US
The rebalance
of physiological
fertility
MULTICENTRIC STUDY
REPRODUCTION
FEMALE
In dogs and cats, as in humans, symptoms related to adverse reactions to food are very common and can affect various parts of the body, including the gastrointestinal system, skin, ears, eyes, nervous system, urinary system, respiratory system and reproductive system.
Although skin and intestinal problems are the most common symptoms, there has been an increase in disorders associated with food intolerances that affect different parts of the body, like the reproductive system. These diseases often do not respond to pharmacological treatment and recur frequently, causing suffering to the animal and frustration for the owner. In these cases, a special diet offers an essential tool to limit and avoid the indiscriminate use of drugs.
Based on these considerations, the FORZA10 Research and Development Center set the objective of developing the concept of physiological rebalancing through food, creating a line of Nutraceutical products for specific organs or systems. “Nutraceutical” originates from the combination of the words nutrition and pharmaceutical. Nutraceutics is a new branch of medicine that studies the effects of specific natural substances that are added to food with the purpose of preventing or treating a variety of disorders. This discipline connects natural and pharmacological medicines. Nutraceutical foods also provide a simple and definitive solution to the problem of administering drugs via topical, oral and/or parenteral routes.
INTRODUCTION
MATERIALS AND METHODS
The purpose of this study is to evaluate the effectiveness of a special diet designed to improve reproductive parameters in female dogs, either with or without a history of reproductive problems. The efficacy of the diet was tested through a dietary trial of variable duration (depending on the onset of heat and subsequent pregnancy), measuring parameters relating to reproductive efficiency.
This multicentric clinical study is based on standardized protocols used by veterinary professionals operating in the field of canine reproduction.
AIM OF THE STUDY
The FORZA10 R&D Center, with a collaboration of Italian veterinarians who specialize in canine reproduction, ran a study in 2012 and the early months of 2013. The test subjects were 48 female dogs belonging to 19 different breeds and ranging in age from 1 to 8 years, 46 of which had one or more of the following reproductive problems:
• Irregular cycle with prolonged anoestrus;
• Primary anoestrus;
• Irregular or silent heats;
• Infertility, subfertility, small litter size for the breed.
Two subjects that had no clinical history of reproductive problems were included in the study to test whether the diet could induce heat.
The subjects underwent a thorough check-up, collecting anamnestic data, particularly reproductive data, from the owner.
When reproductive problems were reported when taking the case history, deep samples were taken with a sleeved swab to test for vaginal mycoplasma and ureaplasma. Nine of the subjects tested positive with a pathogen load of > 10,000 UFC/ml. These dogs
were given antibiotic therapy specific for the pathogen identified.
The subjects included in the study began the FORZA10 Reproduction Female diet following initial examination and after completion of any antibiotic treatment.
Data on the following topics was recorded from the beginning of the diet:
• Length of the treatment before return of heat;
• Mating;
• Pregnancy;
Of the 42 dogs that went into heat, 31 were mated (73.8%) and 29 of these became pregnant (93.5%). The percentage success rate in this case was therefore also very high.
These dogs gave birth to litters that ranged from 4 to 12 puppies, with an average of 7.4 puppies/mother. The test group contained 8 subjects with a clinical history of infertility or subfertility. Of these dogs, 7 went into heat normally after beginning the diet. All of these dogs were mated and 5 became pregnant, giving a success rate of 71.4%. These dogs gave birth to litters that ranged from 7 to 12 puppies, with an average of 8.6 puppies/mother - a respectable number, especially considering the history of these subjects.
Information regarding the previous litter was available for 4 of the dogs that gave birth. Comparison of the data for these 4 dogs shows a 60.9% increase in the number of puppies born, with a current average of 9.3 puppies/ mother, compared to a previous average of 5.8 puppies/ mother.
Referring to the whole group of 48 subjects, it is interesting to note that the 5 subjects diagnosed with primary anoestrus all went into heat in an average of 17.8 days (with a high variability in this figure that is probably due to the small sample size). Although the sample size is too limited for this data to be statistically valid, the result is worth mentioning and will be better defined in future studies.
With respect to the 2 subjects that were included to attempt to induce heat, both dogs went into heat 9 or 10 days after beginning the diet, approximately 20 days earlier than heat was expected.
In addition, one case in particular is worth mentioning - a 7 year old Bernese Mountain Dog in which heat was induced. After inducing heat, the dog became pregnant and gave birth to 9 puppies, an increase of 125% compared to the previous litter of 4. While this data is not significant in and of itself, the positive trend with respect to the previous litter size makes this promising result worth noting so that it can be compared with data from any future studies involving the product FORZA10 Reproduction Female. HEAT
YES
YES YES
MATING PREGNANCY
NUMBER OF PUPPIES on 29 animals
MEDIUM/LARGE BREEDS SMALL BREEDS
AVERAGE NUMBER OF NEONATES GREA T D ANE BERNESE MOUNT AIN DOG CA UC ASIAN SHEPHERD DOG GERM AN SHEPHERD ENGLISH SE TTER
42 of the 48 subjects (87.5%) went into heat after beginning the FORZA10 Reproduction Female diet in a timeframe
that ranged from 5 to 64 days, with an average of 24.3 days. This is a very encouraging result, since only 6 out of 48 subjects did not go into heat within 5 weeks of starting the diet.
The encouraging data seems to support the hypothesis that a proper balanced diet that uses raw materials that are free of harmful substances and contaminants (especially residues of antibiotics like tetracycline that are found in meat produced by intensive farming), is the basis for restoring the physiological state, particularly the reproductive system, of the subjects.
The results of this preliminary study, which is part of a larger project in the field of reproduction, provide a starting point for further investigation of the mechanisms involved.
The FORZA10 R&D Center is aware of the limitations of this work and is planning additional in-depth clinical studies to determine the real effects of the diet on the reproductive system, with possible inclusion of a control group and expansion of the test group size.
The aim of such research would be to analyze systematically many of the factors that influence the hormonal systems, as well as the functionality of the organs involved. This could be used to better explain, for example, the significant variability in the manifestation of pro-oestrus signs after starting the diet.
It is our belief that, as has been clearly demonstrated in FORZA10 studies focusing on other organs and systems of the body, the inhibition of reproductive function may be due to a state of chronic inflammation caused by the presence of residues of oxytetracycline in the body, which are ingested by eating ordinary commercial food.
This inflammatory state interferes with normal physiological mechanisms on various levels, altering the hormonal axes and/or causing anatomical lesions. This provides a plausible explanation for the results of the present study and their variability. A proper diet that contains no contaminants would permit the anatomical damage caused by the chronic inflammation to heal over a medium to medium-long timeframe (explaining why some of the dogs went into heat more than a month after beginning the diet). Unblocking the physiological hormonal mechanisms allowed the “anatomically healthy” subjects that had experienced silent heats or prolonged anoestrus to display clear signs of pro-oestrus even shortly after changing foods, with activation of the hypothalamic-pituitary-ovary axis in as little as 3 days.
CONCLUSIONS
Preliminarily, it seems that the FORZA10 Reproduction Female diet has a real and pronounced stimulatory effect on the reproductive cycle of female dogs and has beneficial effects on different phases of reproduction. This product is intended to become an essential support for dog breeders, improving and sustaining the performance of brood dogs. This would provide benefits for the breeder as well as the dog, contributing to the animal achieving an optimum state of health and wellbeing.
In the past ten years, there has been a notable decrease in male and female fertility in both humans and dogs. In dogs, the phenomenon has occurred over such a short period of time and wide area that people involved in dog breeding have been holding meetings, debates and round table discussions on the topic, thus revealing the true dimensions of the problem. The connection between food and fertility has been recognized for some time in both farm animals and companion animals. Gestation and lactation are clearly critical phases of reproductive activity, including from the perspective of energy needs since additional energy is required for fetal growth and milk production. Problems that compromise the reproductive efficiency of the brood dog, such as episodes of delayed heat, silent heat, irregularities in the oestrous cycle, reduced litter size and low vitality of the puppies are increasingly common.
Nutrition plays a key role since poor nutrition not only compromises the health of the animal but also affects its reproductive success and the growth of its puppies. In fact, a proper diet, both from a quantitative and qualitative perspective, can have an impact on fertility, the manifestation of heat, embryo survival, litter size, birth weight, lactation and neonatal vitality.
The FORZA10Reproduction Female formula, the subject of this study, is a product that was specifically designed and formulated by FORZA10as a nutritional tool to support efficient functioning of the reproductive system in female dogs. This two-component food should be given to female dogs in the period preceding reproduction. The product is composed of kibbles that are rich in fish (the only protein source) and fish oil, which is naturally rich in Omega3. The essential fatty acids, Omega3 in particular but also Omega6, are important in maintaining cell health and have significant beneficial properties for the entire body. It is therefore understandable that a diet deficient in these substances may cause disorders of the skin, nervous system, immune system, respiratory system, kidney function and the reproductive
system. The heart-shaped tablets contain an exclusive blend of natural substances that contribute to the improvement of sexual and reproductive health:
• Maca. Also known as “ginseng of the Andes”, this root belongs to the brassicaceae family. It has been cultivated since the time of the Incas for its energy-giving properties and high nutritional density, being rich in protein, unsaturated fatty acids and minerals. Spanish colonists exported maca to Europe, where it quickly gained popularity due to its stimulating effects on energy level, libido and fertility. Maca does not act on particular systems but rather has beneficial effects throughout the body. In fact, its beneficial properties range from improved athletic performance to immunostimulatory effects. In addition, it regulates the balance of the various systems of the body. However, since it was first cultivated, maca has primarily been known for its pronounced effect on fertility and its aphrodisiacal properties. In women, therapies based on this plant are used to treat many symptoms of menstrual disturbances and menopause and to restore hormonal balance.
• Carotenoids. These substances have been added to the formula due to the numerous direct and indirect beneficial effects that they have on reproductive activity. In addition to being potent antioxidants, they inhibit mutation, increase immune response and reduce the incidence of light-induced neoplasms. They also contribute to improving the uterine environment and increasing the production of progesterone by luteal cells thanks to their high antioxidant capacity, which is most evident in tissues that have a low partial pressure of oxygen.
• Folatesand folic acid. With respect to reproduction, these substances are connected with healthy fetal development and growth. Deficiencies or changes in folate metabolism can cause deformities in puppies, including cleft palate, neural tube defects and heart defects. In many cases, these defects bring about the death of the puppy during the perinatal period. Such deformities can also increase the risk of dystocia, particularly in toy and miniature breeds. • Vitamin E. This potent natural antioxidant contributes to
the proper functioning of essential hormonal systems, including the hypothalamic-pituitary-adrenal axis and the hypothalamic-pituitary-gonadal axis. A deficiency of this vitamin in pregnant females can cause the death and resorption of the fetus.
• Zinc. This ubiquitous element is found in more than 2,000 enzymes involved in digestion and metabolism, some of which play a fundamental role in detoxification, bone marrow, protein digestion, RNA synthesis, and aerobic and anaerobic energy production. A zinc deficiency can cause stunted growth and cognitive retardation, absent or delayed puberty and increased susceptibility to diseases. In females, zinc deficiencies can lead to changes in the oestrous cycle, subfertility, spontaneous abortions, premature births, and an increase in dystocia caused by fetal deformities.
1. Agarwal A, Gupta S, Sharma RK, Role of oxidative stress in female reproduction, Review Reproductive Biology And Endocrinology.
2. Andrews JC, Nolan JP, Hammerstedt RH, Bavister BD, Role of zinc during hamster sperm capacitation, Biology Of Reproduction 51, 1238-1247 (1994).
3. Case LP, Carey DP, Hirakawa DA, Daristotle L, Canine and feline nutrition, 2nd Ed, Ed. Mosby 1995.
4. Concannon PW, Hansel W, Visek WJ, The ovarian cycle of the bitch: plasma estrogen, LH and progesterone, Biol Reprod, vol.13 (1), pag.112-121, 1975. 5. Eilts BE, Davidson AP, Approach to infertility in the dog and bitch., in
Proceedings of the American Animal Hospital Association Annual Meeting, 2005.
6. Fontbonne A, Infectious reproductive problems in kennels, in Proceedings of 5th Biannual Congress, European Veterinary Society for Small Animal Reproduction (EVSSAR), Budapest, Hungary, 2006
7. Fontbonne A, Infertility in bitches and queen: recent advances, Rev Bras Reprod Anim, Belo Horizonte, vol.35 (2), pag. 202-209, 2011
8. Grandjean D, Paragon BM, Rationnement alimentaire et prévention chez le chien 1, Le Point Vétérinaire, vol.18, pag.519-524, 1986 IN: Hand N.S., Thatcher C.D., Remillard R.L., Roudebush P., Novotnt B. J. (eds): Small Animal Clinical Nutrition, 5th Ed, Mark Morris Institute, 2010.
9. Grandjean D, Pierson P, Cacciani F, Pawlowiez S, Michallet T, Morchi F, Massoni G, Guida pratica dell’allevamento canino, Aniwa Publishing, Royal Canin, 2003.
10. Hathcock J, Vitamin, beta carotene and mineral safety, Journal Of Orthomolecular Medicine Vol. 10. 2nd Edition.
11. Kaunitz H, Slanetz CA, Johnson RE, Babayan VK, Barsky G, Nutritional properties of the triglycerides of saturated fatty acids of medium chain-length, 48th Annual Meeting, American Oil Chemists’ Society, April 28 To May 1, 1957, New Orleans, LA.
12. Matte Jj, Girard Cl, Brisson Gj, Folic acid and reproductive performances of sows. Journal Of Animal Science [1984, 59(4):1020-1025] (Pmid:6542561). 13. Scott JM Folate and vitamin B12. Proc Nutr Soc 58 (2): 441-8. Pmid 10466189
May 1999.
14. Walter B, Otzdorff C, Brugger N, Braun J, Estrus induction in Beagle bitches with the GnRH-agonist implant containing 4.7 mg Deslorelin, Theriogenology 2011 Apr 1;75(6):1125-9. doi: 10.1016/j.theriogenology.2010.11.022. Epub 2011 Jan 8.
15. Zingg JM, Azzi A, Non-antioxidant activities of vitamin E, Curr Med Chem. 2004 may; 11(9):1113-33. Review.
REFERENCES
FELINE FORMUL
CANINE FORMULA
Active Fresh System
International patents pending
European patent n. EP 2526781