WHITE PAPER by Lena Burri, PhD

THE IMPORTANCE OF CHOLINE

Choline is a conditionally essential nutrient,

meaning that it can be produced by the body,

but under certain conditions the supply might be

inadequate [1]. Dogs need choline for the synthesis of

neurotransmitters (i.e. acetylcholine) for memory and

muscle function. Choline is also part of phospholipids

(i.e. phosphatidylcholine), which are important for

transport of lipids, building of cell membranes and

cell membrane signaling [2].

compounds made from choline, transport and pro-

vide methyl groups, which are used by the body to

control protein function and gene expression im-

portant for the proper functioning of the cardiovas-

cular, neurological, reproductive and detoxification

systems.

Moreover, choline has a role in being a methyl

donor. Inasmuch, choline can be processed to

betaine, which then provides a methyl group for the

generation of methionine. Methionine is an essential

amino acid used to build proteins. It is made from

homocysteine, thereby reducing the heart disease

risk, which is associated with homocysteine. These

Many of these pathways are challenged during in-

tense physical activity of long duration, such as dog

sled races, and the demand for free, non-membrane

bound choline is increased to counteract the de-

crease of plasma choline concentrations during

endurance exercise [3, 4]. The exact reasons for why

choline concentrations decline during a high exercise

performance are unclear, but were suggested to not

necessarily reflect choline utilization, instead it might

be a consequence of redistribution of fluid pools

during exertion [5].

Figure 1: Structural function of phosphatidylcholine

Water loving head groups

Micelles Liposome

Bilayer Membrane

CHOLINE

S-adenosyl-homocysteine Phosphatidylethanolamine

PhosphatidylcholineCell membrane & lipid transport component

S-adenosyl-methionineMethyl donor

HomocysteineHeart disease risk factor

Cysteine

Methionine Dimethylglycine

Betaine Choline

AcetylcholineNeurotransmitter

Figure 2: Schematic of the conversion pathwaysof phosphatidylcholine to its metabolites

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Hydrophopic fatty acids: Do not mix with water

Dogs can make choline, but this is not sufficient

to meet all their bodies’ requirements. The rest

needs to be taken up from the diet in either free

or bound form, which reduces the need for methyl

groups supplied by methionine. Particularly dogs

receiving a high-fat diet require extensive lipid

transport by phosphatidylcholine. If an inadequate

amount of choline is made and consumed, liver

choline decreases rapidly [6] and the demand for

methyl groups cannot be met. In dogs, choline defi-

ciency results in liver dysfunction due to liver fat

accumulation [7].

In 2018, a survey of the Association for Pet Obesity

Prevention estimated that 60% of cats and 56% of

dogs in the United States were overweight or obese.

This has serious health consequences including fat

accumulation in the liver. A balanced, healthy diet

for dogs accompanied with regular physical activity

is essential for overall health. In addition, nutritional

supplementation strategies may help to reduce the

risk of weight-related disorders or optimize nutrition

for high-performance dogs. A mean to increase

choline intake in dogs is given in krill meal, which

provides choline in the bound form of phosphatidly-

choline [8, 9].

• Building of cell membranes

• Liver fat transport to prevent fatty liver

• Nerve impulse transmission in brain and muscles

• Providing methyl groups that maintain liver, heart and kidney health

CHOLINE

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CHOLINE ISESSENTIAL FOR:

Because of the methyl group interrelationship, the

requirement for dietary choline supplementation

depends on the availability of methionine, betaine,

folate and vitamin B12. For example, betaine can

replace choline addition, since choline provides the

methyl group for betaine formation. Other factors

that determine the dietary choline requirement are

diet composition (protein, fat and carbohydrate

levels), as well as gender, age, activity level and

energy intake of dogs.

caused by special astaxanthin pigmentation spots

that can change in size and intensity [12]. The ability to

change pigmentation is important to balance darker

coloration for UV protection, when at the surface,

versus higher transparency for camouflage. The green

can be seen in their digestive system and results

from algae they eat. Krill can eat up to 20% of their

body weight per day, but they also have the ability to

shrink when starving and can survive without food

for up to 200 days.

Adult krill can get up to 6 cm long and has blue light

emitting spots on the body speculated to play a

role in mating, swarm formation or camouflage from

above when the sun shines on them. Surprisingly, the

krill genome is about 12 times the size of the human

genome. Antarctic krill is harvested in the wild and

then cooked, dried and ground. Whole krill gives a

powder of brownish-orange color rich in proteins,

choline, omega-3 fatty acids and astaxanthin.

Figure 3: Antarctic krill (Euphausia superba)

ANTARCTIC KRILL

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Krill meal is made from Antarctic krill (Euphausia

superba), which is a crustacean related to shrimp (Fig.

3). But unlike shrimp that live on the ocean bottom,

krill aggregate in huge up to twenty-kilo-meter-long

swarms and move up and down the water column.

There are 85 different krill species around the world,

with Antarctic krill living in the Southern Ocean

around the frozen continent. Krill are transparent

with some red and green colorations. The red is

In humans, it was found that choline in the form of phospholipids is 12 times more efficient in raising blood choline

concentrations compared to choline chloride [10, 11].

While choline salt consumption in humans shows a 86% increase to a maximum plasma concentration after 30 minutes

returning to normal levels after four hours, phosphatidylcholine intake raises choline by 265% and takes 12 hours to decline [11].

Figure 5: Plasma choline levels

Figure 4: QRILL Pet ingredient

QRILL Pet is a functional

ingredient for pet food, rich

in phospholipid omega-3s,

choline, marine proteins and

astaxanthin. The choline found

in krill is all natural and in form

of phosphatidylcholine.

A previous study with krill meal was exploring it’s

benefits during an extreme endurance exercise, the

1600-km-long Iditarod dog sled race [13]. Iditarod

is perhaps the most extreme endurance exercise

performed by any domestic animal, and markers of

oxidative stress, inflammation and skeletal muscle

damage are known to be increased after the race [14].

The study reported that supplementation with krill

meal for 5 weeks before the race increased the

Omega-3 Index, which resulted in less inflammation

and muscle damage in the krill group in comparison

to a control group [13].

The latest study investigated if 8% dietary krill meal

inclusion for six weeks can increase the concen-

tration of choline and its metabolites in plasma of

Alaskan Huskies in comparison to a control group [15].

+52%

+18%

13,28

7,938,75

6,72

Baseline

Control QRILL Pet

End

KRILL MEAL RESEARCH

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The results demonstrated that a nutritional strategy,

such as the addition of phosphatidylcholine to the

diet, can help to significantly increase plasma choline

concentrations (Fig. 5), which correlated with changed

concentrations of various choline metabolites (Fig. 6).

Chol

ine

(µm

ol/L

)

BETAINE (μmol/L) DIMETHYLGLYCINE (μmol/L)

BaselineBetaine promotes muscle function and plasma volume expansion.

Dimethylglycine is involved in glucose metabolism.BaselineEnd End

429,634,1

230,1 14,8

METHIONINE (μmol/L) HOMOCYSTEINE (μmol/L)

BaselineMethionine is an important methyl donor. Homocysteine is a risk factor for heart disease.

BaselineEnd

114,7

8,3106,2

10,1

End

Figure 6: Change in choline metabolites in plasma

These results could be of importance in a long-lasting

race setting, when a drop in plasma choline is expected

as seen in humans [16]. As a consequence of lowered

free plasma choline concentrations, the generation of

acetylcholine (a neurotransmitter important for

muscle function) might be reduced and thereby

negatively affect athletic performance. Noteworthy,

from a performance perspective, is also the significant

increase in betaine in the krill group, which is thought

to promote muscle function and plasma volume

expansion as shown after betaine supplementation in

humans [17]. The study also found a significant reduction

of plasma total homocysteine. Homocysteine is known

to increase the risk of endothelial cell injury and

cardiovascular disease in humans by increasing reactive

oxygen species and altering lipoprotein metabolism [18]. A similar correlation has been identified in dogs [19]. Another metabolic derivative of choline that was

significantly increased in the krill meal supplemented

dogs was dimethylglycine, which was suggested to have

possible protective effects on glucose metabolism [20].

The results of the krill meal supplementation study are encouraging to ensure that sufficient choline is available for optimal cell and body system functions. This is of particular interest for dogs that perform long-distance races or have health ailments affecting the liver, brain and heart.

Additionally, the omega-3 fatty acids from krill mayfurther benefit the health of dogs by decreasing inflammation. Low-grade chronic inflammation is a characteristic of various diseases such as obesity, cardiovascular disease, arthritis, diabetes, fatty liver disease and some cancers.

Similarly, the astaxanthin present in krill meal has anti-inflammatory and antioxidant properties through its ability to scavenge free radicals, thereby counteracting oxidative stress and damage to proteins, lipids and DNA. Since Antarctic krill is protected from overfishing by CCAMLR and Aker BioMarine Antarctic AS has obtained the Marine Stewardship Certification to prove sustainable fishing, QRILL Pet is an attractive feed ingredient that ensures optimal health of pets in a sustainable manner.

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CONCLUSION

CHOLINE – AN ESSENTIAL NUTRIENT FOR DOGS

CHOLINE FORMS

HEALTH BENEFITS OF CHOLINE

SOURCES

HOW TO ENSURE YOUR DOG IS GETTING SUFFICIENT CHOLINE

Cholinechloride

Cholinebitartrate

Glycerophosphocholine

Citicoline

Phosphatidylcholine

REFERENCES

1. Burri L, Heggen K, Storsve AB (2019) Phosphatidylcholine from krill increases plasma choline and its metabolites in dogs, Veterinary World, 12(5): 671-676.

2. Wurtman, R.J., M.J. Hirsch, and J.H. Growdon, Lecithin consumption raises serum-free-choline levels. Lancet,1977. 2 (8028): p. 68-9.

increase of plasma choline

in dogs after 6 weeks on a

QRILL Pet diet

+52%

+18%

13,28

7,938,75

6,72

Baseline

Control QRILL Pet

End

52%

Choline from krill is a natural source of phosphatidylcholine (PC) . Another study has shown that consumption of choline in PC form also stays longer in the body. [2]

EGG

LIVER FISH

SOYBEAN

MEAT

WHEAT GERMKRILL

1700mgper kg dry matter

NRC recommendation

(2006) forall dogs

SOME OF THE MAJOR BENEFITS FOR HIGH PREFORMANCE DOGS

CARDIOVASCULARFUNCTION

COGNITIVEFUNCTION

OPTIMAL MUSCLEPERFORMANCE

DETOXIFICATION(METHYLATION)

IMPROVEDPERFORMANCE

LIVER

BRAIN & MEMORY

HEART

MUSCLE FUNCTION

REPRODUCTION

Recommended choline intake

WHY CHOLINE FROM KRILL?

The benefits of Phosphatidylcholine from krill in dog food

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[1]

IMPROVEDHEALTH

ABOUT THE AUTHOR

Lena Burri, Ph.D., has been involved in funda- mental research and is together with co-authorscredited with several original protein discoveries. She has published scientific articles in leading journals, and contributed book chapters, review articles and peer-reviewed manuscripts on many subjects, including omega-3 fatty acids. Lena earned her Master of Science from the University of Basel (Switzerland) and her Ph.D. at the Ludwig Institute for Cancer Research (Switzerland).

Her post-doctoral education included stays at Melbourne University (Australia), University of British Columbia (Canada) and University of Bergen (Norway). She now works as R&D Directorfor Animal Nutrition and Health for Aker BioMarine.

THOMAS WÆRNER & CO.

Thomas Wærner is a professional dog musher and a member of the QRILL Pet Mushing Team, the world´s first professional long-distance dog sled team. His dog team participated in the krill meal supplementation study described in this whitepaper.

In 2019, Thomas and his dog team won both of the biggest long-distance sled dog races in Norway, Finnmark race and Femund race. During these races the teams cover distances up to 1200 km. Thomas also  received the veterinarian award at the Finnmark race, which is handed out to themusher who demonstrated outstanding dog care and health. 

He owns and runs the Berserk kennel in Synnfjell, Norway. His previous achievements include the Finnmark race in 2013, 3rd place at the Femund race in 2013 and “Rookie of the year” at the Iditarod race in 2015.

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1. Food and Nutrition Board, I.o.M., Dietary Reference Intakes: Thiamin, Riboflavin, Niacin, Vitamin B-6, Vitamin B012, Pantothenic Acid, Biotin, and Choline. 1998, Washington, D.C.: National Academy of Sciences. p. 390-422.

2. Zeisel, S.H. and J.K. Blusztajn, Choline and human nutrition. Annu Rev Nutr, 1994. 14: p. 269-96.

3. Conlay, L.A., L.A. Sabounjian, and R.J. Wurtman, Exercise and neuromodulators: choline and acetylcholine in marathon runners. Int J Sports Med, 1992. 13 Suppl 1: p. S141-2.

4. Conlay, L.A., et al., Decreased plasma choline concentrations in marathon runners. N Engl J Med, 1986. 315(14): p. 892.

5. Marriott, B.M., Food Components to Enhance Performance: An evaluation of potential performance-enhancing food components for operational rations. 1994: National Academies Press.

6. Zeisel, S.H., T. Zola, and E. Pomfret, Effect of choline deficiency on S-adenosylmethionine and methionine concentrations in rat liver. Biochem J, 1989. 259(3): p. 725-729.

7. Best, C.H., J.M. Hershey, and M.E. Huntsman, The effect of lecithine on fat deposition in the liver of the normal rat. J Physiol, 1932. 75(1): p. 56-66.

8. Phleger, C.F., et al., Interannual and between species comparison of the lipids, fatty acids and sterols of Antarctic krill from the US AMLR Elephant Island survey area. Comp Biochem Physiol B Biochem Mol Biol, 2002. 131(4): p. 733-47.

9. Tou, J.C., J. Jaczynski, and Y.C. Chen, Krill for human consumption: nutritional value and potential health benefits. Nutr Rev, 2007. 65(2): p. 63-77.

10. Hirsch, M.J., J.H. Growdon, and R.J. Wurtman, Relations between dietary choline or lecithin intake, serum choline levels, and various metabolic indices. Metabolism, 1978. 27(8): p. 953-60.

11. Wurtman, R.J., M.J. Hirsch, and J.H. Growdon, Lecithin consumption raises serum-free-choline levels. Lancet, 1977. 2(8028): p. 68-9.

12. Auerswald, L., et al., Physiological and morphological colour change in Antarctic krill, Euphausia superba: a field study in the Lazarev Sea. J Exp Biol, 2008. 211(24): p. 3850-3858.

13. Burri, L., et al., Effects of dietary supplementation with krill meal on serum pro-inflammatory markers after the Iditarod sled dog race. Res Vet Sci, 2018. 121: p. 18-22.

14. Burr, J.R., et al., Serum biochemical values in sled dogs before and after competing in long-distance races. J Am Vet Med Assoc, 1997. 211(2): p. 175-9.

15. Burri, L., K. Heggen, and A. Storsve. Phosphatidylcholine from krill increases plasma choline and its metabolites in dogs, Vet World, 2019. 12(5): 671-676.

16. Jager, R., M. Purpura, and M. Kingsley, Phospholipids and sports performance. J Int Soc Sports Nutr, 2007. 4(1): p. 5.

17. Ismaeel, A., Effects of betaine supplementation on muscle strength and power: a systematic review. J Strength Cond Res, 2017. 31(8): p. 2338-2346.

18. Collaboration, H.S., Homocysteine and risk of ischemic heart disease and stroke: a meta-analysis. Jama, 2002. 288(16): p. 2015-2022.

19. Lee, C.-M., et al., Correlation between serum homocysteine concentration and severity of mitral valve disease in dogs. Am J Vet Res, 2017. 78(4): p. 440-446.

20. Magnusson, M., et al., Dimethylglycine deficiency and the development of diabetes. Diabetes, 2015. 64(8): p. 3010-3016.

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REFERENCES

ABOUT QRILL PET

QRILL Pet is a product of Aker BioMarine, a leading biotechnology company developing and supplying krill- derived products for consumer health and animal nutrition. When developing our functional marine ingredient for pets, we kept our focus on the needs of pets and pet food formulators. Aimed at keeping pets healthy, QRILL Pet delivers long-chain omega-3 fatty acids, marine proteins, choline and the antioxidant astaxanthin. The unique distinction of krill omega-3s is that they are mainly bound to phospholipids.

QRILL Pet is currently the only MSC (Marine Stewardship Council) certified krill meal in the world. The ingredient comes form one of the most sustainable fisheries in the world and can be traced back to the exact catch location of the krill.

Aker BioMarine Antarctic AS | Qrillpet.com | Akerbiomarine.comQRILL Pet is a trademark of Aker BioMarine Antarctic AS, Norway © 2019 Aker BioMarine. All rights reserved.