Exposure to toxins may have detrimental effects on humans and animals, even at low concentrations. Specific probiotic and bacterial strains may have properties that enable them to bind to toxins we are exposed to in our environment, such as food and water. Different strains vary in their ability to bind and detoxify, often times relying on pH, contact time, and viability on the binding capacities. Below are 3 bacterial strains and a summary of their mechanisms of action on human biochemistry regarding detoxification.
Mycotoxin Degradation – Mycotoxins are secondary metabolites produced by fungi, and are capable of producing disease and death in humans (Chlebicz & Slizewska, 2019). Humans are exposed to mycotoxins while consuming plant foods such as nuts (hazelnut, almonds, pistachios), peanuts, grains and some fruits. They are also exposed to them in the environment such as often reported in mold that is found in homes that have been water damaged. Aflatoxins are secondary metabolites of Aspergillus flavus and Aspergillus parasiticus, and it has been estimated that 4.5 billion of the world’s population is exposed to aflatoxins (Wild & Gong, 2010). The aflatoxins occur mostly in tropical regions with high humidity and temperature. They accumulate post-harvest when food commodities are stored under conditions that promote fungal growth. The naturally occurring aflatoxins are AFB1, AFB2, AFG1 and AFG2, with AFB1 the most abundant, toxic and carcinogenic, and are linked to liver cancer. “However, in agriculture, other adverse effects, including toxicity, growth and immune impairment, have been widely reported and these end points are rightly of increasing focus in studies of exposed people” (Wild & Gong, 2010).
Aflatoxin B1 (AFB1) is considered to possess the highest toxicity among various types of secondary metabolites produced by a larger number of Aspergillus spp., and classified as a Group I carcinogen for humans by the International Agency for Research on Cancer (Chlebicz & Slizewska, 2019). It has been reported that AFB1 could induce growth retardation, liver cancer, and may suppress immunity. Relevant studies indicated that AFB1was mostly metabolized by cytochrome P450 (CYP 450) enzyme systems after being absorbed in the GI tract. “Subsequently, under the action of CYP 450, including CYP1A2 and CYP 3A4, AFB1 was transformed to exo-AFB1-8,9-epoxide (AFBO), which could bind to DNA, proteins, and other critical cellular macromolecules to exert its carcinogenic effect” (Chlebicz & Slizewska, 2019).
Below are two probiotics that show promise in detoxification of mycotoxins:
- Saccharomyces cerevisiae var boulardii- (note the authors indicate that since S. cerevisiae and S. boulardii are closely similar in molecular structure, they should not be viewed as separate species taxonomically, so they have been renamed as saccharomyces cerevisiae van boulardii). Inhibition of mycotoxin absorption in the GI tract is one of the mechanisms of action of this strain. The mechanism of detoxification by yeast is due to the adhesion of mycotoxins to cell-wall components. In addition, this strain can biodegrade mycotoxins (such as AFB1) to prevent adsorption of these components inside the intestines on those who consume the food that is contaminated with the aflatoxin. As a side note, Saccharomyces cerevisiae var boulardii can also degrade phytates that are also found on many of the same foods that mycotoxins are found, and this may improve adsorption of iron, zinc, magnesium and phosphorus binding (Moslehi-Jenabian, Pedersen, & Jespersen, 2010). This could be viewed as a secondary mechanism involved in detoxification.
- L. plantarum—Lactobacillus species are also able to bind mycotoxins. Via hydrophobic interactions, they are able to bind to mostly cell wall peptidoglycans, polysaccharides and teichoic acid (Chlebicz & Slizewska, 2019). L. plantarum has demonstrated to have good AFB1binding ability in vitro. It can also “increase fecal AFB1excretion, reduce lipid peroxidation, and reverse antioxidant defense systems to alleviate AFB1 toxicity” (Chlebicz & Slizewska, 2019). L. plantarum may also play a role in the suppression of CYP1A2 and CYP3A4 expression to enhance glutathione-conjugating activity and promote detoxification (Chlebicz & Slizewska, 2019). It has been reported that some lactic acid bacteria such as L. plantarum can remove AFB1 or have protective effects against AFB1. Some relevant studies demonstrated that lactobacilli could inhibit the production of aflatoxin as well as the growth of Aspergillus spp. (Huang et al., 2017). L. plantarum also demonstrates strong free radical scavenging activities and can improve antioxidant status, protecting against the effects of AFB1. “L. plantarum might also act as a biological barrier in the intestine under normal conditions, thereby reducing the bioavailability of AFB1 ingested orally and hence avoiding its toxic effects” (Chlebicz & Slizewska, 2019). I attached a chart that demonstrates some of the mechanisms of L. plantarum on detoxification of AFB1., which includes increasing AFB1 excretion, decreasing AFB1 epoxidation catalyzed by CYP1A2 and CYP3A4, coupled with enhancing the activities of different antioxidant enzymes and GST detoxification which are connected with the NrF2 signaling pathway (Chlebicz & Slizewska, 2019).
- Bacillus subtilis– This spore forming species of bacteria had some interesting mechanisms in detoxification.
Cypermethrin belongs to a group of synthetic pyrethroid insecticides which widely used in agriculture, forestry, horticulture, public health and households for the protection of textiles and to check pest infestation (Gangola, Sharma, Bhatt, Khati, & Chaudhary, 2018). . Cypermethrin is also constitute common ingredients of household insecticides (Gangola et al., 2018). Cypermethrin is an environment pollutant because of its widespread use and toxicity. Persistence may lead to serious damage to non-target organisms and various ecosystem (Gangola et al., 2018). Metabolism of cypermethrin is important because cypermethrin possess antimicrobial activities hence it prevents the beneficial microflora.
The mechanism of action is the laccase enzyme that can degrade the pesticide. Bacillus subtilis strain demonstrated to completely metabolize cypermethrin in just 15 days under laboratory conditions. The bacterial isolate harbors the metabolic pathway for the detoxification of the cypermethrin. It can also completely degrades cypermethrin without leaving any persistent or toxic metabolite (Gangola et al., 2018).
Heavy metals (Syed & Chinthala, 2015)
It is estimated that over one billion human beings are currently exposed to elevated concentrations of toxic metals and metalloids in the environment. It is also estimated that several million people may be suffering from subclinical metal poisoning. “In addition, adverse effect of heavy metals includes suppression of the immune system and carcinogenicity, neurotoxicity, mainly in children, and inhibition of the activity of some critical enzymes related to synthesis of vital biomolecules along with accumulation in the body of different organisms causing biomagnifications” (Syed & Chinthala, 2015). B. subtilis has greater ability to bind metals than Gram-negative ones due to their different cell wall structures (Cai et al., 2018). Interestingly, bacterial isolates of B. subtilis showed significant biosorption of lead. Heavy metal biosorption is the ability of bacterial cells or components to adsorb, chelate, or precipitate metal ions in the solution into insoluble particles or aggregates which can be removed either by sedimentation or filtration from the solution. Lead biosorption modifies groups like carboxyl, hydroxyl, and amino where other metal ions cannot compete offering it more affinity. The main agents in the uptake of heavy metals by B. subtilis are carboxyl groups, the sources of which are the teichoic acids associated with the peptidoglycan layers of the cell wall (Cai et al., 2018).
Cai, Y., Li, X., Liu, D., Xu, C., Ai, Y., Sun, X., . . . Yu, H. (2018). A Novel Pb-Resistant Bacillus subtilis Bacterium Isolate for Co-Biosorption of Hazardous Sb(III) and Pb(II): Thermodynamics and Application Strategy. Int J Environ Res Public Health, 15(4). doi:10.3390/ijerph15040702
Chlebicz, A., & Slizewska, K. (2019). In Vitro Detoxification of Aflatoxin B1, Deoxynivalenol, Fumonisins, T-2 Toxin and Zearalenone by Probiotic Bacteria from Genus Lactobacillus and Saccharomyces cerevisiae Yeast. Probiotics Antimicrob Proteins. doi:10.1007/s12602-018-9512-x
Gangola, S., Sharma, A., Bhatt, P., Khati, P., & Chaudhary, P. (2018). Presence of esterase and laccase in Bacillus subtilis facilitates biodegradation and detoxification of cypermethrin. Sci Rep, 8(1), 12755. doi:10.1038/s41598-018-31082-5
Huang, L., Duan, C., Zhao, Y., Gao, L., Niu, C., Xu, J., & Li, S. (2017). Reduction of Aflatoxin B1 Toxicity by Lactobacillus plantarum C88: A Potential Probiotic Strain Isolated from Chinese Traditional Fermented Food “Tofu”. PLoS ONE, 12(1), e0170109. doi:10.1371/journal.pone.0170109
Moslehi-Jenabian, S., Pedersen, L. L., & Jespersen, L. (2010). Beneficial effects of probiotic and food borne yeasts on human health. Nutrients, 2(4), 449-473. doi:10.3390/nu2040449
Syed, S., & Chinthala, P. (2015). Heavy Metal Detoxification by Different Bacillus Species Isolated from Solar Salterns. Scientifica (Cairo), 2015, 319760. doi:10.1155/2015/319760
Wild, C. P., & Gong, Y. Y. (2010). Mycotoxins and human disease: a largely ignored global health issue. Carcinogenesis, 31(1), 71-82. doi:10.1093/carcin/bgp264
For this review, I want to summarize the findings on the dietary carbohydrate to protein ratio and how it may influence body composition and blood lipid profiles in adult women.
There is evidence that older adults experience age-related changes in body composition, such as increase in body fat and decrease in lean body mass (Kim, O’Connor, Sands, Slebodnik, & Campbell, 2016). A moderate energy restricted diet is often an effective way for overweight adults to reduce bodyfat mass, and improve their health profile, but it often comes with the price of a loss of 25% of body mass being lost as lean body mass (Kim et al., 2016). Accumulating data suggests that increased protein content of the diet, in combination with exercise training, can reduce the loss of lean body mass in overweight and obese subjects following a weight loss diet. This preservation of lean body mass has been attributed to the increased level of essential amino acids, especially leucine, provided by the protein (Mettler, Mitchell, & Tipton, 2010).
Current dietary guidelines recommend a daily macro-nutrient intake of 55% carbohydrate, 30% protein and 15% fat (Layman et al., 2003). However, this balance has been challenged by evidence from epidemiological, clinical and experimental studies, reporting that a higher carbohydrate intake can reduce oxidation of body fat and increase blood triglycerides (Layman et al., 2003). In particular, the optimal ratio of carbohydrate to protein has been challenged on the basis of glucose homeostasis in the context of body mass reduction. Under a higher carbohydrate intake, the body has to rely on insulin to metabolize and dispose large quantities of dietary glucose, whereas under lower carbohydrate intakes (<200g per day), the body would rely more on hepatic production to maintain blood glucose via gluconeogenesis or glycogenolysis (Layman et al., 2003).
A study conducted in 2003 by Layman et al (2003), compared the results of a moderate protein and lower carbohydrate intake to a higher carbohydrate with lower protein intake, and the influence on body mass and blood lipids. In this study, the total energy intake, fat and fiber were consistent among the two groups: 1700 kcal/day, total fat intake was 50g/day and total fiber at 20g per day. In the higher protein group (Protein Group) protein intake averaged 125g/day with a carbohydrate intake of 171g/day. The higher carbohydrate group (CHO) consisted of 68g pf protein per day and 239g of carbohydrates. The relative proportions of energy in the Protein Group were 30% protein, 41% carbohydrate and 29% fat with a ratio of carbohydrate to protein (CHO/protein) of 1.4. The proportion in the CHO Group was 16% protein, 58% carbohydrate and 26% fat with a ratio of 3.5 (Layman et al., 2003). Obviously, the cholesterol and saturated fatty acid intake was higher in the Protein group than the CHO group.
The study duration was 10 weeks. The results of the study indicated the following:
- There was not a big change in body weight between the two groups. The Protein Group lost a total weight of 7.53kg and the CHO group lost 6.96kg.
- Changes in body composition indicate the weight loss was mostly bodyfat. The Protein group lost 14.4% of initial body fat, the CHO group lost 12.2% of initial bodyfat. Loss of lean body mass tended to be greater in the CHO Group compared to the Protein Group. When changes in body composition were expressed as a ratio of fat/lean loss, the Protein group achieved a fat/lean loss of 6.36 vs. 3.92 in the CHO group. The higher protein group clearly had a stronger improvement in body composition.
- There were some differences seen in thyroid hormones, blood lipids and fasting and postprandial glucose and insulin levels, but it was not explained in detail as it was not the main objective of this study.
In summary, the results of this study indicate that the positive changes in body composition associated with the higher protein diet may be associated with either targeting of body fat or sparing of muscle protein, or both. For the purposes of improving body composition, a higher protein diet may be effective for adults.
Before I end this summary, I do want to mention I did stumble upon an interesting study in 2016 that indicates that a high protein intake eliminates the weight loss induced improvement of insulin action on postmenopausal women (Smith et al., 2016). This study indicates that a high protein diet can have adverse effects on postprandial insulin sensitivity. According to the authors, “the beneficial effect of 10% weight loss on muscle insulin action (assessed as glucose disposal rate and phosphorylation of AKT in muscle during a HECP) was eliminated by high protein (HP) intake” (Smith et al., 2016). The failure to improve muscle insulin sensitivity in the higher protein group is clinically important, because it reflects a failure to improve a major mechanism involved in the development of T2D. It also indicates more insulin is required in the higher protein group to dispose of a given amount of glucose. This can be due to:
- BCAA’s, particularly leucine, that can impair insulin mediated uptake of glucose through a negative feedback inhibition
- There may be an association of glycine and tryptophan and metabolites of acylcarnitine in the development of insulin resistance, regardless of the amount of circulating amino acid metabolites measured in the serum.
- There may be a metabolic process related to oxidative stress that is expressed in the higher protein group, as evidenced by gene expression of GSTA4 and PRDX3 that are both associated with oxidative stress. These results suggest that the adverse effect of high protein intake on insulin action during weight loss therapy may have been mediated through its effects on oxidative stress because it prevented the WL-induced decrease, and even increased, metabolic pathways involved in oxidative stress response in muscle.
- Both groups had improved liver insulin sensitivity, but the higher protein group experienced a reduction in muscle insulin sensitivity. This is attributed to the fact that protein is a potent insulin secretagogue, which may overcome the adverse effect of protein on insulin sensitivity by increasing the secretion of insulin (Smith et al., 2016).
I must mention however, protein causes greater satiation and has a greater thermogenic effect of feeding than carbohydrate and fat. This alone can lead to greater weight loss with a higher protein than a standard protein diet. “Therefore, the adverse effect of dietary protein on muscle insulin action could be offset by its effect on hepatic insulin sensitivity, insulin secretion and energy balance” (Smith et al., 2016).
In summary, this review demonstrates that the protein content of a weight loss diet can have significant effects on metabolic function and weight loss outcome. I personally believe that diets should be personalized for the individual. A high protein diet is not suitable for everyone. Neither is a high carbohydrate diet. The individual’s needs should be taken into consideration, along with various markers of health that can be measured in a blood chemistry panel, their nutritional needs (such as macronutrient deficiencies) and even nutrigenomics, health predispositions and family history. The one size fits all approach is not appropriate when prescribing nutrition therapy, as the results of these studies also demonstrate.
What do I think? The evidence is good for a higher protein diet, but I wonder if they looked into the glucogenic amino acids and their effect on insulin sensitivity. In my review, I found another journal that indeed indicated that various amino acids can actually decrease insulin sensitivity. Interestingly, it was leucine that was contributing to this change in muscle insulin sensitivity, and that is actually a ketogenic amino acid! If I find the free time at some point, I would love to research the effects of glucogenic and ketogenic amino acids and how they affect insulin sensitivity and type 2 diabetes. I personally have not been a fan of high protein diets. I feel it is too hard on the kidneys, and considering glycine is often a problem with oxalate metabolism, especially in the context B1 deficiency, I feel the risk of kidney stones is too great to recommend high protein across the board (See image). I prefer a more balance approach, with a balance of macronutrients and incorporating intermittent fasting as a way to improve blood lipids and insulin sensitivity.
Kim, J. E., O’Connor, L. E., Sands, L. P., Slebodnik, M. B., & Campbell, W. W. (2016). Effects of dietary protein intake on body composition changes after weight loss in older adults: a systematic review and meta-analysis. Nutr Rev, 74(3), 210-224. doi:10.1093/nutrit/nuv065
Layman, D. K., Boileau, R. A., Erickson, D. J., Painter, J. E., Shiue, H., Sather, C., & Christou, D. D. (2003). A Reduced Ratio of Dietary Carbohydrate to Protein Improves Body Composition and Blood Lipid Profiles during Weight Loss in Adult Women. J Nutr, 133(2), 411-417. doi:10.1093/jn/133.2.411
Mettler, S., Mitchell, N., & Tipton, K. D. (2010). Increased protein intake reduces lean body mass loss during weight loss in athletes. Med Sci Sports Exerc, 42(2), 326-337. doi:10.1249/MSS.0b013e3181b2ef8e
Smith, G. I., Yoshino, J., Kelly, S. C., Reeds, D. N., Okunade, A., Patterson, B. W., . . . Mittendorfer, B. (2016). High-Protein Intake during Weight Loss Therapy Eliminates the Weight-Loss-Induced Improvement in Insulin Action in Obese Postmenopausal Women. Cell Rep, 17(3), 849-861. doi:10.1016/j.celrep.2016.09.047
I was interested in learning more about vitamin E supplementation to address oxidative stress. Dr. Tan wrote a nice summary of Vitamin E in his book “The Truth about Vitamin E”. Vitamin E is a family of eight separate but related molecules, and that includes four tocopherols (delta, gamma, alpha and beta) and four tocotrienols (also delta, gamma, alpha and beta). For many years, the nutrition world focused on tocopherols because it was discovered first. Only in the last decade did tocotrienols start to shine in its delta and gamma molecules and it was found that combined with a healthy lifestyle, it can lower lipids, reduce inflammation, protect the liver, promote bone health, facilitate in eradicating cancer cells and increase survival in cancer patients. In fact, studies demonstrate that the “wrong” form of vitamin E (tocopherols) can actually hinder the body’s ability to absorb the “right form” (tocotrienols).
A few interesting things about tocotrienols:
- Delta tocotrienol help maintain the membrane integrity of the cell membrane to protect cellular functions. Phospholipids, cholesterol and a small amount of protein make up most of the cell membrane, creating a lipid bilayer which is important for water, oxygen and CO2 to cross the membrane while blocking out other larger potentially harmful substances
- It can protect the cell from free radical damage
- Antioxidants like vitamin E (C, A, and selenium and zinc) can give the free radical its own electron without destabilizing the cell. Others include resveratrol, curcumin, astaxanthin, lutein, Coq10. Tocotrienols are well suited to protect the cell membrane because their perfect fit into the lipid bilayer allows them to better protect the lipids within this bilayer from oxidation.
The delta- and gamma-tocotrienols spread out and attach themselves to a variety of cell membranes throughout your body and then start patrolling for free radicals. As soon as they sense one closing in (meaning the free radical attaches to a fatty acid in the cell wall), the tocotrienol molecule releases an electron which re-attaches to the free radical, making the damaged (oxidized) fatty acid in the cell wall whole again. The free radical is stable again and leaves the cell. Put simply, the tocotrienol removes the dysfunctional oxygen from the fatty acid.
What is the difference between tocotrienols and tocopherols? First, they are 40-60 times more potent.
Here are some key differences:
- Tocotrienols have shorter tails that do not anchor deeply into the cell membrane- which allows them to move around the cell 50x faster to intercept free radicals more easily. In contrasts to tocopherols that have a longer tail, anchor deeply into cell membranes, and move more slowly. Because of this it is thought that tocotrienols are 40-60x better at giving one of their electrons to invading free radicals and repairing damage to lipids on membranes
- Tocotrienols have a smaller head and delta tocotrienols have the smallest- allowing them to squeeze in parts of the cell easier, giving them wider access to membranes and increasing their ability to capture more free radicals
- Tocotrienols have unsaturated tails where tocopherols have saturated tails- making them unique in that they have double bonds in their tails and can provide more lipid oxidation protection because of superior bioavailability to cell membranes.
I also want to point out that tocotrienols are great for reducing chronic inflammation. Studies demonstrate that alpha, gamma and delta tocotrienols strongly inhibit NFkB and TNF-a, along with other pro-inflammatory cytokines. “Among the most notable biomarkers to be affected by a 250 mg tocotrienol daily dosage were C-reactive protein (CRP; a predictor for chronic inflammation), nitric oxide (NO), and malondialdehyde (MDA), with decreases of 40%, 40%, and 34%, respectively” (Barrie, nd).
Tocotrienols can increase total antioxidant status. Total antioxidant status also increased by 22%, suggesting that delta-tocotrienol can potentiate endogenous antioxidants. This is great news for the use of tocotrienols for reduce inflammation associated with high cholesterol, CV disease, metabolic syndrome, nonalcoholic fatty liver disease, diabetes and pre-diabetes. It also can play a role in cancer, bone and brain health.
Tocotrienols area great for eye health. Interestingly, delta-tocotrienols may also delay the beginning of cataracts when applied to the eye due to reduced oxidative stress and nitrosative stress to the lenses which are exposed to environmental oxidants. Tocotrienol had a beneficial effect on lens antioxidant enzymes, including superoxide dismutase and catalase, both of which returned to normal levels with the topical treatment. Furthermore, tocotrienol significantly decreased malondialdehyde, a lipid peroxidation end product found to be high in cataracts, and restored the lens soluble to insoluble protein ratio to normal levels.
And finally, it has positive influence on the immune system. One study showed that annatto tocotrienol combined with antibiotics had the greatest efficacy in decreasing bacteria when compared with tocotrienol or antibiotic treatment alone (Tan, n.d). This may be due to an influence that tocotrienols have on T cells.
Tan, Barrie. The Truth about Vitamin E: The Secret to Thriving with Annatto Tocotrienols . Kindle Edition.
Zinc is a very interesting mineral. It is also one I commonly see low in hair tissue mineral analysis (HTMA).
It plays an important role in facilitating hundreds of biochemical reactions. Due to its role in enzymatic function, it can impact metabolic pathways such as carbohydrate, protein, nucleic acid, and lipid metabolism. It is also a structural component in thousands of transcription factors and can affect gene expression that impacts many physiological processes in the body. “Zinc appears to be part of more enzyme systems than all the rest of the trace minerals combined; over 300 enzymes from every enzyme class (oxidoreductases, hydrolases, lyases, isomerases, transferases, and ligases) require zinc” (Gropper, n.d.). Some of these zinc dependent enzymes include:
- Carbonic anhydrase: acid base balance- found in erythrocytes and renal tubule cells, essential for maintaining acid-base balance/buffering and respiration. The enzyme catalyzes the reaction that allows rapid disposal of carbon dioxide. Activity of this enzyme in red blood cells diminishes with chronic low zinc status in the diet.
- Alkaline phosphatase: Contains four zinc atoms per enzyme molecule, in which two are required for enzyme activity. This enzyme is found in bones and the liver.
- Alcohol dehydrogenase: contains 4 zinc molecules per enzyme molecule, two are required for catalytic activity. This enzyme is important in the NADH-dependent conversion of alcohols to aldehydes. For example, this enzyme converts retinol (form of Vitamin A) to retinal, which is needed for night vision. It also is required for acetyl aldehyde for alcohol metabolism
- Carboxypeptidases A and B and Aminopeptidases- which is involved in protein digestion. These enzymes are secreted by the pancreas into the duodenum. Zinc is bound tightly to carboxypeptidases and is essential for enzymatic activity; in fact, enzyme activity decreases with zinc deficiency (Gropper, n.d.). Aminopeptidases consist of a group of enzymes also involved in protein digestion which contains 1-2 zinc atoms for catalytic activity.
- Delta (Δ)-Aminolevulinic Acid Dehydratase: Heme Synthesis- needed for heme synthesis is zinc dependent. Interestingly, lead when present in the body in high concentrations can replace zinc in the dehydratase and diminishes heme synthesis.
- Superoxide dismutase (SOD1)- an antioxidant found in the cell cytosol requires two atoms of zinc (and two copper) to function. An extracellular form of the enzyme (SOD3) that is also zinc and copper dependent has been characterized and appears to be more sensitive to zinc than is the cytosolic form of the enzyme. Both the cytosolic and extracellular forms of superoxide dismutase serve important antioxidant defense roles in the body by catalyzing the removal of superoxide radicals, O2
- Phospholipase C-this enzyme hydrolyzes the glycerophosphate bond in phospholipids (a structural component of cell membranes!). It requires 3 zinc atoms for catalytic activity.
- Matrix Metalloproteinases-The matrix metalloproteinases are zinc containing endopeptidases (zinc is located in the catalytic site where substrate binds). They generally function in wound healing, degrading components of the extracellular matrix (among other roles) to allow for remodeling of extracellular matrix proteins and tissue repair
- Polymerases, Kinases, Nucleases, Transferases, Phosphorylases, and Transcriptases- Nucleic Acid Synthesis and Cell Replication and Growth Polymerases, kinases, nucleases, transferases, phosphorylases, and transcriptases all require zinc.
- Gene expression- Zinc plays a major structural role in regulating gene transcription by promoting a confirmation change in the shape of the transcription factor protein. You may have heard the term zinc fingers which is often used to indicate the secondary shape (configuration) of the transcription factor proteins when bound to zinc.
In addition to the above roles, zinc helps maintain cell membranes through multiple actions on membrane proteins including direct effects on membrane proteins’ conformation, on protein-to-protein interactions, and on other membrane components
Zinc itself also is believed to stabilize membrane structure by stabilizing phospholipids and thiol (SH) groups in enzymes and membrane proteins that need to be maintained in a reduced state.
Zinc may also stabilize membranes by quenching free radicals as part of metallothionein and by promoting associations between membrane skeletal and cytoskeletal proteins
Additionally, zinc in cells is found bound to tubulin, a protein that makes up the microtubules. Microtubules are thought to act as a framework for structural support of the cell as well as enable movement.
Zinc is also involved with insulin and thus influences carbohydrate metabolism. Zinc is transported into pancreatic b-cells by zinc transporter ZnT8, which also enables uptake into secretory vesicles. Pancreatic b-cells are responsible for insulin production and secretion (Gropper, n.d.).
Zinc can also influence the basal metabolic rate (BMR). A decrease in thyroid hormones and basal metabolic rate has been observed with consumption of a zinc-restricted diet (Gropper, n.d.).
Zinc is also important for taste; it is a component of gustin, a protein involved in taste acuity (Gropper, n.d.).
Cell mediated and humoral immunity are also influenced by zinc. T-cells are critical to immune system function and with zinc deficiency, thymulin activity diminishes and profoundly affects T-cell numbers and functions, and pre-T-cell apoptosis (programmed cell death) (Gropper, n.d.).
Some signs and symptoms of deficiency in adults include anorexia, diarrhea, lethargy, depression, skin rash/ lesions/dermatitis, hypogeusia (blunting of sense of taste), alopecia (some hair loss; remaining hair make take on a reddish hue), vision problems, and impaired immune function, protein synthesis, and wound healing (Gropper, n.d.).
Zinc deficiency can be associated with decreased mobilization of retinol from the liver (even with adequate liver vitamin A stores) as well as decreased plasma retinol-binding protein concentrations (Gropper, n.d.).
An overall deficiency of zinc stores within the body has been implicated in the systemic susceptibility of infection and in the pathogenesis of some cancers (Liu et al., 2011)
Zinc also demonstrates an important role within the lumen of the alimentary canal, as evidenced on the observations that supplementation of oral diets with Zn2+ has beneficial effects on diarrhea and inflammatory conditions of the gastrointestinal tract (Liu et al., 2011). “In gastric mucosa, adequate intracellular stores and luminal content of Zn2+ may regulate integrity of and acid secretion by the gastric glands and enhance protection of the mucosa as a whole against acid-peptic injury (Liu et al., 2011).
Evaluating zinc nutriture is difficult, owing to homeostatic control of body zinc. A variety of indices have been used to assess zinc status, including measurements of zinc in red blood cells, leukocytes, neutrophils, and plasma or serum.
The most common basis for assessment is serum or plasma zinc, with fasting concentrations less than about 70 µg/dL (10 µmol/L) suggesting deficiency. A cutoff of 50 µg/dL, however, may better predict clinical signs of zinc deficiency (Gropper, n.d.). Plasma zinc concentrations range from about 70 to 120 μg/dL (10–18 µmol/L), with plasma containing about 3 mg of zinc. Plasma zinc concentrations decrease after eating, as well as under conditions of infection and trauma
Low fasting plasma zinc concentrations indicate that little zinc is present in the exchangeable zinc pool and may reflect a loss of tissue zinc (especially from the liver). Plasma zinc concentrations, however, must be interpreted with caution because concentrations are influenced by many factors unrelated to zinc depletion, including meals, time of day (diurnal variation), stress, infection, and medications such as steroid therapy. In fact, postprandial (after eating) plasma zinc concentrations have been found to be more sensitive to low dietary zinc intake than fasting plasma zinc concentrations (Gropper, n.d.)..
Metallothionein has also been used to assess zinc status. Concentrations of metallothionein respond to changes in dietary zinc. For example, liver and red blood cell metallothionein concentrations diminish as dietary zinc intake decreases and are thought to reflect zinc status or stores (Gropper, n.d.).
Serum zinc and serum metallothionein concentrations can be used to indicate poor zinc status if both are low. Elevations in serum metallothionein coupled with low serum zinc, however, usually suggest an acute-phase response, and in such conditions these indices are not reliable. Urinary zinc excretion remains fairly constant over a range of intakes and is thought to be a useful marker of status in those with moderate to severe zinc deficiency (Gropper, n.d.)..
Low hair zinc may be associated with chronic intake of dietary zinc in suboptimal amounts; however, the concentration of zinc in hair depends not only on delivery of zinc to the root but also on the rate of hair growth, which is affected by other conditions (including protein status)(Gropper, n.d.).
.Measurement of the activity of zinc-dependent enzymes has also been employed as an index of zinc status. Studies using enzymes as indicators typically have measured carbonic anhydrase or alkaline phosphatase, which “hold” zinc less securely than other zinc metalloenzymes.
Ideally, measurements of activity should be taken before and after zinc supplementation (Gropper, n.d.)..
Supporting deficiency in adults typically requires oral zinc supplementation; doses of 10–20 mg/day are recommended. Although higher doses (often up to 50 mg given two to three times per day) may be prescribed, use of such doses is more likely to impair copper status.
Some population groups—especially older adults, vegetarians, and those with alcoholism and with limited income—have been found to consume less than adequate amounts of zinc.
Alcohol ingestion additionally reduces intestinal zinc absorption and increases urinary zinc excretion.
Additional conditions associated with an increased need for intake include trauma, sickle-cell anemia, and disorders causing malabsorption such as Crohn’s disease, short bowel syndrome, celiac disease, and liver failure, as well as surgical bariatric procedures, especially Roux-en-Y gastric bypass and duodenal switch, used to treat obesity. Diarrhea and intestinal fistulas also substantially increase fecal zinc losses; supplementation with up to 20 mg of zinc/day may be needed under such conditions.
ZINC and COPPER
The detrimental effect of excessive zinc intake on copper absorption is thought to be attributable to zinc’s stimulation of the synthesis of metallothionein, which has a higher affinity for copper than for zinc. With increased intestinal concentrations of metallothionein induced by high zinc levels, ingested copper readily binds to the metallothionein within the enterocyte and becomes “trapped,” preventing its passage into the plasma. The increased risk of copper deficiency precipitated by zinc supplementation led to the Tolerable Upper Intake Level for elemental zinc of 40 mg daily.
Recent reports have begun to explore the mechanisms that regulate cellular homeostasis of Zn2+ in mucosal cells of the gastrointestinal tract (Liu et al., 2011)
There is a relationship to zinc uptake is dependent on intracellular Ca2+ stores.According to Liu et al (2011), baseline conditions, uptake of Zn2+ across the basolateral membrane depends on adequate stores of intracellular calcium ion (Ca2+) . With stimulation by powerful agonists such as forskolin and carbachol, demand for extracellular Zn2+ increases and depends on influx of extracellular Ca2+ .
“In the current set of studies, we find that Ca2+ facilitates optimal uptake of Zn2+ across the cell membrane, implying that it is either a counter-ion in exchange or it is acting as a regulatory second messenger. Membrane proteins that facilitate Zn2+ transport constitute the SLC30A (ZnT) and SLC39A (Zip) gene families” (Liu et al., 2011).
Diminished calcium absorption has been observed with the ingestion of zinc supplements when calcium intake is low (<300 mg/day of calcium). However, calcium absorption appears to be unaffected by zinc when calcium intake is at adequate (recommended) levels.
Cadmium, if present in high concentrations in the body, appears to bind to sites to which zinc would normally bind and thus disrupts normal zinc functions. For example, cadmium can replace zinc in zinc fingers, preventing the fingers from functioning as they would with zinc present.
Zinc is found in foods complexed with nucleic acids and with amino acids that are part of peptides and proteins. The zinc content of foods varies widely.
Very good sources of zinc are red meats (especially organ meats) and seafood (especially oysters and mollusks). Other relatively good animal sources of zinc include poultry, pork, and dairy products. Animal products are thought to provide 40–70% of zinc consumed by most people in the United States.
Whole grains and legumes also provide moderate amounts of zinc.
Cereals, some of which may be fortified, are thought to provide about 30% of the zinc in the U.S. diet. Fruits contain little zinc.
Plant sources, however, not only have lower zinc contents, but zinc from plants is also absorbed to a lesser extent than zinc from animal sources (e.g., meat).
Zinc absorption is enhanced with:
Ligands or chelators including organic acids (like citric acid and picolinic acid) and prostaglandins may bind and promote zinc absorption
Glutathione and products of protein digestion, such as amino acids, serve as ligands (such as sulfur, cysteine, or nitrogen). Interestingly, amino acids serving as ligands help maintain zinc’s solubility in the gastrointestinal tract
Absorption of zinc is also enhanced by an acidic environment. Thus, the use of medication such as antacids, H2 receptor blockers (such as Zantac [ranitidine], Tagamet [cimetidine], or Pepcid [famotidine]), and proton pump blockers (such as Prevacid [lansoprazole] or Prilosec [omeprazole]), which are commonly taken to treat heartburn, gastroesophageal reflux disease, and ulcers, increases gastric and proximal intestinal pH and decreases zinc absorption
Phytic acid found in plant foods, particularly legumes, lentils, nuts, seeds, and whole-grain cereals decrease absorption
Other minerals such as iron and calcium negatively impact absorption
Gropper, Sareen S.; Smith, Jack L.; Carr, Timothy P.. Advanced Nutrition and Human Metabolism (Page 509). Wadsworth Publishing. Kindle Edition.
Liu, J., Kohler, J. E., Blass, A. L., Moncaster, J. A., Mocofanescu, A., Marcus, M. A., . . . Soybel, D. I. (2011). Demand for Zn2+ in acid-secreting gastric mucosa and its requirement for intracellular Ca2+. PLoS ONE, 6(6), e19638. doi:10.1371/journal.pone.0019638
Probiotics can enhance your immune system!
The intestine is considered a key target organ to improve the quality of life in senescence, which can be modulated with a healthy lifestyle with a customized diet including probiotics. Probiotics are demonstrating immunomodulating properties that can alleviate the proinflammatory status of the elderly. “The preservation of gut barrier integrity and an increased ability to fight infections are the main reported immune benefits of probiotics” (Landete et al., 2017). In addition, the intake of a diet rich in phytoestrogens along with the presence of selected probiotic bacteria may lead to the production of equol, enterolignans, and urolithins, which are considered protective against chronic diseases related to aging.
Commensal bacteria can modulate the host inflammatory response, mainly by targeting NF- 𝜅B. According to Landete et.al, an aged-type microbiota shows low microbial biodiversity, enriched in pathobionts and facultative anaerobes and depleted of Firmicutes, which is linked with an increase of proinflammatory signals. Improving the profile of the gut microbiota through lifestyle and nutritional modifications may exert beneficial immunological effects. They can preserve the gut barrier integrity and function and regulate expression of tight junctions. “Probiotic treatments can ameliorate some of these processes modulating cytokine production, improving distribution and function of NK cells, macrophages, granulocytes, and T cells in the circulation, and enhancing mucosal and systemic antibody responses” (Landete et al., 2017). The presence of some beneficial microorganisms can also help the production of bioactive metabolites as equol, enterolignans, and urolithins. A diet rich in isoflavones, lignins from flaxseeds, or eggagitannisn from cherries/pomegranates would thus work synergistically with probiotics to activate these bioactive metabolites.
Below is a chart that summarizes some probiotics and how they influence immunity
Here is a screenshot of some important resources for probiotics and prebiotics (food for probiotics).
I love these muffins ! Not only are they low in sugar and contain healthy fat, they are also high in protein, low in oxalate and may be helpful in a healthy detox program. I keep them in the fridge and grab one or two when I am crunched for time and need a quick snack. These are great breakfast foods.