Biology of amino acids influences multiple cellular networks important for metabolic and energy system, and these and other metabolites play fundamental roles in many diseases. PD candidates are developed as consumer health products that maintain metabolic health in the following program areas:


Although life expectancy at age 60 is undoubtedly increased in high-income countries, elderly subjects spend several years in prolonged disability. Among the multiple chronic disorders possibly leading to disability, the geriatric syndrome of frailty is a significant public health priority.

It is a highly problematic state of vulnerability characterised by decreased reserve and diminished resistance to stressors (Clegg et al., 2013) (Rodríguez-Mañas, 2013). While early detection and prevention of frailty are crucial in this scenario, unfortunately no healthcare programmes or pharmacological treatments are available for frail older people. Increasing evidence recognises sarcopenia, a state of age-related quantitative muscle loss (Cruz-Jentoft – Zamboni 2010) as the central biological substrate of frailty (Landi F, 2015). The prevalence of sarcopenia increases with age and has been estimated in the order of 5 to 13% in the 60-70-year-old population, rising up to 50% among subjects aged 80 years or older (Janssen, 2011). Reduced relative muscle mass is significantly and independently associated with disability in older subjects (Landi F, 2015).

A sarcopenia-linked global health challenge in the elderly population is the obesity epidemics. Intramyocellular lipid accumulation and/or intermuscular adipocyte formation occur in muscle of obese patients, contributing to functional impairment. In this scenario, the hypothesis is emerging that lean mass loss, together with muscle fat accumulation and metabolic derangement, with or without the presence of obesity, are at the core of the functional defects of the elderly frail population (Buch, 2016).

While the complex, interlinked causal mechanisms are far from being established, age-dependent decrements in mitochondrial function play a key role in the frail phenotype (Buch, 2016). Indeed, mitochondrial dysfunction (e.g., changes in mitochondrial biogenesis and dynamics, reduced mithocondrial hormesis, and impaired crosstalk among mitochondria and other cellular organelles) take part to the energetics decline of the elderly (Nisoli & Valerio, 2014; Valerio & Nisoli, 2015). Thus, a critical necessity in sarcopenic elderly people is developing products able to promote both mitochondrial boosters and anti-obesity programs. PD candidates are being developed to answer these health requests.



Fatty liver disease is a pathological condition characterized by the accumulation of large lipid droplets in hepatocytes via the process of steatosis, with consequent dysfunction in energy metabolism1. Above all, non-alcoholic fatty liver disease (NAFLD) is becoming global health problems in adults as well as in children, mainly linked to increase in obesity with or without insulin resistance2,3.

The clinical implications of NAFLD, which accounts for 75% of all chronic liver diseases, mainly derive from its high incidence and risk of evolving in cirrhosis, liver failure, and hepatic cancer. Currently, NAFLD is considered the most widespread hepatic alteration in industrialized countries (25-45%), and is continuously and rapidly increasing4,5. At the cellular level, important mitochondrial dysfunctions and bioenergetic defects are the hallmark of the disease.

In particular, an overproduction of radical oxygen species (ROS) and defects in mitochondrial respiration6, mtDNA damage7, changes of the mitochondrial protein profiles7, impairment of mitophagy with consequent accumulation of damaged mitochondria are observed in hepatic cells in vivo6. To date, no effective therapeutic approach for the treatment of NAFLD has been approved.

Based on the ability of specific amino acid mixtures to increase mitochondrial mass and function in different cell types, including hepatocytes, investigations have been performed both in vitro and in vivo. The PD design platform has identified new amino acid formulas to ameliorate mitochondrial dysfunction in liver disease models.


  1. Reddy JK, Rao MS. Lipid metabolism and liver inflammation. II. Fatty liver disease and fatty acid oxidation. Am J Physiol Gastrointest Liver Physiol. 2006 May;290(5):G852-8.
  2. Browning JD, Szczepaniak LS, et al. Prevalence of hepatic steatosis in an urban population in the United States: impact of ethnicity. Hepatology 40: 1387–1395, 2004.
  3. Evans RM, Barish GD, and Wang YX. PPARs and the complex journey to obesity. Nat Med 10: 1–7, 2004
  4. Nobili V, Alkhouri N, Alisi A et al., Nonalcoholic fatty liver diseases. A challenge for pediatrician. JAMA Pediatr 2015; 169:170-6
  5. Rinella ME. Nonalcoholic fatty liver diseases. A systematic review JAMA 2015; 313:2263-73
  6. Wang L, Liu X, Nie J et al. ALCAT 1 controls mitochondrial etiology of fatty liver diseases linking defective mitophagy to steatosis. Hepatology 61:486-96, 2015
  7. Paradies G, Paradies V, et al. Oxidative stress, cardiolipin and mitochondrial dysfunction in nonalcoholic fatty liver disease. World J Gastroenterol. 2014 Oct 21; 20(39): 14205–14218.


  1. Bolasco P, Caria S, Cupisti A, Secci R, Saverio Dioguardi F. A novel amino acids oral supplementation in hemodialysis patients: a pilot study. Ren Fail. 2011;33(1):1-5.
  2. Cupisti A, Bolasco P. Keto-analogues and essential aminoacids and other supplements in the conservative management of chronic kidney disease. Panminerva Med. 2017 Jun;59(2):149-156. doi: 10.23736/S0031-0808.16.03288-2.
  3. Murtas S, Aquilani R, Deiana ML, Iadarola P, Secci R, Cadeddu M, Salis S, Serpi D, Bolasco P. Differences in Amino Acid Loss Between High-Efficiency Hemodialysis and Postdilution and Predilution Hemodiafiltration Using High Convection Volume Exchange-A New Metabolic Scenario? A Pilot Study. J Ren Nutr. 2019 Mar;29(2):126-135. doi: 10.1053/j.jrn.2018.07.005.

Central Nervous System

Central nervous system (CNS) comprises the brain, coordinating higher-level functions, and the spinal cord serving mainly as the communication pathway between the brain and the periphery. Disabilities from central nervous system’s injuries are a function of the mode, severity, and anatomical location of the insult.

Regardless of the initial location of the insult to the CNS, injury is an ongoing process, with primary damage leading to a cascade of deleterious events that can affect both cell body and axonal function, resulting in continued dysfunction and prolonged degeneration. Traumatic brain injury (TBI) and traumatic spinal cord injury (SCI) occur when an external physical insult causes damage and can range from mild to severe. Spinal cord injury is cause of disability with devastating neurological outcomes and limited therapeutic opportunities.

There are two major types of spinal cord injury, transaction of the spinal cord and spinal cord contusion (SCI). SCI results in partial or complete loss of motor or sensory functions below the level of the injury, with devastating consequences for the patient, both at the physical and psychological level. The pathological basis underling the diseases is the loss of neural tissue that disconnects the neuronal impulses from the CNS to the muscles. Worldwide approximately 250,000-500,000 people suffer an injury to the spinal cord every year, corresponding to 30-60 people every hour.

These patients require extensive medical assistance throughout their life, with an estimated lifetime cost of 1-4 million € per patient. Although SCI represents a very relevant social and economic burden, few new therapeutic options are available. In the last 30 years, progress in medical assistance has increased the survival rate of SCI patients. Basic and translational research, however, did not succeed in substantial improving the neurological manifestations.

Based on the ability of specific amino acid mixtures to promote mitochondrial mass and function in neurons, in addition to synaptic number and function, PD design platform has identified new amino acid formulas to ameliorate SCI symptoms in murine models.

Mitochondrial Diseases

Mitochondrial diseases (MDs) are genetic disorders characterized by defects in oxidative phosphorylation (OXPHOS), the final pathway of aerobic metabolism. Although heterogeneous, MDs are mainly characterized by a significant reduction in ATP production, which has deleterious effects in organs with high energy demand, such as brain and skeletal muscle.

Over the past three decades, a number of mitochondrial DNA (mtDNA) mutations that cause human disease have been identified. These are associated with a broad spectrum of clinical manifestations, including blindness, deafness, dementia, movement disorders, weakness, cardiac failure, diabetes, renal dysfunction, and liver disease. The molecular and biochemical characterization of mtDNA diseases has provided new insights into the nature of human degenerative diseases. No efficient therapies exist for these diseases.

It was demonstrated that targeting mitochondrial biogenesis is effective in ameliorating the clinical manifestations and the OXPHOS deficiency in animal models; however, the reported side effects strongly limit the use of the proposed drugs in humans.

PD design platform has identified new amino acid formulas to stimulate mitochondrial biogenesis in fibroblasts of patients affected by different mitochondrial diseases.