Exterior Postdoctoral Analysis Staff, Biology Unit, School of Human Sciences, College of Thessaly, 38221 Volos, Greece
Summary
1. Introduction
Protein is a necessary macronutrient wanted by the human physique for development and upkeep. Meals wealthy in animal protein are meat, fish, eggs, poultry, and dairy merchandise, whereas plant meals excessive in protein are primarily legumes, nuts, and grains. The present beneficial dietary allowance (RDA) for protein is 0.8 g protein/kg physique weight/day for adults (for youngsters 1.5 g protein/kg physique weight/day, and for adolescents 1.0 g protein/kg physique weight/day) [1]. Nevertheless, excessive protein diets (outlined as an consumption above the present RDA) are promoted intensively by the dietary dietary supplements business and they’re thought-about to be “the gold standard” by many athletes (particularly bodybuilders) for muscle improvement and/or physique fats loss. Then again, a number of scientists declare that the overuse of protein dietary supplements or excessive dietary protein consumption might trigger problems to human well being [1–7]. The purpose of this evaluate examine is to find out the potential well being risks attributable to excessive protein/excessive meat consumption obtained from eating regimen or dietary dietary supplements primarily based on the human research existent within the literature. Through the interval of October 2012–Might 2013, a search was carried out within the databases PubMed (1967 to current) and Google Scholar (1966 to current). There have been included research in English language which had analyzed the potential well being risks attributable to long-term excessive protein consumption obtained from eating regimen or dietary dietary supplements in people. The titles and the abstracts of the preliminary research recognized have been searched with a purpose to decide in the event that they fulfill the choice standards. The integral textual content of chosen titles was extracted and the reference checklist of chosen articles was consulted with a purpose to discover out different related publications. 32 research (21 experimental human research and 11 critiques) have been recognized which comprised knowledge associated to the potential opposed results of protein overconsumption utilizing the next search phrases: “high protein diet,” “protein overconsumption,” “protein overuse,” and “high meat diet.” The experimental human research’ options included within the examine are conveyed in Desk 1 (critiques will not be included).
2. Problems of Bone and Calcium Homeostasis
Weight loss plan which is excessive in protein generates a considerable amount of acid in physique fluids [2]. The kidneys reply to this dietary acid problem with internet acid excretion, and, concurrently, the skeleton provides buffer by energetic resorption of bone leading to extreme calcium loss [2]. Furthermore, acid loading instantly inhibits renal calcium reabsorption resulting in hypercalciuria together with the exorbitant bone loss [3, 4]. In a metabolic examine a rise in protein consumption from about 47 to 112 g triggered a rise in urinary calcium and a lower in calcium retention. The info indicated that protein-induced hypercalciuria was attributable to an elevation in glomerular filtration fee and a decrease fractional renal tubular reabsorption of calcium, the latter of which brought on by the elevated acid load on the renal tubular cells [8]. One other examine on topics consuming diets containing 48 g protein every day to 142 g confirmed that urinary calcium doubled, whereas the calcium stability grew to become unfavorable [9]. As well as, the impact of dietary protein on markers of bone turnover has been evaluated [10]. On this examine the topics have been on a well-balanced eating regimen for two weeks which was adopted by 4 days of an experimental eating regimen containing one in all three ranges of protein (low, medium, or excessive). Urinary calcium excretion was considerably greater, and urinary N-telopeptide excretion (indicator of bone resorption) was considerably better in the course of the excessive protein than in the course of the low protein consumption. Knowledge urged that, at excessive ranges of dietary protein, at the least a portion of the rise in urinary calcium mirrored elevated bone resorption [10]. Moreover, topics on a low-carbohydrate high-protein (LCHP) eating regimen for six weeks had elevated urinary calcium ranges, decreased calcium stability, and decreased serum osteocalcin concentrations [11]. In a potential examine, protein was related to an elevated threat of forearm fracture for girls who consumed greater than 95 g per day in contrast with those that consumed lower than 68 g per day. Girls who consumed 5 or extra servings of purple meat per week additionally had a considerably elevated threat of forearm fracture in contrast with girls who ate purple meat lower than as soon as per week [12]. Moreover, the impact of high-protein diets on the excretion of calcium in urine was evaluated in regular individuals and sufferers with nephrolithiasis. All topics got diets containing 0.5 g protein/kg/day, whereas, in the course of the experimental part, every particular person obtained an extra 1.5 g protein/kg/day. There was a constant improve in urinary calcium with the high-protein eating regimen averaging 88% above management within the normals and 82% within the sufferers [13]. Furthermore, in a examine the place protein consumption was different from 47 g/day (low protein eating regimen) to 95 g/day (medium protein eating regimen) and to 142 g/day (excessive protein eating regimen) the urinary calcium elevated considerably with every improve in protein (168, 240, and 301 mg, resp.) [14]. As well as, it has been proven that growing the protein consumption from 48 to 141 g every day triggered a extremely vital elevation in urinary calcium, the imply every day values being 175 and 338 mg, respectively [15]. In one other examine the connection of animal protein wealthy eating regimen to calcium metabolism was investigated throughout a 12-day dietary interval. A rise in urinary calcium excretion was discovered indicating that the animal protein-induced calciuric response might be a threat issue for the event of osteoporosis [16]. Notably, it has been proven that the consumption of excessive calcium diets is unlikely to stop the unfavorable calcium stability and possible bone loss induced by the consumption of excessive protein diets (protein-induced hypercalciuria) [17]. On this experiment (a 95-day metabolic examine) topics obtained method diets supplying 12 g nitrogen or 36 g nitrogen, and roughly 1400 mg calcium per day. Total calcium stability was −37 mg/day on the 12 g nitrogen eating regimen, and considerably decrease at −137 mg/day in topics consuming the excessive protein eating regimen [17]. Moreover, dietary extra (2 g/kg/day) in animal protein for 1 week led to vital modifications in urinary calcium excretion charges [18]. Moreover, in an fascinating examine the results on urinary calcium ranges of accelerating dietary protein from 50 to 150 g protein have been in contrast with these of accelerating the sulfur amino acids to simulate the quantities current within the 150 g protein eating regimen. The rise in protein consumption triggered urinary calcium to double, whereas sulfur amino acids added to the low protein eating regimen additionally triggered urinary calcium to extend [19]. Furthermore, a potential cohort examine confirmed {that a} excessive ratio of dietary animal to vegetable protein will increase the speed of bone loss and the chance of fracture in postmenopausal girls. Animal meals present predominantly acid precursors, whereas protein in vegetable meals is accompanied by base precursors not present in animal meals. Imbalance between dietary acid and base precursors results in a persistent internet dietary acid load which will have opposed penalties on bone. A rise in vegetable protein consumption and a lower in animal protein consumption might lower bone loss and the chance of hip fracture [20].
3. Problems of Renal Perform
Low fluid consumption and extreme consumption of protein are necessary threat components for kidney stones [3]. Protein ingestion will increase renal acid excretion, and acid masses, in flip, could also be buffered partially by bone, which releases calcium to be excreted by the kidney. This protein-induced hypercalciuria might result in the formation of calcium kidney stones [4]. Moreover, animal protein can also be the main dietary supply of purines, the precursors of uric acid. Extreme consumption of animal protein is subsequently related to hyperuricosuria, a situation current in some uric acid stone formers [5]. Uric acid solubility is basically decided by the urinary pH. Because the pH falls under 5.5 to six.0, the solubility of uric acid decreases, and uric acid precipitates, even when hyperuricosuria is just not current [5]. The pathobiochemical mechanisms of animal protein-induced nephrolithiasis are proven in Determine 1. An fascinating examine on the results of protein overload on stone-forming propensity confirmed that consumption of high-protein eating regimen for six weeks delivers a marked acid load to the kidney and will increase the chance for stone formation (urinary citrate ranges decreased, and urinary saturation of undissociated uric acid elevated) [11]. Moreover, in a examine of three 12-day dietary intervals throughout which the eating regimen of the topics contained vegetable protein, vegetable and egg protein, or animal protein, it was discovered that the animal protein-rich eating regimen was related to the very best excretion of undissociated uric acid as a result of discount in urinary pH [16]. Furthermore, citrate excretion was diminished due to the acid load, and urinary crystallization research revealed that the animal protein eating regimen conferred an elevated threat for uric acid stones [16]. In one other examine it was proven {that a} excessive protein consumption induced modifications in urinary uric acid and citrate excretion charges and a lower within the potential of urines to inhibit calcium oxalate monohydrate crystal agglomeration [18]. The decreased potential of urines to inhibit the agglomeration of calcium oxalate crystals might present a attainable physicochemical clarification for the opposed results of high-protein eating regimen on renal stone formation [18]. Moreover, it has been indicated that high-protein consumption might trigger elevated glomerular filtration fee and decreased fractional renal tubular reabsorption of calcium and urinary sodium [19]. In one other examine, wholesome topics with a historical past of renal stones ate up a low (LPD) and a excessive (HPD) animal protein eating regimen; after 2 weeks it was discovered that top dietary consumption of purine-rich animal protein had an affect on urinary urate excretion and supersaturation in renal stone illness [21]. There was a rise in urinary urate, urinary acid excretion, ammonium ion excretion, and uric acid supersaturation and a fall in urine pH on HPD. The danger of forming uric acid or ammonium urate crystals or stones within the urine was elevated on a excessive protein eating regimen [21]. Furthermore, in a potential cohort examine it was investigated whether or not protein consumption influences the speed of renal perform change over an 11-year interval. The outcomes confirmed that top complete protein consumption, significantly excessive consumption of nondairy animal protein, might speed up renal perform decline in girls with delicate renal insufficiency [22]. Moreover, a examine in regards to the short-term impact of accelerating the dietary consumption of animal protein on the urinary threat components for stone-formation confirmed elevated ranges of urinary calcium and oxalate. The accompanying improve in dietary purine triggered a rise within the excretion of uric acid. The general relative likelihood of forming stones, calculated from a mix of the chance components, was markedly elevated (250%) all through the interval of excessive animal protein ingestion [23].
4. Elevated Most cancers Threat, Problems of Liver Perform, and Precipitated Development of Coronary Artery Illness – “protein toxicity symptoms”
As much as 80% of breast, bowel, and prostate cancers are attributed to dietary practices, and worldwide comparisons present optimistic associations with excessive meat eating regimen [6]. The affiliation, nevertheless, appears to have been extra constantly discovered for purple meat or processed meat and colorectal most cancers [7]. Attainable mechanisms embrace the formation of heterocyclic amines in meat when it’s cooked. These heterocyclic amines require acetylation by P450 enzymes, and people with the fast-acetylating genotype who eat excessive quantities of meat could also be at elevated threat of large-bowel most cancers [6]. It ought to be observed that purple meat is the principle dietary supply of saturated fats, which has been related to breast and colorectal cancers [1]. Furthermore, NH3 and N-nitroso compounds (NOC) shaped from residues by micro organism within the giant bowel are in all probability additionally necessary. NH3 is a promotor of large-bowel tumours chemically induced by NOC, and a number of the chromosomal mutations present in human colorectal most cancers are in line with results of NOC and heterocyclic amines [6]. In a cohort examine topics who have been freed from recognized most cancers accomplished a validated meals frequency questionnaire and offered detailed info on different life-style and health-related components. An elevated threat of colon most cancers was related to purple meat consumption [24]. Males who ate beef, pork, or lamb as a fundamental dish 5 or extra occasions per week had an elevated relative threat in comparison with males consuming these meals lower than as soon as per 30 days. The affiliation with purple meat was not confounded appreciably by different dietary components, bodily exercise, physique mass, alcohol consumption, cigarette smoking, or aspirin use [24]. Moreover, in a potential examine topics with no historical past of most cancers, inflammatory bowel illness, or familial polyposis accomplished a dietary questionnaire [25]. After adjustment for complete power consumption, animal fats was positively related to the chance of colon most cancers. The relative threat of colon most cancers in topics who ate beef, pork, or lamb as a fundamental dish every single day was elevated, as in contrast with these reporting consumption lower than as soon as a month [25]. In an fascinating examine the general knowledge set derived from an built-in sequence of case-control research included histologically confirmed neoplasms; controls have been sufferers admitted to hospital for acute, nonneoplastic situations unrelated to long-term modifications in eating regimen [26]. The multivariate odds ratios (ORs) for the very best tertile of purple meat consumption (≥7 occasions/week) in contrast with the bottom (≤3 occasions/week) have been 1.6 for abdomen, 1.9 for colon, 1.7 for rectal, 1.6 for pancreatic, 1.6 for bladder, 1.2 for breast, 1.5 for endometrial, and 1.3 for ovarian cancers. Thus, decreasing purple meat consumption would possibly decrease the chance for a number of frequent neoplasms [26]. Furthermore, highprotein/excessive meat eating regimen might trigger problems of liver perform and precipitated development of coronary artery illness. Hyperalbuminemia and elevated transaminases have been related to high-protein eating regimen [27]. People on excessive protein dietary supplements developed intermittent belly ache, transient elevations in transaminases, and hyperalbuminemia with out there being any identifiable trigger. The signs and abnormalities on the laboratory assessments resolved after the excessive protein consumption was discontinued [27]. In a case-control examine, topics (therapy group/TG) have been studied for 1 12 months by utilizing myocardial perfusion imaging (MPI), echocardiography (ECHO), and serial blood work [28]. MPI and ECHO have been carried out initially and finish of the examine for every particular person. The TG group studied modified their dietary consumption as instructed. Further topics (excessive protein group/HPG) elected a unique dietary routine consisting of a “high-protein” eating regimen [28]. Topics within the TG demonstrated a discount in every of the impartial variables studied with regression in each the extent and severity of coronary artery illness (CAD) as quantitatively measured by MPI. People within the HPG confirmed worsening of their impartial variables. These outcomes would recommend that high-protein diets might precipitate development of CAD by will increase in lipid deposition and inflammatory and coagulation pathways [28].
5. Conclusions
Even if short-term excessive protein eating regimen might be obligatory in a number of pathological situations (malnutrition, sarcopenia, and so forth.), it’s evident that “too much of a good thing” in eating regimen might be ineffective and even dangerous for wholesome people [1, 29]. Many adults and even adolescents (particularly athletes or physique builders) self-prescribe protein dietary supplements and overlook the dangers of utilizing them, primarily attributable to misguided beliefs of their performance-enhancing skills [30]. People who observe these diets are subsequently in danger [31]. Further protein is just not used effectively by the physique and should impose a metabolic burden on the bones, kidneys, and liver. Furthermore, high-protein/high-meat diets might also be related to elevated threat for coronary coronary heart illness attributable to intakes of saturated fats and ldl cholesterol and even most cancers [31]. Tips for eating regimen ought to adhere intently to what has been clinically proved, and by this commonplace there may be presently no foundation to suggest excessive protein/excessive meat consumption above the beneficial dietary allowance for wholesome adults [32–35]. Additional investigation with giant randomized managed research might present extra definitive proof.
References
“protein toxicity symptoms”