up intervals
• Children with mild xerophthalmia (night blindness and/or Bitot's spots) at the start and end of an interval developed respiratory disease and diarrhea at twice (p < 0.001) and three times (p < 0.001) the rate, respectively, of children with normal eyes during the same interval, independent of age and anthropometric status (weight for length).
• The risk of respiratory disease and diarrhea were more closely associated with vitamin A status than with general nutritional status. These results may explain much of the excess mortality recently reported for mildly vitamin A-deficient children.

Supports Bone Health

• The Effect of Vitamin A on Fracture Risk: A Meta-Analysis of Cohort Studies
• https://www.mdpi.com/1660-4601/14/9/1043
• A total of 319,077 participants over the age of 20 years were included. Higher dietary intake of retinol and total vitamin A may slightly decrease total fracture risk (RR with 95% CI: 0.95 (0.91, 1.00) and 0.94 (0.88, 0.99), respectively), and increase hip fracture risk (RR with 95% CI: 1.40 (1.02, 1.91) and 1.29 (1.06, 1.57), respectively).
• Lower blood level of retinol may slightly increase total fracture risk (RR with 95% CI: 1.11 (0.94, 1.30)) and hip fracture risk (RR with 95% CI: 1.27 (1.05, 1.53)).
• In addition, higher β-carotene intake was weakly associated with the increased risk of total fracture (RR with 95% CI: 1.07 (0.97, 1.17)).
• Our data suggest that vitamin A intake and level may differentially influence the risks of total and hip fractures. Clinical trials are warranted to confirm these results and assess the clinical applicability.

Ingredient #3: Vitamin C

Supports Iron Absorption

• Ascorbic acid uptake affects ferritin, Dcytb and Nramp2 expression in Caco-2 cells
• https://link.springer.com/article/10.1007/s00394-008-0741-8
• Ascorbic acid (vitamin C) enhances iron uptake in human intestinal cells
• Cell lysates were collected and subjected to SDS-PAGE and Western blotting. The blotted samples were stained with specific antibodies (Rabbit alpha-human-Nramp2 and Goat alpha-human Dcytb) against the respective proteins and the bands achieved were analysed by reflective density measurements
• The results indicate that ascorbic acid uptake induces both iron independent and iron dependent ferritin formation, but the effect on iron dependent ferritin expression was significantly greater (470% compared to 19%).
• The influence of intracellular ascorbic acid status on ferritin formation must be considered in iron uptake studies in Caco-2 cells

Helps prevent iron deficiency

• Prediction of dietary iron absorption: an algorithm for calculating absorption and bioavailability of dietary iron
• https://www.sciencedirect.com/science/article/pii/S0002916523135532?via%3Dihub
• The basis for the algorithm was the absorption of iron from a wheat roll (22.1 ± 0.18%) containing no known inhibitors or enhancers of iron absorption and adjusted to a reference dose absorption of 40%. This basal absorption was multiplied by the expected effect of different amounts of dietary factors known to influence iron absorption
• Good agreement was seen when measurements of iron absorption from 24 complete meals were compared with results from use of the algorithm (r2 = 0.987) and when mean iron absorption in 31 subjects served a varied whole diet labeled with heme- and nonheme-iron tracers over a period of 5 d was compared with the mean total iron absorption calculated by using the algorithm (P = 0.958).

Effect of vitamin C supplementations on iron deficiency anemia in Chinese children

• https://pubmed.ncbi.nlm.nih.gov/1642785/
• A total of 65 children with mild iron deficiency anemia (IDA) were divided into 5 groups, and received 0, 25, 50, 100 and 150 mg/day of vitamin C (VC) respectively every day for 8 weeks.
• At a daily average intake of about 30 mg of VC and 7.5 mg of Fe, the results of the study indicate that: (1) VC supplement alone could effectively control children's IDA, and a dose-dependent relationship was observed. (2) 50 mg/day of VC is the most efficient dosage and 6 weeks is the shortest time for an effective therapy. (3) With a diet predominantly comprised of plant foods, it is suggested that appropriate dose of VC should be supplemented for the children during winter and spring in northeastern areas of China.

Ingredient #4: Vitamin D

Vitamin D regulates mood and reduces depression

• The effect of vitamin D supplement on negative emotions
• https://onlinelibrary.wiley.com/doi/10.1002/da.23025
• The analysis covered 25 trials with a total of 7,534 participants and revealed an effect of vitamin D on negative emotion (Hedges' g = −0.4990, 95% CI [−0.8453, −0.1528], p = .0047, I2 = 97.7%).
• Subgroup analysis showed that vitamin D had an effect on patients with major depressive disorder and on subjects with serum 25(OH)D levels ≤50 nmol/L.
• The pooled data from trials of vitamin D supplementation lasting ≥8 weeks and dosage ≤4,000 IU/day indicated that vitamin D had an effect.
• Our results support the hypothesis that vitamin D supplementation can reduce negative emotions.

Supporting immune health

• Vitamin D’s Effect on Immune Function
• https://www.mdpi.com/2072-6643/12/5/1248
• The attention is shifted towards the importance of the extra-skeletal effects of vitamin D, with special emphasis on the immune system.
• The first hint of the significant role of vitamin D on the immune system was made by the discovery of the presence of the vitamin D receptor on almost all cells of the immune system.
• The evidence of a link between vitamin D deficiency and adverse outcomes is overwhelming and clearly points towards avoidance of vitamin D deficiency especially in early life.

Ingredient #5: Vitamin E

• https://ods.od.nih.gov/factsheets/VitaminE-HealthProfessional/#en6
• Vitamin E is involved in immune function and, as shown primarily by in vitro studies of cells, cell signaling, regulation of gene expression, and other metabolic processed. Alpha-tocopherol inhibits the activity of protein kinase C, an enzyme involved in cell proliferation and differentiation in smooth muscle cells, platelets, and monocytes .
• Vitamin-E-replete endothelial cells lining the interior surface of blood vessels are better able to resist blood cell components adhering to this surface.
• Vitamin E also increases the expression of two enzymes that suppress arachidonic acid metabolism, thereby increasing the release of prostacyclin from the endothelium, which, in turn, dilates blood vessels and inhibits platelet aggregation

Vitamin E intake critical during 'the first 1,000 days'

• https://www.sciencedaily.com/releases/2014/09/140915083901.htm
• Inadequate vitamin E is associated with increased infection, anemia, stunting of growth and poor outcomes during pregnancy for both the infant and mother.
• Overt deficiency, especially in children, can cause neurological disorders, muscle deterioration, and even cardiomyopathy.
• Studies with experimental animals indicate that vitamin E is critically important to the early development of the nervous system in embryos, in part because it protects the function of omega-3 fatty acids, especially DHA, which is important for brain health. The most sensitive organs include the head, eye and brain.
• One study showed that higher vitamin E concentrations at birth were associated with improved cognitive function in two-year-old children.

What Should Parents Know About Vitamin E?

• https://health.usnews.com/health-news/blogs/eat-run/articles/what-should-parents-know-about-vitamin-e
• Vitamin E has important roles in your child’s body. Vitamin E is an antioxidant, which means it helps counter the effects of free radicals in the body. Free radicals are chemicals formed in our body during various normal chemical reactions in the body, and they can cause damage to cells
• Vitamin E also has a role in immune system function and clot prevention

Ingredient #6: Thaimin

The Importance of Vitamin B1, or Thiamin, in Your Child's Diet

https://health.usnews.com/health-news/blogs/eat-run/articles/the-importance-of-vitamin-b1-or-thiamin-in-your-childs-diet

Vitamin B1 has an important role in energy metabolism and helps activate enzymes involved in energy metabolism. Therefore, it's necessary for cells to function properly and for promoting optimal growth and development.

It plays a critical role in generating ATP, the basic energy molecule in the body. It's also involved in the metabolism of certain amino acids like leucine, isoleucine and valine, as well indirectly in fat metabolism.

Dietary Vitamin B Complex: Orchestration in Human Nutrition throughout Life with Sex Differences

• https://www.mdpi.com/2072-6643/14/19/3940
• The importance of B complex vitamins starts early in the human life cycle and continues across its different stages. At the same time, numerous reports have emphasized the critical role of adequate B complex intake
• Thiamine, riboflavin, niacin, pyridoxine, and folic acid are crucial for maternal and fetal health. During infancy and childhood, B vitamins are integrated with physical and psychological development that have a pivotal impact on one's overall health in adolescence and adulthood

The importance of thiamine (vitamin B1) in humans

• https://portlandpress.com/bioscirep/article/43/10/BSR20230374/233247/The-importance-of-thiamine-vitamin-B1-in-humans
• Thiamine is absorbed to the greatest extent by the intestinal walls, where T+ it is transferred to the blood, where its target places are erythrocytes, plasma, leukocytes and platelets
• Subsequently, thiamine is taken up by cells within various tissues including the liver and heart from the blood; however, in the case of neuronal tissue, thiamine is transported from the blood into the cerebrospinal fluid via the blood–brain barrier (BBB). Once within the cell, further transport occurs through mitochondrial and nuclear membranes.
• The total amount of vitamin B1 in the body is 30 mg, 40% of which is in the muscles. The phosphorylated form of thiamine gets stored in the brain, heart, liver and kidneys. As thiamine has a short half-life of only one to 12 h, it is important to consume it regularly in the diet. If not, thiamine storage is depleted within 2–3 weeks
• Thiamine has been shown to inhibit the activity of acetylcholine esterase (AChE): an enzyme that breaks down one of the most important neurotransmitters, acetylcholine, into choline and acetic acid. Supplementation with thiamine increases AChE activity. Therefore, thiamine is an important in enzymatic processes involved in brain development, brain function, maintenance, and interneuronal communication
• Vitamin B1 facilitates the uptake of GABA (γ-butyric acid) neurotransmitter, and its deficiency results in cell damage, affecting cerebellum activity. Moreover, thiamine is involved in maintaining the proper structure of the myelin sheaths, and therefore contributes to the speed of nerve conduction.

Ingredient #7: Riboflavin

Supplementation with Riboflavin (Vitamin B2) for Migraine Prophylaxis in Adults and Children: A Review

• https://econtent.hogrefe.com/doi/10.1024/0300-9831/a000225
• Low vitamin B2 can lead to mitochondrial dysfunction and may have an effect on migraine pathogenesis. The aim of the present study was to carry out a review of existing evidence regarding the effects of riboflavin (vitamin B2) supplementation on migraine prophylaxis in adults and children.
• We searched the databases of PubMed, Science Direct, Google Scholar, and Springer between 1990 and December 2013. Key words included vitamin B2, riboflavin, migraine, vomiting headache, and prevention.
• Finally, eleven eligible articles were found: seven involved studies with adults and four involved studies with children. The results indicated that supplementation with vitamin B2 in adults can play a positive role in reducing the frequency and duration of migraine attacks with no serious side effects.

Effectiveness of riboflavin in pediatric migraine prevention

• https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3952759/
• More than 11% of children 5 to 15 years old and 28% of adolescents 15 to 19 years old suffer from migraine, and most of them will seek medical consultation at least once during childhood. The prevalence of migraine increases with age; it is slightly higher in boys before puberty and 1.5 times more frequent in girls in adolescence. Childhood migraine might result in increased school absences, compromised academic performance, and decreased participation in extracurricular activities.
• One retrospective study reported decreased migraine frequency in younger patients and decreased intensity in male patients. Among 41 Italian children (8 to 18 years of age) who received either 200 or 400 mg/d of riboflavin for 3, 4, or 6 months, riboflavin reduced migraine frequency (21.7 [SD 13.7] vs 13.2 [SD 11.8]; P<.01), particularly in children younger than 12 years old, and decreased intensity (2 [SD 0.5] vs 1.6 [SD 0.8]; P<.01) predominantly in boys (P<.05).
• In a 2010 randomized double-blind placebo-controlled trial, 42 children from the Netherlands who were 6 to 13 years old received 50 mg/d of riboflavin for 16 weeks, followed by a 4-week break and 16 weeks of placebo or vice versa
• there was a significant reduction in tension headaches (P<.04) reported by those in the riboflavin group.
• If a provider decides that the child should try riboflavin, the recommended dose should be 50 to 400 mg/d for a minimum of 4 months

Ingredient #8: Niacin

• A Pilot Study of the Effects of Niacin Administration on Free Fatty Acid and Growth Hormone Concentrations in Children with Obesity
• https://onlinelibrary.wiley.com/doi/10.1111/ijpo.12184
• Dose-finding study of nondiabetic children age 6-12y with BMI≥95th percentile given niacin 250mg q2h × 3 doses (n=2), 500mg q2h × 3 doses (n=5), or 500mg q1h × 4 doses (n=5).
• 8 boys and 4 girls (age 9.7±1.8y; BMI 26.4±3.1kg/m2; BMIz 2.2±.25) were studied.
• FFA decreased as the dose and frequency of niacin increased (p=.01). Niacin 500mg q1h 4 doses suppressed FFA <0.2 mEq/L and significantly increased GH (p =.04). Adverse effects were flushing/warmth (100%), tingling (60%), and GI complaints (20-40%).
• Niacin 500mg q1h significantly lowered serum FFA and increased GH. These pilot data suggest that high FFA is an important suppressor of GH secretion in children with obesity.

Ingredient #9: Vitamin B6

High‐dose Vitamin B6 supplementation reduces anxiety and strengthens visual surround suppression

• https://onlinelibrary.wiley.com/doi/10.1002/hup.2852
• 478 young adults were recruited over five linked phases. Self‐reported anxiety (N = 265) and depression (N = 146) were assessed at baseline and after supplementation
• Vitamin B6 supplementation reduced self‐reported anxiety and induced a trend towards reduced depression, as well as increased surround suppression of visual contrast detection, but did not reliably influence the other outcome measures. Vitamin B12 supplementation produced trends towards changes in anxiety and visual processing.

Vitamin B6 for PMS (premenstrual syndrome)

• https://naturopathicpediatrics.com/2023/01/18/supplementing-vitamin-b6-in-children-and-teens-pms-adhd-autism-and-more/
• Some studies show vitamin B6 supplements to be effective at reducing the symptoms associated with premenstrual syndrome (PMS).
• A recent clinical trial found that 80 mg of pyridoxine taken across three cycles was found to significantly reduce PMS symptoms such as moodiness, forgetfulness, bloating, and anxiety.
• The most significant effect was on reducing anxiety, likely due to the role of vitamin B6 in neurotransmitter synthesis. In adolescents, vitamin B6 may be beneficial in easing symptoms associated with PMS following menarche.

Vitamin B6 and Cognitive function

• https://naturopathicpediatrics.com/2023/01/18/supplementing-vitamin-b6-in-children-and-teens-pms-adhd-autism-and-more/
• Considering the association between vitamin B6, mood, and mental function previously discussed, it’s easy to see how a connection may be drawn to improving overall cognitive function.
• Vitamin B6 also impacts the brain by managing homocysteine levels.
• A deficiency in vitamin B6 can result in elevations of homocysteine, a known risk factor for cerebrovascular disease that may have toxic effects on the neurons of the central nervous system.

Ingredient #10: Folate

Proper Doses & Benefits of Folate for Kids

• https://hiyahealth.com/blogs/news/doses-and-benefits-of-folate-for-kids
• Folate helps the body make new blood cells and helps to keep the heart healthy. This is important for everyone, no matter their age. Children are constantly growing. Babies have about 270 mL of blood in their body, children have about 2,650 mL of blood in their body, and adults usually have over 5,000 mL of blood in their bodies.
• Blood volume increases substantially as your child grows. That’s why folate is crucially important at every stage of life. The body needs folate to keep up with the growing demand for new blood cells, and once the body is done growing, it needs folate to maintain the proper amount of blood cells.
• The body needs less than 1 mg of folate each day, so folate is generally measured in micrograms (mcg) or thousandths of a milligram.
• Newborn to 6 months old – 65 mcg folate daily
• Seven months old to 12 months old – 80 mcg folate daily
• One year old to 3 years olds -- 150 mcg folate daily
• Four years old to 8 years old – 200 mcg folate daily
• Nine years old to 13 years old – 300 mcg folate daily
• Over 13 years old, non-pregnant, non-breastfeeding people -- 400 mcg folate daily

Ingredient #11: Vitamin B12

Oral vitamin B12 treatment is effective for children with nutritional vitamin B12 deficiency

• https://onlinelibrary.wiley.com/doi/10.1111/jpc.12652
• Forty-seven children (from 1 month to 17 years) with vit-B12 levels below 200 pg/mL were allocated either of two study groups: Group 1 (1-20 months) and Group 2 (6-17 years) which were subdivided according to the duration of treatment (Group 1A&2A: 4 months; Group 1B&2B: 8 months of 1000 μg oral vit-B12, every day for a week, every other day for 2 weeks, 2 days a week for 2 weeks, then once a week).
• Vit-B12 levels among all groups were significantly restored following high oral vit-B12 doses (P = 0.013, P = 0.001), the regimen being more effective in Group1A and Group1B.
• Data from this study indicate that oral vit-B12 (1000 μg) for 4 months is effective, giving clinicians more choice, for treatment of children with nutritional vit-B12 deficiency

Correlation between Vitamin B12 and Mental Health in Children and Adolescents: A Systematic Review and Meta-analysis

• https://www.cpn.or.kr/journal/view.html?doi=10.9758/cpn.22.1040
• To conduct the association between vitamin B12 and mental health in children and adolescents. Five databases were searched for observational studies in any language reporting on mental health and vitamin B12 levels or intake in children and adolescents from inception to March 18, 2022
• Fifty six studies containing 37,932 participants were identified in the review. Vitamin B12 levels were lower in participants with autism spectrum disorders (ASD) (standardized mean difference [SMD], -1.61; 95% confidence interval [95% CI], -2.44 to -0.79; p ＜ 0.001), attention deficit hyperactivity disorders (SMD, -0.39; 95% CI, -0.78 to -0.00; p = 0.049) compared with control group. Vitamin B12 intake were lower in participants with ASDs (SMD, -0.86; 95% CI, -1.48 to -0.24; p = 0.006) compared with control group,
• Higher vitamin B12 intake were associated with lower risk of depression (odds ratio [OR], 0.79; 95% CI, 0.63-0.98; p = 0.034) and behavioral problems (OR, 0.83; 95% CI, 0.69-0.99; p = 0.04). The vast majority of included studies supported potential positive influence of vitamin B12 on mental health, and vitamin B12 deficiency may be a reversible cause for some mental health disorders in children and adolescents.

Vitamin B12 and Folic Acid Improve Gross Motor and Problem-Solving Skills in Young North Indian Children: A Randomized Placebo-Controlled Trial

• https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0129915
• Children aged six to 30 months, received supplement with placebo or vitamin B12 and/or folic acid for six months. Children were allocated in a 1:1:1:1 ratio in a factorial design and in blocks of 16. We measured development in 422 children by the Ages and Stages Questionnaire 3rd ed. at the end of the intervention.
• Compared to placebo, children who received both vitamin B12 and folic acid had 0.45 (95% CI 0.19, 0.73) and 0.28 (95% CI 0.02, 0.54) higher SD-units in the domains of gross motor and problem solving functioning, respectively.
• The effect was highest in susceptible subgroups consisting of stunted children, those with high plasma homocysteine (> 10 μmol/L) or in those who were younger than 24 at end study
• Our findings suggest that supplementation of vitamin B12 and folic acid benefit development in North Indian Children.

Cobalamin and folate status predicts mental development scores in North Indian children 12-18 mo of age

• https://www.sciencedirect.com/science/article/pii/S0002916523054102?via%3Dihub
• The objective was to measure the association of plasma concentrations of folate, cobalamin, total homocysteine, and methylmalonic acid with cognitive performance at 2 occasions, 4 mo apart, in North Indian children aged 12-18 mo.
• Each 2-fold increment in plasma cobalamin concentration was associated with a significant increment in the mental development index score of 1.3 (95% CI: 0.2, 2.4; P = 0.021). Furthermore, each 2-fold increment in homocysteine or methylmalonic acid concentration was associated with a decrement in mental development index score of 2.0 (95% CI: 0.5, 3.4; P = 0.007) or 1.1 (95% CI: 0.3, 1.8; P = 0.004) points, respectively. Plasma folate concentration was significantly and independently associated with mental development index scores only when children with poor cobalamin status were excluded, ie, in those who had cobalamin concentrations below the 25th percentile.
• Cobalamin and folate status showed a statistically significant association with cognitive performance

Vitamin B-12 and Cognition in Children

• https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5015033/
• This review was conducted to examine the evidence that links vitamin B-12 and cognition in children. The search strategy resulted in 17 studies: 3 cross-sectional, 1 case–control, and 12 cohort studies, and 1 randomized trial.
• Cognitive processes assessed included attention, memory, and perception. Developmental outcomes, academic performance, and intelligence quotient were also considered.
• Despite the high prevalence of vitamin B-12 insufficiency and associated risk of adverse cognitive outcomes in children, to our knowledge, no studies to date have been conducted to examine the effects of vitamin B-12 supplementation on cognition in children.
• The role of vitamin B-12 in the etiology of child cognitive outcomes needs to be elucidated to inform public health interventions.

Ingredient #12: Biotin

Pharmacological effects of biotin

• https://www.sciencedirect.com/science/article/abs/pii/S0955286305000926?via%3Dihub
• Biotin regulates gene expression and has a wide repertoire of effects on systemic processes. The vitamin regulates genes that are critical in the regulation of intermediary metabolism: Biotin has stimulatory effects on genes whose action favors hypoglycemia (insulin, insulin receptor, pancreatic and hepatic glucokinase); on the contrary, biotin decreases the expression of hepatic phosphoenolpyruvate carboxykinase, a key gluconeogenic enzyme that stimulates glucose production by the liver.
• The findings that biotin regulates the expression of genes that are critical in the regulation of intermediary metabolism are in agreement with several observations that indicate that biotin supply is involved in glucose and lipid homeostasis

Biotin supplementation reduces plasma triacylglycerol and VLDL in type 2 diabetic patients and in nondiabetic subjects with hypertriglyceridemia

• https://www.sciencedirect.com/science/article/abs/pii/S0753332206000539?via%3Dihub
• Several studies have reported a relationship between biotin and blood lipids. In the present work we investigated the effect of biotin administration on the concentration of plasma lipids, as well as glucose and insulin in type 2 diabetic and nondiabetic subjects.
• Eighteen diabetic and 15 nondiabetic subjects aged 30-65 were randomized into two groups and received either 61.4 micromol/day of biotin or placebo for 28 days.
• We found that the vitamin significantly reduced (P=0.005) plasma triacylglycerol and VLDL concentrations. Biotin produced the following changes (mean of absolute differences between 0 and 28 day treatment+/-S.E.M.): a) triacylglycerol -0.55+/-0.2 in the diabetic group and -0.92+/-0.36 in the nondiabetic group; b) VLDL: -0.11+/-0.04 in the diabetic group and -0.18+/-0.07 in the nondiabetic group.
• We conclude that pharmacological doses of biotin decrease hypertriglyceridemia.

Uncombable hair syndrome: observations on response to biotin and occurrence in siblings with ectodermal dysplasia

• https://www.jaad.org/article/S0190-9622(85)70150-8/abstract
• https://pubmed.ncbi.nlm.nih.gov/4031156/
• Three children are reported with uncombable hair syndrome, consisting of slow-growing, straw-colored scalp hair that could not be combed flat.
• Oral biotin, 0.3 mg three times a day, produced significant improvement after 4 months in one patient, with increased growth rate and with strength and combability of the hair, although the triangular shape remained.
• The other two patients were unique in having associated ectodermal dysplasia. Their hair slowly improved in appearance and combability over 5 years without biotin therapy.

Biotin deficiency in an infant fed with amino acid formula

• https://onlinelibrary.wiley.com/doi/10.1111/j.1346-8138.2005.tb00758.x
• We report a 5-month-old Japanese infant with typical skin lesions who had been diagnosed as a neonate with dyspepsia and fed only an amino acid formula. Serum and urine levels of biotin were below the normal range, but zinc and biotinidase were within normal range
• Daily oral supplementation with 1 mg of biotin resulted in dramatic improvement of the periorificial dermatitis and hair growth together with a complete disappearance of the organic aciduria.
• Our case shows that the characteristic skin manifestations are the most important clue to the diagnosis of biotin deficiency and demonstrated that urinary excretion of biotin and organic aciduria, rather than the serum concentration of biotin, are the sensitive indicators for evaluating the patient's status of biotin deficiency.

The Lowdown on Biotin for Kids: Are Supplements Necessary?

• https://www.llamanaturals.com/blogs/vitamins-and-supplements/biotin-for-kids
• Biotin helps your little one’s body produce energy. Food is made up of three macronutrients — protein, carbohydrates, and fat. When your child eats a meal, these macronutrients need to be broken down by specific enzymes so the body can use them. Those enzymes need biotin in order to function. For example, protein needs to be broken down into amino acids, which are then used to build muscles, bones, and organs, as well as for energy, among other things.
• Biotin is involved in managing cognitive and nervous system function — along with other B vitamins — and there’s some research showing that biotin is likely involved in fetal development and the function of the immune system too.

Ingredient #13: Pantothenic

• Pantethine, a derivative of vitamin B5, favorably alters total, LDL and non-HDL cholesterol in low to moderate cardiovascular risk subjects eligible for statin therapy: a triple-blinded placebo and diet-controlled investigation
• https://www.dovepress.com/pantethine-a-derivative-of-vitamin-b5-favorably-alters-total-ldl-and-n-peer-reviewed-fulltext-article-VHRM
• A total of 32 subjects were randomized to pantethine (600 mg/day from weeks 1 to 8 and 900 mg/day from weeks 9 to16) or placebo. Compared with placebo, the participants on pantethine showed a significant decrease in total cholesterol at 16 weeks (P=0.040) and LDL-C at 8 and 16 weeks (P=0.020 and P=0.006, respectively), and decreasing trends in non-high-density lipoprotein cholesterol at week 8 and week 12 (P=0.102 and P=0.145, respectively) that reached significance by week 16 (P=0.042).
• An 11% decrease in LDL-C from baseline was seen in participants on pantethine, at weeks 4, 8, 12, and 16, while participants on placebo showed a 3% increase at week 16. This decrease was significant between groups at weeks 8 (P=0.027) and 16 (P=0.010).
• The homocysteine levels for both groups did not change significantly from baseline to week 16. Coenzyme Q10 significantly increased from baseline to week 4 and remained elevated until week 16, in both the pantethine and placebo groups. After 16 weeks, the participants on placebo did not show significant improvement in any CVD risk end points
• This study confirms that pantethine lowers cardiovascular risk markers in low to moderate CVD risk participants

Effects of supplemental pantothenic acid on wound healing: experimental study in rabbit

• https://www.sciencedirect.com/science/article/abs/pii/S0002916523348032?via%3Dihub
• The supplemented group was injected with pentothenate (20 mg/kg of body weight/24 h) for three weeks and compared to a placebo group (0.5 ml of distilled water). Deficient animals were fed with a pantothenate free diet also for three weeks.
• The average urinary elimination in the pantothenic acid group was significantly higher as far as the pantothenate supplemented group was concerned, while the deficient group showed no significant decrease when compared to controls. Chronic pre- and postoperative pantothenic acid supplementation significantly increased aponeurosis strength after surgery; it improved slightly, but not significantly the strength of the skin
• These data suggest that pantothenic acid induces an accelerating effect of the normal healing process. The mechanism responsible for this improvement seems to be an increase in cellular multiplication during the first postoperative period.

Ingredient #14: Calcium

Increasing dietary calcium intake of children and their parents: a randomised controlled trial

• https://www.cambridge.org/core/journals/public-health-nutrition/article/increasing-dietary-calcium-intake-of-children-and-their-parents-a-randomised-controlled-trial/640EE327727E3570F913E4871F92F144
• Approximately 25 % of Canadian children aged 4–8 years fail to meet the recommended dietary allowance (RDA) of calcium (Ca).
• A total of 239 parents (93 % mothers) of children aged 4–10 years who consumed less than the RDA of Ca were randomly assigned in a 1:1 allocation ratio.
• There was a significant increase in total Ca intake and Ca from dairy for children at weeks 8, 34 and 52 (P ≤ 0·001) in both conditions.

Calcium Intake and Metabolism in Infants and Young Children: A Systematic Review of Balance Studies for Supporting the Development of Calcium Requirements

• https://www.sciencedirect.com/science/article/pii/S2161831323000261?via%3Dihub
• Studies in children aged 0–4 y to address key questions on calcium loss and absorption/retention identified by an expert group developing calcium requirements.
• 23 studies (15 mass balance; 8 isotope) with 485 total participants were included. Only 3 studies were of children >6 mo.
• The random-effects model meta-regression on 42 mass balance study arms showed an average net calcium retention of 40.4% among infants aged 0–6 mo (β = 0.404 [95% CI: 0.302, 0.506]).
• Isotope studies suggested calcium intake of 240 to 400 mg/d may promote optimal calcium absorption with minimal loss, and intake from human milk may lead to greater absorption and retention efficacy than formula or solid foods. Most studies had low risk of bias.

Calcium: The Bone Builder Kids & Teens Need

• https://www.healthychildren.org/English/healthy-living/nutrition/Pages/calcium-the-bone-builder-kids-and-teens-need.aspx
• As children grow, they need calcium and other nutrients to build strong bones and a healthy body
• The body's need for calcium is at its highest point between the ages of 9 years and 18 years old. Not getting enough calcium during this can affect bone strength later in life.
• If somebody doesn't get enough calcium, their bones will weaken. This is because the body will take calcium out of the bones to use elsewhere if needed.
• When we are young, our bodies can store calcium in our bones. As we get older, we lose the ability to store calcium in our bones. By the time a child reaches young adulthood, their bones reach their peak bone density. That means their bones are as dense (or packed) with calcium as they will get—for life. After that, the body mainly withdraws calcium from what is stored in our bones.
• People who do not have enough calcium stored in their bones can get osteoporosis when they age. Osteoporosis is a disease that can make bones so fragile that they break from the stress of just bending over.

Ingredient #15: Iron

The Importance Of Sufficient Iron Intake For Kids

• https://drgreenmom.com/the-importance-of-sufficient-iron-intake-for-kids-plus-kid-approved-recipes/
• Iron is vital for optimal oxygen transport and energy production. Iron deficiency is associated with impaired neurocognitive development and immune function in young children (1). Among children aged 1 to 5, approximately 7.1% exhibit deficient iron levels.
• Iron is an essential mineral that holds an important role in the growth and development of children (3). Iron is necessary for various bodily functions, including the production of hemoglobin, a protein in red blood cells that carries oxygen from the lungs to the rest of the body. This oxygen exchange fuels vital bodily functions, enabling children to thrive physically, mentally, and emotionally.
• Iron is a component of the enzymes that play a role in the synthesis of collagen, an essential protein for maintaining the structural integrity of tissues like skin, bones, and blood vessels. Iron also aids in the production of neurotransmitters that facilitate communication between nerve cells in the brain (4). Furthermore, iron supports the immune system, aiding in the prevention of infections (5). Adequate iron levels are needed for cognitive development, concentration, and overall energy levels (6). In fact, one of the first noticeable symptoms of iron deficiency is often reduced energy.
• https://kidshealth.org/en/parents/iron.html
• Infants who breastfeed tend to get enough iron from their mothers until 4–6 months of age. Around this time, iron-rich foods like fortified cereal and puréed meats are usually introduced. Breastfed babies who don't get enough iron should be given iron drops prescribed by their doctor. Babies given iron-fortified formula do not need added iron.
• Infants ages 7–12 months need 11 milligrams of iron a day.
• Toddlers ages 1–3 years need 7 milligrams of iron each day. Kids ages 4–8 years need 10 milligrams while older kids ages 9–13 years need 8 milligrams.
• Teen boys should get 11 milligrams of iron a day and teen girls should get 15 milligrams. (Adolescence is a time of rapid growth and teen girls need additional iron to replace what they lose monthly when they begin menstruating.)
• Young athletes who regularly engage in intense exercise tend to lose more iron and may need extra iron in their diets.

Iron-deficiency anemia

• https://www.ucsfbenioffchildrens.org/conditions/iron-deficiency-anemia
• A child who is diagnosed with iron deficiency anemia has a decreased number of red blood cells in his or her blood due to a lack of iron
• Red blood cells bring oxygen to body tissues, so having insufficient numbers of red blood cells means that muscles and organs may not have enough oxygen to function fully. Low iron levels in children can cause a decreased attention span, reduced alertness and learning difficulties. Since iron is also used by cells other than blood cells, such as brain cells, low iron can also interfere with brain development in the first years of life.

Ingredient #16: Iodine

Iodine in children and teenagers

• https://www.iodomarin.health/children
• Iodine deficiency can have some negative effects throughout childhood and adolescence. Up to 15 percent of schoolchildren in iodine deficiency regions experience difficulties in studying.
• Furthermore the risk for the development of mental retardation in these regions is two times higher than in other regions. Also a moderate iodine deficiency reduces the mental potential of the population by an average of 10 to 15%.
• This shows clearly how important it is to maintain the health of young people because they represent the future reproductive, intellectual, economic, social, political and cultural potential of our society.
• Another consequence of long-standing iodine deficiency in children can be the development of a so-called hyperthyroidism in multinodular goitres, a non-tumour enlargement of the thyroid gland. Symptoms of this hyperthyroidism can be for example a rapid heart rate, weight loss, sweating, difficulties in sleeping, nervousness, and anxiety.
• recommend a daily intake of 90 μg for children up to the age of 59 months:
• recommend a daily intake 120 μg for children from 6 to 12 years.
• recommend a daily intake 150 μg for teenagers above 12 years.
• A clinical study has shown that giving iodine supplements like Iodomarin® to children or teenagers with mild iodine deficiency can improve their reasoning abilities and overall cognitive function. In children living in iodine-deficient areas, iodine supplements seem to improve both physical and mental development.
• But also if your child doesn’t suffer from iodine deficiency at the moment, prophylactic administration of iodine supplement could be useful as iodine contributes to the normal growth of children and to normal cognitive function.

Iodine and your health

• https://www.healthdirect.gov.au/iodine
• Iodine helps the thyroid gland, in the neck, to make the hormone thyroxine. Thyroxine controls many of the ways certain body cells work.
• Thyroxine is important for the growth of bones and nerves, and affects how proteins, fats and carbohydrates are used in the body (metabolism).
• Iodine is especially important before birth and in babies and young children. It is essential for the development of the brain and nervous system, the 5 senses, alertness and coordination. Iodine deficiency is the most common worldwide cause of preventable mental retardation.

What Does Iodine Do for the Body?

• https://hiyahealth.com/blogs/news/how-much-iodine-for-kids-per-day
• The body cannot make thyroid hormones without iodine. These hormones are essential for more than just thyroid function. The body also uses the same hormones for brain development and bone development. Without micronutrients like iodine, children cannot grow.
• The thyroid is responsible for regulating metabolism, which is one of the most critical processes in the body. Metabolism is responsible for processing every nutrient, vitamin, and mineral you eat. It also helps the body create energy from food.
• Iodine is crucially essential for pregnant people, as babies need iodine to grow to term. It’s equally as crucial during infancy when children are growing at a rapid rate. If you’re pregnant or breastfeeding, it’s essential to receive adequate amounts of dietary iodine.
• People with iodine deficiency often feel very cold. Their skin may become dry and flaky, and they may lose their hair. Over time, iodine deficiency results in cognitive decline. People with iodine deficiency have trouble reading, learning, remembering, and reasoning. This is because thyroid hormones play a key role in brain development. Without sufficient amounts of these hormones, children can become intellectually disabled.
• Children with iodine deficiencies may never reach their full intellectual capacities. This type of severe iodine deficiency is normally only seen in the developing world, and international organizations for the health and welfare of children have taken steps to provide more sources of iodine to children who may be at risk.

Ingredient #17: Magnesium

Boost exercise performance

• Magnesium status and the physical performance of volleyball players: effects of magnesium supplementation
• https://www.tandfonline.com/doi/abs/10.1080/02640414.2013.828847
• Twenty-five professional male volleyball players were assigned randomly to experimental (350 mg Mg · d(-1), 4 weeks) and control groups (500 mg maltodextrin · d(-1), 4 weeks) maintaining inter-group homogeneity of urinary magnesium
• Levels of erythrocyte and urinary magnesium and creatine kinase activity and VO2 max remained within normal ranges in both groups. Plasma magnesium decreased significantly only within the experimental group.
• Significant decreases in lactate production and significant increases (of up to 3 cm) in countermovement jump and countermovement jump with arm swing values were detected in the experimental group following magnesium supplementation, but not in the control group at T1.
• It is concluded that magnesium supplementation improved alactic anaerobic metabolism, even though the players were not magnesium-deficient.

Combats depression

• Effect of magnesium supplementation on depression status in depressed patients with magnesium deficiency
• https://www.sciencedirect.com/science/article/abs/pii/S0899900716302441?via%3Dihub
• Sixty depressed people suffering from hypomagnesemia participated in this trial. The individuals were randomly categorized into two groups of 30 members; one receiving two 250-mg tablets of magnesium oxide (MG) daily and the other receiving placebo (PG) for 8 wk
• At the end of intervention, 88.5% of the MG and 48.1% of the PG (P = 0.002) had a normal level of magnesium. The mean changes of serum magnesium were significantly different across the two groups
• After the intervention, the mean Beck score significantly declined. However, in the MG, this reduction was more significant than in the PG (P = 0.02), so that the mean changes in this group experienced 15.65 ± 8.9 reduction, but in the PG, it declined by 10.40 ± 7.9.
• Daily consumption of 500 mg magnesium oxide tablets for ≥8 wk by depressed patients suffering from magnesium deficiency leads to improvements in depression status and magnesium levels

Supports healthy blood sugar levels

• Association of magnesium consumption with type 2 diabetes and glucose metabolism
• https://onlinelibrary.wiley.com/doi/10.1002/dmrr.3243
• Twenty-six publications involving 35 cohorts were included in the analysis. Compared to the lowest magnesium intake, the highest level was associated with a 22% lower risk for T2D; the risk was reduced by 6% for each 100 mg increment in daily magnesium intake.
• Additional analysis of 26 RCTs (1168 participants) was performed, revealing that magnesium supplementation significantly reduced the fasting plasma glucose (FPG) level (SMD, -0.32 [95% CI, -0.59 to -0.05], 2-hour oral glucose tolerance test (2-h OGTT) result (SMD, -0.30 [-0.58 to -0.02]), fasting insulin level (SMD, -0.17 [-0.30 to -0.04]), homeostatic model assessment-insulin resistance (HOMA-IR) score (SMD, -0.41 [-0.71 to -0.11]), triglyceride (TG) level, systolic blood pressure (SBP) and diastolic blood pressure (DBP).
• magnesium intake has an inverse dose-response association with T2D incidence, and supplementation appears to be advisable in terms of glucose parameters in T2D/high-risk individuals.

Promotes heart health

• The Effect of Magnesium Intake on Stroke Incidence: A Systematic Review and Meta-Analysis With Trial Sequential Analysis
• https://www.frontiersin.org/journals/neurology/articles/10.3389/fneur.2019.00852/full
• Fifteen studies with low bias involving 18 cohorts were entered into this study.
• The summary relative risk (RR) was significantly reduced by 11% for total stroke (RR: 0.89 [95% CI, 0.83–0.94]; P < 0.001) and by 12% for ischemic stroke (RR: 0.88 [95% CI, 0.81–0.95]; P = 0.001), comparing the highest magnesium intake category to the lowest.
• The quantitative associations for total and ischemic stroke were robust.
• Importantly, high-risk females who had a body mass index (BMI) ≥25 kg/m2 and who were subjected to a ≥12 y follow-up exhibited a greater decrease in RRs as a result of magnesium intake.
• For each 100 mg/day increase in magnesium, the risk for total stroke was reduced by 2% and the risk for ischemic stroke was reduced by 2%.

Boasts anti-inflammatory benefits

• Effect of Magnesium Supplementation on Plasma C-reactive Protein Concentrations
• https://pubmed.ncbi.nlm.nih.gov/28545353/
• The impact of magnesium supplementation on plasma concentrations of CRP was assessed in 11 studies
• Magnesium treatment was not found to significantly affect plasma concentrations of CRP (WMD: -0.11 mg/L, 95% CI: -0.75, 0.52, p=0.727). When the analysis was stratified to compare subgroups of studies in populations with baseline plasma CRP values of ≤ 3 and > 3 mg/L, a significant reduction of CRP values was observed in the latter subgroup (WMD: -1.12 mg/L, 95% CI: -2.05, -0.18, p=0.019) but not in the former group (WMD: 0.61 mg/L, 95% CI: -0.10, 1.32, p=0.090). The difference between subgroups was statistically significant (p=0.004).
• Results of the present meta-analysis indicated that magnesium supplementation reduces CRP levels among individuals with inflammation (CRP levels > 3 mg/dL)

Helps prevent migraine attacks

Magnesium in Migraine Prophylaxis-Is There an Evidence-Based Rationale?

• https://headachejournal.onlinelibrary.wiley.com/doi/10.1111/head.13217
• Randomized, double-blind, placebo-controlled trials investigating prophylactic magnesium administration in migraineurs aged 18-65 were considered eligible
• five clinical trials fulfilling the selection procedure were found. One out of two Class I evidence trials showed a significant reduction of the number of migraine attacks compared with placebo, while two out of three Class III trials evinced a statistically significant reduction of the primary efficacy parameters compared with placebo.
• This systematic review provides Grade C (possibly effective) evidence for prevention of migraine with magnesium. Prophylactic treatment of migraine by means of high levels of magnesium dicitrate (600 mg) seems to be a safe and cost efficient strategy in clinical use.

Promotes bone health

• Impact of serum magnesium and bone mineral density on systemic fractures in chronic hemodialysis patients
• https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0251912
• BMD and serum magnesium levels were measured in 358 stable outpatients undergoing maintenance hemodialysis therapy
• During the median follow-up period of 36 months, 36 (10.0%) fractures occurred. The cumulative incidence rates of fractures were 17.6% and 5.2% [adjusted hazard ratio (aHR) 2.31, 95% confidence interval (CI) 1.03–5.17, P = 0.030] in the lower (<2.6 mg/dL) and higher (≥2.6 mg/dL) magnesium (Mg) groups, respectively, and 21.2% and 7.3% (aHR 2.59, 95% CI 1.09–6.16, P = 0.027) in the low- and high-BMD groups, respectively.
• The lower-Mg and low-BMD group had a 9.21-fold higher risk of fractures (95% CI; 2.35–47.00; P = 0.0010) than the higher-Mg and high-BMD group. Furthermore, adding both magnesium levels and lumbar spine BMD levels to the established risk factors significantly improved the prediction of fractures (C-index: 0.784 to 0.830, p = 0.041).
• The combination of serum magnesium and lumbar spine BMD can be used for fracture risk stratification and synergistically improves the prediction of fractures in CKD patients.

Ingredient #18: Zinc

Boost your immune system

• Zinc lozenges and the common cold: a meta-analysis comparing zinc acetate and zinc gluconate, and the role of zinc dosage
• https://journals.sagepub.com/doi/10.1177/2054270417694291
• Placebo-controlled zinc lozenge trials, in which the zinc dose was > 75 mg/day. The pooled effect of zinc lozenges on common cold duration was calculated by using inverse-variance random-effects method.
• Seven randomised trials with 575 participants with naturally acquired common colds. Duration of testing last the duration of a common cold.
• The mean common cold duration was 33% (95% CI 21% to 45%) shorter for the zinc groups of the seven included trials. Three trials that used lozenges composed of zinc acetate found that colds were shortened by 40% and four trials that used zinc gluconate by 28%. The difference between the two salts was not significant: 12 percentage points (95% CI: −12 to + 36). Five trials used zinc doses of 80–92 mg/day, common cold duration was reduced by 33%, and two trials used zinc doses of 192–207 mg/day and found an effect of 35%. The difference between the high-dose and low-dose zinc trials was not significant: 2 percentage points (95% CI: −29 to + 32).
• There is no evidence that zinc doses over 100 mg/day might lead to greater efficacy in the treatment of the common cold

Accelerates wound healing

• The effects of zinc supplementation on wound healing and metabolic status in patients with diabetic foot ulcer: A randomized, double-blind, placebo-controlled trial
• https://onlinelibrary.wiley.com/doi/10.1111/wrr.12537
• The current randomized, double-blind, placebo-controlled trial was conducted among 60 patients (aged 40–85 years old) with grade 3 diabetic foot ulcer.
• Participants were randomly divided into two groups (30 participants in each group) to take either 220 mg zinc sulfate supplements containing 50 mg elemental zinc or placebo daily for 12 weeks. After the 12-week intervention, compared with the placebo, zinc supplementation was associated with significant reductions in ulcer length (−1.5 ± 0.7 vs. −0.9 ± 1.2 cm, p = 0.02) and width (−1.4 ± 0.8 vs. −0.8 ± 1.0 cm, p = 0.02)
• Zinc supplementation for 12 weeks among diabetic foot ulcer patients had beneficial effects on parameters of ulcer size and metabolic profiles.

Helps treat acne

• Serum zinc levels and efficacy of zinc treatment in acne vulgaris: A systematic review and meta-analysis
• https://onlinelibrary.wiley.com/doi/10.1111/dth.14252
• Subjects with acne had significantly lower serum zinc levels compared to controls.
• Patients who were treated with zinc had a significant improvement in mean inflammatory papule count compared to those who were not treated with zinc.
• There was no significant difference in the incidence of side effects in zinc supplementation vs comparators. Acne patients have decreased serum zinc levels.
• Zinc is effective for the treatment of acne, particularly at decreasing the number of inflammatory papules, when used as monotherapy or as an adjunctive treatment.

Decreases inflammation

• Zinc decreases C-reactive protein, lipid peroxidation, and inflammatory cytokines in elderly subjects: a potential implication of zinc as an atheroprotective agent
• https://www.sciencedirect.com/science/article/pii/S0002916523017318?via%3Dihub
• We recruited 40 healthy elderly subjects (aged 56–83 y) and randomly assigned them to 2 groups. One group was given an oral dose of 45 mg zinc/d as a gluconate for 6 mo. The other group was given a placebo. Cell culture models were conducted to study the mechanism of zinc as an atheroprotective agent
• After 6 mo of supplementation, the intake of zinc, compared with intake of placebo, increased the concentrations of plasma zinc and decreased the concentrations of plasma high-sensitivity C-reactive protein (hsCRP), interleukin (IL)-6, macrophage chemoattractant protein 1 (MCP-1), vascular cell adhesion molecule 1 (VCAM-1), secretory phospholipase A2, and malondialdehyde and hydroxyalkenals (MDA+HAE) in elderly subjects
• Regression analysis showed that changes in concentrations of plasma zinc were inversely associated with changes in concentrations of plasma hsCRP, MCP-1, VCAM-1, and MDA+HAE after 6 mo of supplementation
• In cell culture studies, we showed that zinc decreased the generation of tumor necrosis factor-α, IL-1β, VCAM-1, and MDA+HAE and the activation of nuclear transcription factor κB and increased antiinflammatory proteins A20 and peroxisome proliferator–activated receptor-α in human monocytic leukemia THP-1 cells and human aortic endothelial cells compared with zinc-deficient cells.

Ingredient #19: Copper

Copper as Dietary Supplement for Bone Metabolism

https://www.mdpi.com/2072-6643/13/7/2246

• This review included 10 eligible studies: five studies concerned copper blood levels, one study concerned daily copper intake, and four studies concerned copper supplementation
• The two studies that analyzed the integration of copper (2.5–3 mg/day) only showed good results in terms of slowing down bone mineral loss and reducing resorption markers, confirming the effectiveness of copper supplementation on bone metabolism

Serum and dietary zinc and copper in Iranian girls

• https://www.sciencedirect.com/science/article/abs/pii/S0009912017307981?via%3Dihub
• A total of 408 healthy girls, aged 12–18 years old, were included in our study. Serum zinc and copper concentrations were measured by flame atomic absorption (Varian AA240FS) and zinc and copper intake were assessed using a 3-day dietary record
• The correlation between serum and dietary copper approached significance (r = −0.094, p = 0.056). The mean serum zinc and copper concentrations were 14.61 ± 2.71 μmol/L and 19.48 ± 8.01 μmol/L respectively.
• Height, total cholesterol (TC) and low-density lipoprotein (LDL) were positively correlated with serum copper concentration. Subjects with high serum copper concentrations (>24 μmol/L) were found to have a significantly higher fasting blood glucose (FBG) compared to subjects with normal, or low serum copper concentrations (p = 0.033).
• Girls who were in the 5th percentile or greater for height were found to have higher serum copper concentrations than girls in other height categories

Why Do Children Need Copper?

• https://dailyjolly.co/blogs/nutrition/what-is-the-importance-of-copper-for-kids
• Maintains skin health: Copper is vital for maintaining skin health in children because it enhances the production of elastin (provides resilience and elasticity to the skin) and collagen (gives structure and strength to the skin).
• One scientific study has found that due to its strong anti-fungal and anti-microbial properties, this mineral is woven into socks to treat foot infections in athletes. These socks are also good for preventing wounds, ulcers, and cuts. Another recent study has shown that sleeping on pillowcases that contain copper oxides can improve your overall skin appearance and reduce fine wrinkles.
• Supports brain development: Research has shown that copper is a strong brain stimulant that is linked with higher thought processes. It enhances creativity, opens neural pathways, and supports brain functioning in children. In short, it makes your child’s brain more efficient and fast- who doesn’t want that?!
• Promotes blood circulation: Copper promotes the absorption of iron in your child’s body and releases it when needed by essential organs, such as the liver. It improves blood circulation and regulates blood flow by maintaining the iron levels in your child’s body. It also aids the body in maintaining the oxidation of internal organs and a healthy count of red blood cells.
• Improves digestion: This essential trace mineral is great for healthy metabolism and proper digestion in kids. Several studies have depicted that copper is effective in reducing inflammation in the stomach, killing pathogenic microbes that are present in water, and promoting the digestion of food.
• Prevents bone loss: Recent research has shown that in combination with other minerals, including calcium, manganese, and zinc, copper prevents bone loss and supports bone formation in children. This is because it has strong collagen-forming and bone-strengthening properties that support bone health and connective tissues.
• Contains anti-inflammatory properties: Copper has natural anti-inflammatory properties and can provide relief from aches and pains that are caused by inflamed joints.

Ingredient #20: Inositol

Double-blind, controlled trial of inositol treatment of depression

• https://ajp.psychiatryonline.org/doi/abs/10.1176/ajp.152.5.792
• 12 g/day of inositol (N = 13) or placebo (N = 15) was administered to depressed patients for 4 weeks.
• The overall improvement in scores on the Hamilton Depression Rating Scale was significantly greater for inositol than for placebo at week 4. No changes were noted in hematology or in kidney or liver function.

Double-blind, placebo-controlled, crossover trial of inositol treatment for panic disorder

• https://ajp.psychiatryonline.org/doi/abs/10.1176/ajp.152.7.1084
• Twenty-one patients with panic disorder with or without agoraphobia completed a double-blind, placebo-controlled, 4-week, random-assignment crossover treatment trial of 12 g/day of inositol.
• The frequency and severity of panic attacks and the severity of agoraphobia declined significantly more after inositol than after placebo administration. Side effects were minimal.
• inositol's efficacy, the absence of significant side effects, and the fact that inositol is a natural component of the human diet make it a potentially attractive therapeutic for panic disorder.

Double-blind, controlled, crossover trial of inositol versus fluvoxamine for the treatment of panic disorder

• https://journals.lww.com/psychopharmacology/abstract/2001/06000/double_blind,_controlled,_crossover_trial_of.14.aspx
• A double-blind, controlled, random-order crossover study was undertaken to compare the effect of inositol with that of fluvoxamine in panic disorder.
• Twenty patients completed 1 month of inositol up to 18 g/day and 1 month of fluvoxamine up to 150 mg/day.
• In the first month, inositol reduced the number of panic attacks per week (mean and SD) by 4.0 (2) compared with a reduction of 2.4 (2) with fluvoxamine (p = 0.049).
• Nausea and tiredness were more common with fluvoxamine (p = 0.02 and p = 0.01, respectively). Because inositol is a natural compound with few known side effects, it is attractive to patients who are ambivalent about taking psychiatric medication

A randomized clinical trial of high eicosapentaenoic acid omega-3 fatty acids and inositol as monotherapy and in combination in the treatment of pediatric bipolar spectrum disorders: a pilot study

• https://www.psychiatrist.com/jcp/randomized-clinical-trial-high-eicosapentaenoic-acid/
• Participants were children 5-12 years of age meeting DSM-IV diagnostic criteria for bipolar spectrum disorders (bipolar I or II disorder or bipolar disorder not otherwise specified [NOS]) and displaying mixed, manic, or hypomanic symptoms.
• Subjects were randomized to 1 of 3 treatment arms: inositol plus placebo, omega-3 fatty acids plus placebo, and the combined active treatment of omega-3 fatty acids plus inositol.
• Twenty-four subjects were exposed to treatment (≥ 1 week of study completed) (inositol [n = 7], omega-3 fatty acids [n = 7], and omega-3 fatty acids plus inositol [n =10]). Fifty-four percent of the subjects completed the study.
• Subjects randomized to the omega-3 fatty acids plus inositol arm had the largest score decrease comparing improvement from baseline to end point with respect to the Young Mania Rating Scale (P < .05).
• treatment of omega-3 fatty acids plus inositol reduced symptoms of mania and depression in prepubertal children with mild to moderate bipolar spectrum disorders

Role of Inositols and Inositol Phosphates in Energy Metabolism

• https://www.mdpi.com/1420-3049/25/21/5079
• MORE INFO HERE

Ingredient #21: Vitamin K2

• The Impact of Vitamin K2 (Menaquionones) in Children’s Health and Diseases: A Review of the Literature
• https://www.mdpi.com/2227-9067/9/1/78
• Vitamin K2 activates vitamin K-dependent proteins that support many biological functions, such as bone mineralization, the inhibition of vascular stiffness, the improvement of endothelial function, the maintenance of strong teeth, brain development, joint health, and optimal body weight
• Vitamin K2 as menaquinone-7 (MK-7) has a documented history of safe and effective use. The lack of adverse effects of MK-7 makes it the ideal choice for supplementation by pregnant and nursing women and children, both healthy and suffering from various malabsorptions and health disorders, such as dyslipidemia, diabetes, thalassemia major (TM), cystic fibrosis (CF), inflammatory bowel diseases (IBD), and chronic liver diseases.

Oral Consumption of Vitamin K2 for 8 Weeks Associated With Increased Maximal Cardiac Output During Exercise

• https://pubmed.ncbi.nlm.nih.gov/28646812/
• The purpose of this study was to determine if 8 wk of dietary supplementation with Vitamin K2 could alter cardiovascular responses to a graded cycle ergometer test
• The study took place in the Applied Physiology Laboratory of the Department of Biological Sciences at the University of North Texas (Denton, TX, USA)
• Participants were randomly assigned either to a control group that received a rice flour placebo or to an intervention group that received vitamin K2. For weeks 1 to 4, participants received 300 mg/d; for weeks 5 to 8, they received 150 mg/d. Subjects assigned to the control group received similar doses to mirror the intervention group. Subjects consumed the supplements during an 8-wk period while they maintained their typical exercise habits
• Vitamin K2 supplementation was associated with a 12% increase in maximal cardiac output, with P = .031, with a trend toward an increase in heart-rate AUC, with P = .070. No significant changes occurred in stroke volume.
• vitamin K2 supplementation has previously been reported to improve cardiovascular function in diseased patients, to the research team's knowledge, the current study is the first to report its potential in active individuals

Proper Calcium Use: Vitamin K2 as a Promoter of Bone and Cardiovascular Health

• https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4566462/